Patent Publication Number: US-2021189502-A1

Title: Methods for identifying cancer risk

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional application of U.S. application Ser. No. 12/625,240 filed Nov. 24, 2009, now issued as U.S. Pat. No. 10,927,415; which claims the benefit under 35 USC § 119(e) to U.S. Application Ser. No. 61/118,169 filed Nov. 26, 2008, now expired. The disclosure of each of the prior applications is considered part of and is incorporated by reference in the disclosure of this application. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with government support under Grant Nos. HG003233, GM083084 and CA054358 awarded by the National Institutes of Health. The government has certain rights in the invention. 
    
    
     BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present invention relates generally to differentially methylated regions (DMRs) in the genome outside CpG islands, and more specifically to methods for detecting the presence of or a risk for a hyperproliferative disorder by detecting an alteration in methylation status of such DMRs. 
     Background Information 
     Epigenetics is the study of non-sequence information of chromosome DNA during cell division and differentiation. The molecular basis of epigenetics is complex and involves modifications of the activation or inactivation of certain genes. Additionally, the chromatin proteins associated with DNA may be activated or silenced. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism&#39;s lifetime, but some epigenetic changes are inherited from one generation to the next. 
     One example of an epigenetic mechanism is DNA methylation (DNAm), a covalent modification of the nucleotide cytosine. In particular, it involves the addition of methyl groups to cytosine nucleotides in the DNA, to convert cytosine to 5-methylcytosine. DNA methylation plays an important role in determining whether some genes are expressed or not. Abnormal DNA methylation is one of the mechanisms underlying the changes observed with aging and development of many cancers. 
     Cancers have historically been linked to genetic changes such as DNA sequence mutations. Evidence now supports that a relatively large number of cancers originate, not from mutations, but from epigenetic changes such as inappropriate DNA methylation. In some cases, hypermethylation of DNA results the an inhibition of expression of critical genes, such as tumor suppressor genes or DNA repair genes, allowing cancers to develop. In other cases, hypomethylation of genes modulates expression, which contributes to the development of cancer. 
     Epigenetics has led to an epigenetic progenitor model of cancer that epigenetic alterations affecting tissue-specific division and differentiation are the predominant mechanism by which epigenetic changes cause cancer. In other words, it is believed that aberrant methylation patterns may play multiple roles in cancer, such as the silencing of tumor suppressor genes, and the over-expression of oncogenes. 
     Since the discovery of altered DNA methylation in human cancer, the focus has largely been on specific genes of interest and regions assumed to be important functionally, such as promoters and CpG islands, and there has not been a comprehensive genome-scale understanding of the relationship between DNA methylation loss and gain in cancer and in normal differentiation. 
     SUMMARY OF THE INVENTION 
     The present invention is based on the discovery that some tissue-specific or cancer-related alterations in DNA methylation occur not only in promoters or CpG islands, but in sequences up to 2 kb distant from such CpG islands (such sequences are termed “CpG island shores”). In accordance with this discovery, there are provided herein differentially methylated regions (DMRs) and methods of use thereof. 
     In one embodiment of the invention, there are provided methods of diagnosis including detecting a cell proliferative disorder. The methods involve comparing the methylation status of one or more nucleic acid sequences in a sample from a subject suspected of having the disorder, with the proviso that the one or more nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island, to the methylation status of the one or more nucleic acid sequences in a sample from a corresponding normal tissue or individual not having a cell proliferative disorder, wherein an alteration in methylation status is indicative of a cell proliferative disorder. 
     In certain embodiments, the cell proliferative disorder is cancer. In some embodiments, the nucleic acid sequence is within a gene; alternatively, the nucleic acid sequence is upstream or downstream of a gene. In particular embodiments, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the DPP6 gene, the MRPL36 gene, the MEST gene, the GATA-2 gene, the RARRES2 gene, and any combination thereof. In some embodiments the alteration in methylation status is hypomethylation; in other embodiments the alteration in methylation status is hypermethylation. In embodiments using more than one DMR, the alteration in methylation status of some may be hypomethylation, whereas others may be hypermethylation. 
     In another embodiment of the invention, there are provided methods of determining a clinical outcome. Such methods are accomplished by comparing the methylation status of one or more nucleic acid sequences in a sample from a subject prior to undergoing a therapeutic regimen for a disease or disorder, wherein the disease or disorder is associated with altered methylation of the one or more nucleic acid sequences, with the proviso that the one or more nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island, to the methylation status of the one or more nucleic acid sequences in a sample from the individual after the therapeutic regimen has been initiated, wherein change in methylation status is indicative a positive clinical outcome. In particular embodiments, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the DPP6 gene, the MRPL36 gene, the MEST gene, the GATA-2 gene, the RARRES2 gene, and any combination thereof. In some embodiments the change in methylation status is hypomethylation; in other embodiments the change in methylation status is hypermethylation. In embodiments using more than one DMR, the change in methylation status of some may be hypomethylation, whereas others may be hypermethylation. 
     In another embodiment of the invention, there are provided methods for providing a methylation map of a region of genomic DNA by performing comprehensive high-throughput array-based relative methylation (CHARM) analysis on, for example, a sample of labeled, digested genomic DNA. In some embodiments, the method may further include bisulfite pyrosequencing of the genomic DNA, for example. 
     In still another embodiment of the invention, there are provided methods of detecting a methylation status profile of the nucleic acid of a cancer cell from a tumor or biological sample. Such methods include hybridizing labeled and digested nucleic acid of a cancer cell from a tumor or biological sample to a DNA microarray comprising at least 100 nucleic acid sequences, with the proviso that the nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island and determining a pattern of methylation from the hybridizing of step a), thereby detecting a methylation profile. In particular embodiments, the method further includes comparing the methylation profile to a methylation profile from hybridization of the microarray with labeled and digested nucleic acid from control “normal” cells. In certain embodiments, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the DPP6 gene, the MRPL36 gene, the MEST gene, the GATA-2 gene, the RARRES2 gene, and any combination thereof. 
     In yet another embodiment of the present invention, there are provided methods for prognosis of a cancer in a subject known to have or suspected of having a cancer associated with altered methylation of one or more nucleic acid sequences. The method includes obtaining a tissue sample or biological sample containing nucleic acid from a subject; and assaying the methylation status of one or more nucleic acid sequences, with the proviso that the one or more nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island bodily fluid; wherein the presence of altered methylation in the sample from the subject, relative to a corresponding sample from a normal sample, is indicative that the subject is a good for therapy of cancer. In some embodiments, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the DPP6 gene, the MRPL36 gene, the MEST gene, the GATA-2 gene, the RARRES2 gene, and any combination thereof. 
     In another embodiment of the invention, there is provided a plurality of nucleic acid sequences, wherein the nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island, and wherein the nucleic acid sequences are differentially methylated in cancer. In some embodiments, the nucleic acid sequence are selected from the group consisting of the DMR sequences as set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the MRPL36 gene, the MEST gene, the GATA-2 gene, and the RARRES2 gene. In one aspect, the plurality is a microarray. 
     In another embodiment of the invention, there is provided a plurality of nucleic acid sequences, wherein the nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island, and wherein the nucleic acid sequences are differentially methylated in tissues derived from the three different embryonic lineages. In some embodiments, the plurality of nucleic acid sequences are selected from one or more of the sequences as set forth in  FIG. 5A ,  FIG. 5B , Tables 1, 2, 4, 7, 9, 10, 12-14, and 17. In one aspect, the plurality is a microarray. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  shows a plot of M value versus genomic location for brain, liver, and spleen (upper panel) and a plot of CpG density versus genomic location over the same region (lower panel) for a T-DMR located in a CpG island shore.  FIG. 1B  shows a plot of M value versus genomic location for brain, liver, spleen, normal colon, and colon tumor (upper panel) and a plot of CpG density versus genomic location over the same region (lower panel) for a C-DMR located in a CpG island shore that overlaps with a T-DMR. 
         FIG. 2  shows plots depicting the distribution of distance of T-DMRs and C-DMRs from CpG islands. 
         FIG. 3A  shows a quantile-quantile plot depicting the number of sites of hypomethylation and hypermethylation in colon cancer.  FIGS. 3B-3J  show box plots depicting the degree of DNA methylation of the indicated C-DMRs as measured by bisulfate pyrosequencing. 
         FIG. 4  shows a plot of differential gene expression versus differential methylation for brain and liver T-DMR. 
         FIGS. 5A-5B  show plots of the relative expression of hypermethylated T-DMR when treated with 5-aza-2′deoxycytidine ( FIG. 5A ) or in a double knockout of DNA methytransferase 1 and 3b ( FIG. 5B ). 
         FIG. 6  shows a clustering of human tissue samples using mouse T-DMRs. 
         FIGS. 7A and 7B  show a clustering of normal tissue samples using C-DMRs. 
         FIGS. 8A-8D  show box plots of average ΔM values over all DMRs compared to randomly chosen regions and unmethylated control regions matched for length.  FIG. 8E  shows box plots of ΔM for pairwise comparison.  FIG. 8F  shows box plots of the average inter-individual standard deviation of the ΔM value for normal mucosa and colon tumors. 
         FIG. 9  shows plots of M values for CHARM probes located within a CGI (left plot) and outside a CGI (right plot). 
         FIGS. 10A-10J  show representative plots of 10 T-DMRs. The upper panels are plots of M value versus genomic location for brain, liver, and spleen. The middle panels provide the location of CpG dinucleotides with tick marks on the x-axis. The lower panels provide gene annotation for the genomic region. 
         FIGS. 11A-11C  show plots of the distribution of distance of T-DMRs and C-DMRs from CpG islands using different FDR cutoff values (0.01, 0.05 and 0.10, for  FIGS. 11A, 11B and 11C , respectively. 
         FIGS. 12A-12J  show representative plots of 10 C-DMRs. The upper panels are plots of M value versus genomic location for brain, liver, spleen, normal colon, and colon cancer. The middle panels provide the location of CpG dinucleotides with black tick marks on the x-axis. The lower panels provide gene annotation for the genomic region. 
         FIGS. 13A-13E  show box plots of bisulfite pyrosequencing confirming the prevalence of 5 hypermethylated C-DMR shores in a large set of colon tumor and normal mucosa samples. Box-plots represent DNA methylation level measured using bisulfite pyrosequencing.  FIG. 13A , distal-less homeobox 5 (DLX5);  FIG. 13B , leucine rich repeat and fibronectin type III domain containing 5 (LRFN5);  FIG. 13C , homeobox A3 (HOXA3);  FIG. 13D , SLIT and NTRK-like family, member 1 (SLITRK1);  FIG. 13E , FEZ family zinc finger 2 (FEZF2), (n) equals the number of samples analyzed by pyrosequencing. 
         FIGS. 14A-14D  show box plots of bisulfite pyrosequencing confirming the prevalence of 4 hypomethylated C-DMR shores in a large set of colon tumor and normal mucosa samples. Box-plots represent DNA methylation level measured using bisulfite pyrosequencing.  FIG. 14A , transmembrane protein 14A (TMEM14A);  FIG. 14B , glutamate-rich 1 (ERICH1);  FIG. 14C , family with sequence similarity 70, member B (FAM70C);  FIG. 14D , prostate transmembrane protein, androgen induced 1 (TMEPAI), (n) equals the number of samples analyzed by pyrosequencing. 
         FIG. 15  shows a plot of log (base 2) ratios of colon tumor to normal expression against delta M values for colon tumor and normal DNAm. 
         FIG. 16  shows a plot of average delta M values stratified into T-DMRs, hypermethylated C-DMRs and hypomethylated C-DMRs. T-DMRs were further stratified according to brain versus liver, brain versus spleen, and liver versus spleen pair-wise comparisons. The box-plots represent absolute values of the delta Ms. 
         FIG. 17  shows a plot the average inter-individual standard deviation of the M-values for C-DMRs. The box-plots represent these values for normal colon mucosa and colon tumors. 
         FIG. 18A  shows a schematic overview of the PIP5K1A gene locus. C-DMR represents the genomic region that is hypomethylated in colon tumors as compared to normals.  FIG. 18B  shows a photograph of a gel in which the arrow indicates a 220 bp fragment present in 3 colon tumors but not normal mucosa from the same individual amplified by the Sp3 primer and the 5′ RACE anchor primer. 
         FIG. 19  shows an example of C-DMR that is not adjacent to a conventionally defined CpG island. The upper panel is a plot of M value versus genomic location for brain, liver, spleen, normal colon, colon tumor. The middle panel provides the location of CpG dinucleotides with tick marks on the x-axis. The lower panel provides gene annotation for the genomic region. 
         FIG. 20  shows a plot of hierarchical clustering. Columns represent individual samples, and rows represent regions corresponding to mouse T-DMRs. The heatmap displays M values, with some being more methylated and some being less methylated. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention is based on the discovery that some tissue-specific or cancer-related alterations in DNA methylation occur not only in promoters or CpG islands, but in sequences up to 2 kb distant (termed “CpG island shores”). In accordance with this discovery, there are provided herein tissue-specific differential methylated regions (T-DMRs) and cancer-related differential methylated regions (C-DMRs) and methods of use thereof. Accordingly, in one embodiment of the invention, there are provided methods of detecting a cell proliferative disorder. The methods involve comparing the methylation status of one or more nucleic acid sequences in a sample from a subject suspected of having the disorder, with the proviso that the one or more nucleic acid sequences are outside of a promoter region of a gene and outside of a CpG island, and wherein the nucleic acid sequence is up to about 2 kb in distance from a CpG island, to the methylation status of the one or more nucleic acid sequences in a sample from a corresponding normal tissue or individual not having a cell proliferative disorder, wherein an alteration in methylation status is indicative of a cell proliferative disorder. In some embodiments the alteration in methylation status is hypomethylation; in other embodiments the alteration in methylation status is hypermethylation. In embodiments using more than one DMR, the alteration in methylation status of some may be hypomethylation, whereas others may be hypermethylation. 
     In some embodiments methylation status is converted to an M value. As used herein an M value, can be a log ratio of intensities from total (Cy3) and McrBC-fractionated DNA (Cy5): positive and negative M values are quantitatively associated with methylated and unmethylated sites, respectively. 
     Hypomethylation of a DMR is present when there is a measurable decrease in methylation of the DMR. In some embodiments, a DMR can be determined to be hypomethylated when less than 50% of the methylation sites analyzed are not methylated. Hypermethylation of a DMR is present when there is a measurable increase in methylation of the DMR. In some embodiments, a DMR can be determined to be hypermethylated when more than 50% of the methylation sites analyzed are methylated. Methods for determining methylation states are provided herein and are known in the art. In some embodiments methylation status is converted to an M value. As used herein an M value, can be a log ratio of intensities from total (Cy3) and McrBC-fractionated DNA (Cy5): positive and negative M values are quantitatively associated with methylated and unmethylated sites, respectively. M values are calculated as described in the Examples. In some embodiments, M values which range from −0.5 to 0.5 represent unmethylated sites as defined by the control probes, and values from 0.5 to 1.5 represent baseline levels of methylation. 
     In particular embodiments, the one or more nucleic acid sequence is selected from the C-DMRs provided herein. In one aspect, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in Tables 1-4, 6, 7, 9, 11, 14-16, 18, the DPP6 gene, the MRPL36 gene, the MEST gene, the GATA-2 gene, the RARRES2 gene, and any combination thereof. In some embodiments, the nucleic acid sequence is within a gene; alternatively, the nucleic acid sequence is upstream or downstream of a gene. 
     In particular embodiments, the one or more nucleic acid sequence is selected from the T-DMRs provided herein. In one aspect, the one or more nucleic acid sequence is selected from the group consisting of the DMRs set forth in  FIG. 5A ,  FIG. 5B , Tables 1, 2, 4, 7, 9, 10, 12-14, and 17. Such T-DMRs may be used to distinguish between the tissue types representing the three embryonic lineages: endodermal, mesodermal, and ectodermal. 
     The biological sample can be virtually any biological sample, particularly a sample that contains RNA or DNA from the subject. The biological sample can be a tissue sample which contains about 1 to about 10,000,000, about 1000 to about 10,000,000, or about 1,000,000 to about 10,000,000 somatic cells. However, it is possible to obtain samples that contain smaller numbers of cells, even a single cell in embodiments that utilize an amplification protocol such as PCR. The sample need not contain any intact cells, so long as it contains sufficient biological material (e.g., protein or genetic material, such as RNA or DNA) to assess methylation status of the one or more DMRs. 
     In some embodiments, a biological or tissue sample can be drawn from any tissue that is susceptible to cancer. A biological or tissue sample may be obtained by surgery, biopsy, swab, stool, or other collection method. In some embodiments, the sample is derived from blood, plasma, serum, lymph, nerve-cell containing tissue, cerebrospinal fluid, biopsy material, tumor tissue, bone marrow, nervous tissue, skin, hair, tears, fetal material, amniocentesis material, uterine tissue, saliva, feces, or sperm. In particular embodiments, the biological sample for methods of the present invention can be, for example, a sample from colorectal tissue, or in certain embodiments, can be a blood sample, or a fraction of a blood sample such as a peripheral blood lymphocyte (PBL) fraction. Methods for isolating PBLs from whole blood are well known in the art. In addition, it is possible to use a blood sample and enrich the small amount of circulating cells from a tissue of interest, e.g., colon, breast, lung, prostate, head and neck, etc. using a method known in the art. 
     As disclosed above, the biological sample can be a blood sample. The blood sample can be obtained using methods known in the art, such as finger prick or phlebotomy. Suitably, the blood sample is approximately 0.1 to 20 ml, or alternatively approximately 1 to 15 ml with the volume of blood being approximately 10 ml. 
     Accordingly, in one embodiment, the identified cancer risk is for colorectal cancer, and the biological sample is a tissue sample obtained from the colon, blood, or a stool sample. In another embodiment, the identified cancer risk is for stomach cancer or esophageal cancer, and the tissue may be obtained by endoscopic biopsy or aspiration, or stool sample or saliva sample. In another embodiment, the identified cancer risk is esophageal cancer, and the tissue is obtained by endoscopic biopsy, aspiration, or oral or saliva sample. In another embodiment, the identified cancer risk is leukemia/lymphoma and the tissue sample is blood. 
     In the present invention, the subject is typically a human but also can be any mammal, including, but not limited to, a dog, cat, rabbit, cow, bird, rat, horse, pig, or monkey. 
     As mentioned above, for certain embodiments of the present invention, the method is performed as part of a regular checkup. Therefore, for these methods the subject has not been diagnosed with cancer, and typically for these present embodiments it is not known that a subject has a hyperproliferative disorder, such as a cancer. 
     Methods of the present invention identify a risk of developing cancer for a subject. A cancer can include, but is not limited to, colorectal cancer, esophageal cancer, stomach cancer, leukemia/lymphoma, lung cancer, prostate cancer, uterine cancer, breast cancer, skin cancer, endocrine cancer, urinary cancer, pancreas cancer, other gastrointestinal cancer, ovarian cancer, cervical cancer, head cancer, neck cancer, and adenomas. In one aspect, the cancer is colorectal cancer. 
     A hyperproliferative disorder includes, but is not limited to, neoplasms located in the following: abdomen, bone, breast, digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and peripheral), lymphatic system, pelvic, skin, soft tissue, spleen, thoracic, and urogenital. In certain embodiments, the hyperproliferative disorder is a cancer. In one aspect, the cancer is colorectal cancer. 
     In another embodiment, the present invention provides a method for managing health of a subject. The method includes performing the method for identifying an increased risk of developing cancer discussed above and performing a traditional cancer detection method. For example a traditional cancer detection method can be performed if the method for identifying cancer risk indicates that the subject is at an increased risk for developing cancer. Many traditional cancer detection methods are known and can be included in this aspect of the invention. The traditional cancer detection method can include, for example, one or more of chest X-ray, carcinoembryonic antigen (CEA) level determination, colorectal examination, endoscopic examination, MRI, CAT scanning, or other imaging such as gallium scanning, and barium imaging, and sigmoidoscopy/colonoscopy, a breast exam, or a prostate specific antigen (PSA) assay. 
     Numerous methods for analyzing methylation status of a gene are known in the art and can be used in the methods of the present invention to identify either hypomethylation or hypermethylation of the one or more DMRs. In some embodiments, the determining of methylation status is performed by one or more techniques selected from the group consisting of a nucleic acid amplification, polymerase chain reaction (PCR), methylation specific PCR, bisulfite pyrosequenceing, single-strand conformation polymorphism (SSCP) analysis, restriction analysis, microarray technology, and proteomics. As illustrated in the Examples herein, analysis of methylation can be performed by bisulfite genomic sequencing. Bisulfite treatment modifies DNA converting unmethylated, but not methylated, cytosines to uracil. Bisulfite treatment can be carried out using the METHYLEASY bisulfite modification kit (Human Genetic Signatures). 
     In some embodiments, bisulfite pyrosequencing, which is a sequencing-based analysis of DNA methylation that quantitatively measures multiple, consecutive CpG sites individually with high accuracy and reproducibility, may be used. Exemplary primers for such analysis are set forth in Table 8. 
     It will be recognized that depending on the site bound by the primer and the direction of extension from a primer, that the primers listed above can be used in different pairs. Furthermore, it will be recognized that additional primers can be identified within the DMRs, especially primers that allow analysis of the same methylation sites as those analyzed with primers that correspond to the primers disclosed herein. 
     Altered methylation can be identified by identifying a detectable difference in methylation. For example, hypomethylation can be determined by identifying whether after bisulfite treatment a uracil or a cytosine is present a particular location. If uracil is present after bisulfite treatment, then the residue is unmethylated. Hypomethylation is present when there is a measurable decrease in methylation. 
     In an alternative embodiment, the method for analyzing methylation of the DMR can include amplification using a primer pair specific for methylated residues within a DMR. In these embodiments, selective hybridization or binding of at least one of the primers is dependent on the methylation state of the target DNA sequence (Herman et al.,  Proc. Natl. Acad. Sci. USA,  93:9821 (1996)). For example, the amplification reaction can be preceded by bisulfite treatment, and the primers can selectively hybridize to target sequences in a manner that is dependent on bisulfite treatment. For example, one primer can selectively bind to a target sequence only when one or more base of the target sequence is altered by bisulfite treatment, thereby being specific for a methylated target sequence. 
     Other methods are known in the art for determining methylation status of a DMR, including, but not limited to, array-based methylation analysis and Southern blot analysis. 
     Methods using an amplification reaction, for example methods above for detecting hypomethylation or hyprmethylation of one or more DMRs, can utilize a real-time detection amplification procedure. For example, the method can utilize molecular beacon technology (Tyagi S., et al.,  Nature Biotechnology,  14: 303 (1996)) or Taqman™ technology (Holland, P. M., et al., Proc.  Natl. Acad. Sci. USA,  88:7276 (1991)). 
     Also methyl light (Trinh B N, Long T I, Laird P W. DNA methylation analysis by MethyLight technology, Methods, 25(4):456-62 (2001), incorporated herein in its entirety by reference), Methyl Heavy (Epigenomics, Berlin, Germany), or SNuPE (single nucleotide primer extension) (See, e.g., Watson D., et al.,  Genet Res.  75(3):269-74 (2000)). Can be used in the methods of the present invention related to identifying altered methylation of DMRs. 
     As used herein, the term “selective hybridization” or “selectively hybridize” refers to hybridization under moderately stringent or highly stringent physiological conditions, which can distinguish related nucleotide sequences from unrelated nucleotide sequences. 
     As known in the art, in nucleic acid hybridization reactions, the conditions used to achieve a particular level of stringency will vary, depending on the nature of the nucleic acids being hybridized. For example, the length, degree of complementarity, nucleotide sequence composition (for example, relative GC:AT content), and nucleic acid type, i.e., whether the oligonucleotide or the target nucleic acid sequence is DNA or RNA, can be considered in selecting hybridization conditions. An additional consideration is whether one of the nucleic acids is immobilized, for example, on a filter. Methods for selecting appropriate stringency conditions can be determined empirically or estimated using various formulas, and are well known in the art (see, for example, Sambrook et al., supra, 1989). 
     An example of progressively higher stringency conditions is as follows: 2×SSC/0.1% SDS at about room temperature (hybridization conditions); 0.2×SSC/0.1% SDS at about room temperature (low stringency conditions); 0.2×SSC/0.1% SDS at about 42° C. (moderate stringency conditions); and 0.1×SSC at about 68° C. (high stringency conditions). Washing can be carried out using only one of these conditions, for example, high stringency conditions, or each of the conditions can be used, for example, for 10 to 15 minutes each, in the order listed above, repeating any or all of the steps listed. 
     The degree of methylation in the DNA associated with the DMRs being assessed, may be measured by fluorescent in situ hybridization (FISH) by means of probes which identify and differentiate between genomic DNAs, associated with the DMRs being assessed, which exhibit different degrees of DNA methylation. FISH is described in the Human chromosomes: principles and techniques (Editors, Ram S. Verma, Arvind Babu Verma, Ram S.) 2nd ed., New York: McGraw-Hill, 1995, and de Capoa A., Di Leandro M., Grappelli C., Menendez F., Poggesi I., Giancotti P., Marotta, M. R., Spano A., Rocchi M., Archidiacono N., Niveleau A. Computer-assisted analysis of methylation status of individual interphase nuclei in human cultured cells.  Cytometry.  31:85-92, 1998 which is incorporated herein by reference. In this case, the biological sample will typically be any which contains sufficient whole cells or nuclei to perform short term culture. Usually, the sample will be a tissue sample that contains 10 to 10,000, or, for example, 100 to 10,000, whole somatic cells. 
     Additionally, as mentioned above, methyl light, methyl heavy, and array-based methylation analysis can be performed, by using bisulfate treated DNA that is then PCR-amplified, against microarrays of oligonucleotide target sequences with the various forms corresponding to unmethylated and methylated DNA. 
     The term “nucleic acid molecule” is used broadly herein to mean a sequence of deoxyribonucleotides or ribonucleotides that are linked together by a phosphodiester bond. As such, the term “nucleic acid molecule” is meant to include DNA and RNA, which can be single stranded or double stranded, as well as DNA/RNA hybrids. Furthermore, the term “nucleic acid molecule” as used herein includes naturally occurring nucleic acid molecules, which can be isolated from a cell, as well as synthetic molecules, which can be prepared, for example, by methods of chemical synthesis or by enzymatic methods such as by the polymerase chain reaction (PCR), and, in various embodiments, can contain nucleotide analogs or a backbone bond other than a phosphodiester bond. 
     The terms “polynucleotide” and “oligonucleotide” also are used herein to refer to nucleic acid molecules. Although no specific distinction from each other or from “nucleic acid molecule” is intended by the use of these terms, the term “polynucleotide” is used generally in reference to a nucleic acid molecule that encodes a polypeptide, or a peptide portion thereof, whereas the term “oligonucleotide” is used generally in reference to a nucleotide sequence useful as a probe, a PCR primer, an antisense molecule, or the like. Of course, it will be recognized that an “oligonucleotide” also can encode a peptide. As such, the different terms are used primarily for convenience of discussion. 
     A polynucleotide or oligonucleotide comprising naturally occurring nucleotides and phosphodiester bonds can be chemically synthesized or can be produced using recombinant DNA methods, using an appropriate polynucleotide as a template. In comparison, a polynucleotide comprising nucleotide analogs or covalent bonds other than phosphodiester bonds generally will be chemically synthesized, although an enzyme such as T7 polymerase can incorporate certain types of nucleotide analogs into a polynucleotide and, therefore, can be used to produce such a polynucleotide recombinantly from an appropriate template. 
     In another aspect, the present invention includes kits that are useful for carrying out the methods of the present invention. The components contained in the kit depend on a number of factors, including: the particular analytical technique used to detect methylation or measure the degree of methylation or a change in methylation, and the one or more DMRs is being assayed for methylation status. 
     Accordingly, the present invention provides a kit for determining a methylation status of one or more differentially methylated region (DMR) of the invention. In some embodiments, the one or more T-DMRs are selected from one or more of the sequences as set forth in Tables 1-4, 6, 7, 9, 11, 14-16, the MRPL36 gene, the MEST gene, the GATA-2 gene, and the RARRES2 gene. In another embodiment, the one or more T-DMRs are selected from one or more of the sequences as set forth in  FIG. 5A ,  FIG. 5B , Tables 1, 2, 4, 7, 9, 10, 12-14, and 17. The kit includes an oligonucleotide probe, primer, or primer pair, or combination thereof for carrying out a method for detecting hypomethylation, as discussed above. For example, the probe, primer, or primer pair, can be capable of selectively hybridizing to the DMR either with or without prior bisulfite treatment of the DMR. The kit can further include one or more detectable labels. 
     The kit can also include a plurality of oligonucleotide probes, primers, or primer pairs, or combinations thereof, capable of selectively hybridizing to the DMR with or without prior bisulfite treatment of the DMR. The kit can include an oligonucleotide primer pair that hybridizes under stringent conditions to all or a portion of the DMR only after bisulfite treatment. In one aspect, the kit can provide reagents for bisulfite pyrosequencing including one or more primer pairs set forth in Table 8. The kit can include instructions on using kit components to identify, for example, the presence of cancer or an increased risk of developing cancer. 
     The studies provided herein focused on three key questions. First, where are DNA methylation changes that distinguish tissue types? Taking a comprehensive genome-wide approach, three normal tissue types representing the three embryonic lineages—liver (endodermal), spleen (mesodermal) and brain (ectodermal)—obtained from five autopsies were examined. A difference from previous methylation studies of tissues, aside from the genome-wide design herein, is that in the present studies, tissues were obtained from the same individual, thus controlling for potential interindividual variability. Second, where are DNAm alterations in cancer, and what is the balance between hypomethylation and hypermethylation? For this purpose, 13 colorectal cancers and matched normal mucosa from the subjects were examined. Third, what is the functional role of these methylation changes? To this end, a comparative epigenomics study of tissue methylation in the mouse, as well as gene expression analyses were carried out. 
     To examine DNAm on a genome-wide scale, comprehensive high-throughput array-based relative methylation (CHARM) analysis, which is a microarray-based method agnostic to preconceptions about DNAm, including location relative to genes and CpG content was carried out. The resulting quantitative measurements of DNAm, denoted with M, are log ratios of intensities from total (Cy3) and McrBC-fractionated DNA (Cy5): positive and negative M values are quantitatively associated with methylated and unmethylated sites, respectively. For each sample, ˜4.6 million CpG sites across the genome were analyzed using a custom-designed NimbleGen HD2 microarray, including all of the classically defined CpG islands as well as all nonrepetitive lower CpG density genomic regions of the genome. 4,500 control probes were included to standardize these M values so that unmethylated regions were associated, on average, with values of 0. CHARM is 100% specific at 90% sensitivity for known methylation marks identified by other methods (for example, in promoters) and includes the approximately half of the genome not identified by conventional region preselection. The CHARM results were also extensively corroborated by quantitative bisulfite pyrosequencing analysis. 
     Provided herein is a genome-wide analysis of DNA methylation addressing variation among normal tissue types, variation between cancer and normal, and variation between human and mouse, revealing several surprising relationships among these three types of epigenetic variation, supported by extensive bisulfite pyrosequencing and functional analysis. First, most tissue-specific DNAm was found to occur, not at CpG islands, but at CpG island shores (sequences up to 2 kb distant from CpG islands). The identification of these regions opens the door to functional studies, such as those investigating the mechanism of targeting DNAm to these regions and the role of differential methylation of shores. Supporting a functional role for shores, gene expression was closely linked to T-DMR and C-DMR methylation, particularly for switches from ‘none’ to ‘some’ methylation. The relationship between shore methylation and gene expression was confirmed by 5-aza-2′-deoxycytidine and DNA methyltransferase knockout experiments altering expression of the same genes. Another mechanism for shores supported by this study is regulation of alternative transcripts, supported by mapping and RACE experiments. 
     Although 76% of T-DMRs identified herein were in CpG island shores, at least for the three tissues examined here, 24% were not adjacent to conventionally defined CpG islands. However, many of these regions were nevertheless shores of CpG-enriched sequences (for an example, see  FIGS. 13A-13E ). We are currently developing a novel algorithm for CpG island definition based on hidden Markov modeling that will likely increase the fraction of T-DMRs in CpG island shores. The ‘CpG clusters’ recently identified (Glass et al., Nucleic Acids Res 35:6798-6807, 2007) are not CpG island shores (only 4% of shore DMRs map to them), although the shores of these clusters, like the shores of CpG islands, are enriched for DMRs. Note that the variation in DNAm is still not within the dense CpG regions as defined by any of these definitions but in CpG shores. 
     A second key finding of the studies provided herein is that T-DMRs are highly conserved between human and mouse, and the methylation itself is sufficiently conserved to completely discriminate tissue types regardless of species of origin. This was true even for T-DMRs located &gt;2 kb from transcriptional start sites. The incorporation of epigenetic data, such as DNAm, in evolutionary studies as done here, should greatly enhance the identification of conserved elements that regulate differentiation. Greater DNAm heterogeneity was found in human than in mouse (at least in an inbred strain), even for DMRs located &gt;2 kb from a gene promoter. While not wishing to be bound to any particular theory, this result suggests that the conservation of DNAm between human and mouse may have a strong genetic basis, consistent with a greater degree of tissue DNAm homogeneity in the inbred mouse strain. 
     A third key finding of the studies provided herein is that most cancer-related changes in DNAm, that is, C-DMRs, at least for colon cancer, correspond to T-DMRs, and that these changes are similarly divided between hypomethylation and hypermethylation and also involve CpG island shores. Thus, epigenetic changes in cancer largely involve the same DMRs as epigenetic changes in normal differentiation. These results have important implications for studies such as the Cancer Genome Atlas, in that most altered DNA methylation in cancer does not involve CpG islands, and thus these studies would benefit from analysis of CpG island shores. Similarly, high-throughput sequencing efforts based on reduced representation analysis of CpG islands per se are unlikely to identify most DNAm variation in normal tissues or in cancer. 
     Finally, GO annotation analysis suggests that DNAm changes in cancer reflect development and pluripotency-associated genes, and differentiated cellular functions for lineages other than the colon. These data are consistent with the epigenetic progenitor model of cancer (Feinberg et al., Nat Rev Genet 7:21-33, 2006), which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer. The genes identified in the studies provided herein will themselves be of considerable interest for further study, as will be the potential regulatory regions that did not lie in close proximity to annotated genes. 
     The following example is provided to further illustrate the advantages and features of the present invention, but are not intended to limit the scope of the invention. While they are typical of those that might be used, other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used. 
     Example 
     The Human Colon Cancer Methylome Shows Similar Hypo- and Hypermethylation at Conserved Tissue-Specific CpG Island Shores 
     It has been shown that alterations in DNA methylation (DNAm) occur in cancer, including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes. However, most studies of cancer methylation have assumed that functionally important DNAm will occur in promoters, and that most DNAm changes in cancer occur in CpG islands. This example illustrates that most methylation alterations in colon cancer occur not in promoters, and also not in CpG islands, but in sequences up to 2 kb distant, which are termed herein ‘CpG island shores’. CpG island shore methylation was strongly related to gene expression, and it was highly conserved in mouse, discriminating tissue types regardless of species of origin. There was a notable overlap (45-65%) of the locations of colon cancer-related methylation changes with those that distinguished normal tissues, with hypermethylation enriched closer to the associated CpG islands, and hypomethylation enriched further from the associated CpG island and resembling that of non-colon normal tissues. Thus, methylation changes in cancer are at sites that vary normally in tissue differentiation, consistent with the epigenetic progenitor model of cancer, which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer. 
     Samples. Snap-frozen colon tumors and dissected normal mucosa were obtained from the same subjects. For the tissue studies, human postmortem brain, liver and spleen tissues, from the same individual, were obtained. 
     Genomic DNA isolation and McrBC fractionation. Genomic DNA isolation was carried out using the MasterPure DNA purification kit (Epicentre) as recommended by the manufacturer. For each sample, 5 μg of genomic DNA was digested, fractionated, labeled and hybridized to a CHARM microarray (Irizarrry et al., Genome Res 18:771-9, 2008). 
     CHARM microarray design. CHARM microarrays were prepared as previously described (Irizarrry et al., Genome Res 18:771-9, 2008) and additionally included a set of 4,500 probes, totaling 148,500 base pairs across 30 genomic regions as controls. As these control probes represent genomic regions without CpG sites and hence cannot be methylated, they were used to normalize and standardize array data. The observed M values were standardized so that the average in the control regions was 0. Therefore, M values of 0 for other probes on the array were associated with no methylation. 
     CHARM DNA methylation analysis. McrBC fractionation was conducted followed by CHARM array hybridization for all human tissue samples as previously described (Irizarrry et al., Genome Res 18:771-9, 2008). For each probe, average M values were computed across the five samples in each tissue type. Differential methylation was quantified for each pairwise tissue comparison by the difference of averaged M values (ΔM). Replicates were used to estimate probe-specific s.d., which provided standard errors (s.e.m.) for ΔM. z scores (ΔM/s.e.m. (:ΔM)) were calculated and grouped contiguous statistically significant values into regions. Because millions of z scores were examined, statistical confidence calculation needed to account for multiple comparisons. Therefore false discovery rates (FDR) were computed and a list with an FDR of 5% was reported. Statistical significance of the regions was assessed as described below. C-DMRs were determined using the same procedure described above with the following exception: because greater heterogeneity was observed in the cancer samples ( FIG. 8F ), ΔM was not divided by the standard errors, as this would penalize regions of highly variable M values. For all expression microarray analysis, RMA was used for processing and then the samples were averaged in each tissue, and the difference (equivalent to average log ratio) computed. Mouse T-DMRs were determined using the same statistical procedures as described above for the T-DMRs and were then mapped to the human genome using the UCSC liftOver tool. To correct for possible ‘array’ effects, each T-DMR was standardized by subtracting the mean of M across all samples within a species and divided by s.d. across all samples within a species. A list of all mouse T-DMRs is provided in Table 17. Overlap of C-DMRs with T-DMRs was determined by adding the number of regions. 
     Statistical significance of DMRs. Contiguous regions composed of probes with z scores associated with P values smaller than 0.001 were grouped into regions. The area of each region (length multiplied by ΔM) was used to define statistical significance. A permutation test was used to form a null distribution for these areas and the empirical Bayes approach described. The effect of fragment length on M values observed using CHARM was tested by computing the expected DNA fragment size based on McrBC recognition sites. Next, the ΔM values were stratified for each probe, from the colon tumor and normal mucosa comparison, by fragment size. The results showed no relationship between fragment size and ΔM. 
     Bisulfite pyrosequencing. Isolation of genomic DNA for all bisulfite pyrosequencing validation was done using the MasterPure DNA purification kit (Epicentre) as recommended by the manufacturer. For validation of shore regions, 1 μg of genomic DNA from each sample was bisulfite-treated using an EpiTect kit (Qiagen) according to the manufacturer&#39;s specifications. Converted genomic DNA was PCR-amplified using unbiased nested primers and carried out quantitative pyrosequencing using a PSQ HS96 (Biotage) to determine percentage methylation at each CpG site. Primer sequences and annealing temperatures are provided in Table 8. For bisulfite pyrosequencing of C-DMRs in 34-65 colon tumor and 30-61 normal mucosa samples, 500 ng of genomic DNA was bisulfite-treated using the EZ-96 DNA Methylation Gold kit (Zymo Research) as specified by the manufacturer. Converted genomic DNA was PCR-amplified using unbiased nested primers followed by pyrosequencing using a PSQ HS96 (Biotage). Bisulfite pyrosequencing was done as previously described (Tost et al., Nat Protocols 2:2265-75, 2007). Percent methylation was determined at each CpG site using the Q-CpG methylation software (Biotage). Table 6 provides the genomic location of CpG sites measured in the CpG shore and associated CpG island bisulfite pyrosequencing assays. Genomic coordinates for all CpG sites measured in the set of −50 colon tumor and normal samples are provided in Methods online. The genomic coordinates for CpG sites measured in colon tumor and normal samples representing DLXSC, ERICH1, FAM70B, SLITRK1, FEZF2, LRFN5, TMEM14A, TMEPAI, and HOXA3 are chr7:96493826,96493847; chr8: 847868,847870; chr13:113615615; chr13:83352935; chr3:62335457,62335482,62335504; chr14:41148241,41148246,41148252; chr6:52638087; chr20:55707264; and chr7:27130446,27130448,27130450, respectively. Primer sequences and annealing temperatures for all bisulfite pyrosequencing reactions are provided in Table 7. 
     Total RNA isolation. Total RNA was isolated for Affymetrix microarray analysis from all human tissues using the RNEASY Mini kit (Qiagen) as specified by the manufacturer. All samples were DNase treated using the on-column DNase digestion kit (Qiagen) as recommended. Total RNA concentration was measured and RNA quality was determined by using an RNA 6000 Nano Lab chip kit and running the chip on a 2100 Bioanalyzer (Agilent). 
     Affymetrix microarray expression analysis. Genome-wide transcriptional analysis was done on a total of five liver and five brain samples from the same individuals using Affymetrix U133A GeneChip microarrays. The raw microarray gene expression data was obtained for the brain and liver tissue from The Stanley Medical Research Institute (SMRI) online genomics database (see URLs section below). The five individuals selected were unaffected controls from the SMRI Array collection. Genome-wide transcriptional profiling was also carried out on four colon tumor and four matched normal mucosa using Affymetrix U133 Plus 2.0 microarrays. One microgram of high-quality total RNA was amplified, labeled and hybridized according to the manufacturer&#39;s (Affymetrix) specifications and data was normalized as previously described (Irizarry et al. Biostatistics 4:249-64, 2003; and Bolstad et al., Bioinformatics 19:185-93, 1999). 
     Quantitative real-time PCR. Quantitative real time PCR was performed on high quality total RNA samples, determined using Agilent Bioanalyzer and RNA Nano 6000 chips, using pre-optimized Taqman assays (Applied Biosystems). A summary of assay identification numbers can be found in Table 9. Total RNA was prepared for quantitative real-time PCR using the Trizol method (Invitrogen) for FZD3, RBM38, NDN and SEMA3C and the RNEASY mini kit (Qiagen) was used to isolate total RNA for ZNF804A, CHRM2 and NQO1. cDNA was prepared for quantitative real-time PCR using the QUANTITECT RT kit (Qiagen) with Turbo DNase to eliminate genomic DNA. TaqMan assays (Applied Biosystems) were used to determine relative gene expression and analyzed experiments on a 7900HT detection system. Taqman assays (Applied Biosystems) were used to determine relative gene expression and experiments were analyzed on a 7900HT detection system. Human ACTB was used as an endogenous control. Relative expression differences were calculated using the AACt method (Livak and Schmittgen, Methods 25:402-8, 2001). 
     5′ RACE PCR. 5′ RACE experiments were done using a second generation RACE kit (Roche Applied Science) as specified by the manufacturer&#39;s protocol. RACE PCR products were directly sequenced with 3100 Genetic Analyzer (AB Applied Biosystems). The sequences for our gene specific primers are: PIP5K1A cDNA synthesis (PIP5K1A-Sp1): TCCTGAGGAATCAACACTTC (SEQ ID NO:1); first round PIP5K1A primer (PIP5K1A-Sp2): CAGATGCCATGGGTCTCTTG (SEQ ID NO:2); second round PIP5K1A primer (PIP5K1A-Sp3): ACGTCGAGCCGGCTCCTGGA (SEQ ID NO:3). 
     Soft agar assay for colony growth. HeLa and HCT116 cell lines were purchased from American Type Culture Collection (ATCC) and cultured using media and conditions recommended by the supplier. Cells were transfected with sequence verified full-length cDNAs of NQO1, ZNF804A, and CHRM2, and empty expression plasmid constructs obtained from Open Biosystems (Huntsville, Ala.) using Fugene (Roche) following supplied protocols. After 48 hours cells were harvested by trypsin treatment and resuspended in quadruplets at 5000 cells/35 mm well in 0.35% agar overlaid over 0.5% agar. The culture media contained 1×DMEM, 10% fetal bovine serum, 100 units/ml penicillin/streptomycin. Cells were incubated in a humidified CO 2  incubator (37° C., 5% CO 2 ) for 17 days followed by staining with 0.005% Crystal Violet for 2 hours. Colonies were counted under a light microscope. 
     GO annotation. GO annotation was analyzed using the Bioconductor Gostats package to find enriched categories (P&lt;0.01). 
     URLs. Complete set of T-DMR plots is on the internet at rafalab.jhsph.edu/t-dmr3000.pdf; complete set of C DMR plots is on the internet at rafalab.jhsph.edu/c-dmr-all.pdf. The Stanley Medical Research Institute (SMRI) online genomics database is available at stanleygenomics.org. 
     Accession codes. NCBI GEO: Gene expression microarray data was submitted under accession number GSE13471. 
     Most tissue-specific DNAm occurs in ‘CpG island shores.’ Because CHARM is not biased for CpG island or promoter sequences, objective data on tissue-specific methylation could be obtained. 16,379 tissue differential methylation regions (T-DMRs), defined as regions with M values for one tissue consistently different than that for the others at a false discovery rate (FDR) of 5% (see Methods) were identified. The median size of a T-DMR was 255 bp. Previous studies of tissue- or cancer-specific DNAm have focused on promoters and/or CpG islands, which have been defined as regions with a GC fraction greater than 0.5 and an observed-to-expected ratio of CpG greater than 0.6 (Feinberg, A. P. &amp; Tycko, B., Nat. Rev. Cancer 4, 143-153, 2004; and Gardiner-Garden, M. &amp; Frommer, M., J. Mol. Biol. 196, 261-282, 1987). It has previously been reported that the degree of differences in DNAm of promoters in somatic cells is relatively low in conventionally defined CpG islands and higher at promoters with intermediate CpG density. Two recent studies identified a relatively small fraction, 4-8%, of CpG islands with tissue-specific methylation. It was also found herein that DNAm variation is uncommon in CpG islands ( FIG. 9 ). 
     The genome-wide approach of CHARM also enabled the finding of an unexpected physical relationship between CpG islands and DNAm variation, namely that 76% of T-DMRs were located within 2 kb of islands in regions denoted herein as ‘CpG island shores.’ For example, for the T-DMR in the PRTFDC1 gene, which encodes a brain-specific phosphoribosyltransferase that is relatively hypomethylated in the brain, the spreading of M values among the tissues begins ˜200 bp from the CpG island and at a point where the CpG density associated with the island has fallen to 1/10 the density in the island itself ( FIGS. 1A-1B ). The association of T-DMRs with CpG island shores was not due to an arbitrary definition of CpG islands but to a true association of these DNAm differences near but not in the regions of dense CpG content (Table 10 describes some of the identified T-DMR regions. The complete set of T-DMRs is available on the Nature Genetics website (nature. com/naturegenetics) see “Supplementary Data 1” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186). Plots similar to those in  FIGS. 1A-1B  for 10 of the T-DMRs are provided in  FIGS. 10A-10J ; the complete set of T-DMRs plots, ordered by statistical significance, are available online at rafalab.jhsph.edu/t-dmr3000.pdf). The distribution of T-DMRs by distance from the respective islands showed that DNAm variation is distributed over a ˜2 kb shore, and that although CpG islands are enriched on the arrays, because of their high CpG content (33% of CHARM probes are in islands), only 6% of T-DMRs are in islands, compared to 76% in shores; an additional 18% of T-DMRs were located greater than 2 kb from the respective islands ( FIG. 2 ). The localization of T-DMRs also occurred largely outside of promoters (96%), as CpG islands are localized primarily within promoters. Furthermore, more than half (52%) of T-DMRs were greater than 2 kb from the nearest annotated gene. The distribution of the distance to islands remained essentially unchanged when we used FDR cutoffs of 0.01, 0.05 and 0.10. 
     The array-based result that the differential methylation was in CpG island shores rather than in the associated islands was confirmed by carrying out bisulfite pyrosequencing analysis on over 100 CpG sites in the islands and shores associated with four genes, three T-DMRs and one cancer differential methylation region. At all 101 sites, the DMR was confirmed to lie within the shore rather than the island (Table 1). For example, PCDH9, which encodes a brain-specific protocadherin, was relatively hypomethylated in the brain at all 6 sites examined in the CpG island shore but unmethylated in both brain and spleen at all 18 sites examined in the associated island (Table 1). Differential methylation of an additional four CpG island shores was also confirmed by bisulfite pyrosequencing of 39 total CpG sites, and all showed statistically significant differences in DNAm (P&lt;0.05) (Table 2). These data verify the sensitivity of CHARM for detecting subtle differences in DNAm. Furthermore, they confirm that most normal differential methylation takes place at CpG island shores. 
       FIGS. 1A-1B  illustrate that most tissue-specific differential DNA methylation was located at CpG island shores. ( FIG. 1A ) An example of a T-DMR located at a CpG island shore in the PRTFDC1 gene. The upper panel is a plot of M value versus genomic location for brain, liver and spleen. Each point represents the methylation level of an individual sample for a given probe. The curve represents averaged smoothed M values, described in detail in the Methods. Because of the scale and standardization used, M values that range from −0.5 to 0.5 represented unmethylated sites as defined by the control probes, and values from 0.5 to 1.5 represent baseline levels of methylation. The middle panel provides the location of CpG dinucleotides with tick marks on the x axis. CpG density was calculated across the region using a standard density estimator and is represented by the smoothed line. The location of the CpG island was denoted on the x axis. The lower panel provides gene annotation for the genomic region. The thin outer line represents the transcript, the thin inner lines represent a coding region. Filled in boxes represent exons. On the y axis, plus and minus marks denote sense and antisense gene transcription, respectively. ( FIG. 1B ) An example of a C-DMR that was located in a CpG island shore and that overlapped a T-DMR. Liver was hypomethylated relative to brain and spleen tissues. Hypomethylation of colon tumor was observed in comparison to matched normal colon tissue and overlapped the region of liver hypomethylation. 
       FIG. 9  illustrates that genome-wide DNAm analysis showed methylation variation was more common outside of CpG islands than within them. The average M value was computed for four sets of normal brain, liver, spleen and colon. Methylation variation across tissues was determined using the standard deviation across tissues of within tissue-averaged M. For all CHARM probes located within a CGI, left plot and all CHARM probes located outside of a CGI, right plot, a smooth scatter plot was used to represent distribution of values from high to low number of points. Where tissue M variation was greater than 0.75 points were used, and where greater than 1.0, other points were used. 
     Similar CpG island shore hypo- and hypermethylation in cancer. The same comprehensive genome-wide was used approach to address cancer-specific DNA methylation. The focus was on colorectal cancer, a paradigm for cancer epigenetics because of the availability of subject-matched normal mucosa, the cell type from which the tumors arise. DNAm was analyzed on 13 colon cancers and matched normal mucosa from the same individuals, identifying 2,707 regions showing differential methylation in cancers (C-DMRs) with an FDR of 5% (Table 11 describes some of the identified C-DMR regions. The complete set of C-DMRs is available on the Nature Genetics website (nature.com/naturegenetics) see “Supplementary Data 2” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186). Plots similar to those in  FIGS. 1A-1B  for 10 of the C-DMRs are provided in  FIGS. 12A-12J ; the complete set of C-DMRs plots, ordered by statistical significance, are available online at rafalab.jhsph.edu/c-dmr-all.pdf). These C-DMRs were similarly divided between those showing hypomethylation in the cancer (compared to the normal colon) and those showing hypermethylation (1,199 (44%) and 1,508 (56%), respectively). The CHARM arrays, like other tiling arrays, do not contain repetitive sequences, so the abundance of hypomethylation was not due to enrichment for repetitive DNA, which has been shown to be hypomethylated in cancer. This similarity in amount of hypomethylation and hypermethylation was also shown in a quantile-quantile plot, in which quantiles for the observed average difference between tumor and normal sample Ms are plotted against quantiles from a null distribution constructed with the control (M=0) regions ( FIG. 3A ). 
     Although both hypomethylation and hypermethylation in cancer involved CpG island shores, there were subtle differences in the precise regions that were altered. The hypermethylation extended to include portions of the associated CpG islands in 24% of cases (termed ‘overlap’ in  FIG. 2 ), which could account for the island hypermethylation frequently reported in cancer, even though that is not the predominant site of modification. In contrast, the hypomethylation extended to between 2 and 3 kb from the associated island in 10% of cases and was not associated with an island in 35% of cases ( FIG. 2 ). 
     To confirm differential methylation in colon tumors, additional bisulfite pyrosequencing validation of nine C-DMRs, including five regions showing hypermethylation and four regions with hypomethylation, in an average of 50 primary cancer and normal mucosal samples per gene was carried out. For all of the genes, the pyrosequencing data matched the CHARM data (P values ranging from 10 −4  to 10 −17 ) ( FIGS. 3B-3J  and Table 3). Thus, CHARM was precise in identifying both T-DMRs and C-DMRs. 
     Our screening process was effective at identifying known targets of altered DNAm in cancer. For example, 10 of the 25 most statistically significant C-DMRs have previously been reported to show altered DNAm in cancer, for example, WNK2, hypermethylated in glioblastoma (Hong, et al., Proc. Natl. Acad. Sci. USA 104:10974-10979, 2007) and HOXA6, hypermethylated in lymphoid malignancies (Strathdee et al., Clin. Cancer Res. 13, 5048-5055, 2007). However, hundreds of genes not previously described were also identified by this screening. For example, for hypermethylation, we identified genes encoding GATA-2, an important regulator of hematopoetic differentiation (Cantor et al., J. Exp. Med. 205, 611-624, 2008), and RARRES2, whose expression is decreased in intestinal adenomas (Segditsas et al., Hum. Mol. Genet. 17:3864-3875, 2008). For hypomethylation, we identified genes encoding DPP6, a biomarker for melanoma (Jaeger et al., Clin. Cancer Res. 13, 806-815, 2007), MRPL36, a DNA helicase that confers susceptibility to breast cancer (Seal et al.,  Nat. Genet.  38, 1239-1241, 2006), and MEST, a known target of hypomethylation and loss of imprinting in breast cancer (Pedersen et al., Cancer Res. 59:5449-5451, 1999). Note that although previous T-DMR screens have focused on CpG islands, which we show account for only 8% of T-DMRs, our screen did identify CpG island loci validated by others as well, for example, PAX6, OSR1 and HOXC12. Thus, cancer, like normal tissues, involves changes in DNAm in CpG island shores, with comparable amounts of hypomethylation and hypermethylation but with subtle differences in the precise distribution of these alterations with respect to the associated CpG island. These differences will have important functional implications for gene expression, as discussed later. 
       FIG. 2  illustrates the distribution of distance of T-DMRs and C-DMRs from CpG islands. In the plots, bars denoted “Islands” were regions that cover or overlap more than 50% of a CpG island. Bars denoted “Overlap” were regions that overlap 0.1-50% of a CpG island. Regions denoted by (0, 500) did not overlap islands but are located ≤500 bp of islands. Regions denoted by (500, 1,000) were located &gt;500 and ≤1,000 bp from an island. Regions denoted by (1,000, 2,000) were regions &gt;1,000 bp and ≤2,000 bp from an island. Regions denoted by (2000, 3000) were located &gt;2,000 bp and ≤3,000 bp from an island. Regions denoted &gt;3,000 were &gt;3,000 bp from an island. The percentage of each class was provided for CpG regions (the CHARM arrays themselves, null hypothesis), tissue-specific differentially methylated regions (T-DMRs), cancer-specific differentially methylated regions (C-DMRs), and the latter subdivided into regions of cancer-specific hypermethylation and hypomethylation. 
       FIGS. 3A-3J  illustrate similar numbers of sites of hypomethylation and hypermethylation in colon cancer. ( FIG. 3A ) A quantile-quantile plot showed a similar number of sites of hypomethylation and hypermethylation in colon cancer. The quantiles of the differences in M values between tumor and normal colon tissues were plotted against the quantiles of a null distribution formed using the differences seen in the control regions. Points deviating from the diagonal were not expected by chance, and a similar proportion is seen for hypomethylation and hypermethylation in cancer. ( FIG. 3B-3J ) Bisulfite pyrosequencing confirms the prevalence of five hypermethylated and four hypomethylated C-DMR shores in a large set of colon tumor and normal mucosa samples. Box plots represent degree of DNA methylation as measured using bisulfate pyrosequencing. ( FIG. 3B ) DLX5 (distal-less homeobox 5). ( FIG. 3C ) LRFN5 (leucine-rich repeat and fibronectin type III domain containing 5). ( FIG. 3D ) HOXA3 (homeobox A3). ( FIG. 3E ) SLITRK1 (SLIT and NTRK like family, member 1). ( FIG. 3F ) FEZF2 (FEZ family zinc finger 2). (Figuref 3G) TMEM14A (transmembrane protein 14A). ( FIG. 3H ) ERICH1 (glutamate-rich 1). ( FIG. 3I ) FAM70B (family with sequence similarity 70, member B). ( FIG. 3J ) PMEPA1 (prostate transmembrane protein, androgen induced 1). n, number of samples analyzed by pyrosequencing. 
     Gene expression is linked to non-CpG-island methylation. Because the identification of CpG island shores was unexpected, the functional relationship between their differential methylation and the expression of associated genes was explored. To address tissue- and cancer-specific DNAm, gene expression was analyzed across the genome in five primary brains and livers from the same autopsy specimens. and in four colon cancers and subject-matched normal mucosa; all samples were from subjects for whom genome-wide methylation analysis data had been collected. Methylation of T-DMRs showed a strong inverse relationship with differential gene expression, even though these DMRs were not CpG islands but rather CpG island shores. The relationship between DNAm and gene expression was greater for DMRs in which one of the two measured points had approximately no methylation (‘none-to-some’ methylation compared to ‘some-to-more’ or ‘some-to-less’ methylation), particularly for hypomethylation ( FIG. 4 ). The significant association of gene expression with T-DMRs was true even when the DMR was 300-2,000 bp from the transcription start site, for example, average log-ratio values of 0.84 and 0.35 (P &lt;10 −37  and 10) for some-to-none and some-to-more/less methylation, respectively, comparing liver to brain expression ( FIG. 4 ). Moreover, when T-DMRs were related to changes in gene expression from over 242 samples, representing 20 different tissue types, it was found that 5,352 of the 8,910 genes that were differentially expressed across the 20 tissues were within 2 kb of a T-DMR, much more than expected by chance (P&lt;10 −15 ). For C-DMRs as well, even though there were fewer of them than T-DMRs, there was a significant association of gene expression with DNAm: P&lt;10 −6  and P&lt;10 −3  for hypermethylation and hypomethylation, respectively; again, the relation was much more marked when one of the two measured points had no methylation ( FIGS. 10A-10J ; the complete set is available on the Nature Genetics website (nature.com/naturegenetics) see “Supplementary  FIG. 2 ” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186). 
     The inverse relationship between DNAm and transcription was validated at eight CpG island shores, two T-DMRs and six C-DMRs in tissues and colon cancers, respectively, using quantitative real-time PCR. Both of the T-DMRs were in shores, one located 844 bp upstream of the promoter and one within the gene body. Similarly, all six of the C-DMRs assayed were in shores, with five located in the gene promoter and one within the gene body (Table 4). These quantitative data provided additional support for a strong relationship between differential methylation in CpG island shores and transcription of associated genes. This functional relationship between gene expression and shore methylation applies to shores located within 2 kb of an annotated transcriptional start site but leaves open the possibility of additional regulatory function for shores located in intragenic regions or gene deserts. 
       FIG. 4  shows that gene expression was strongly correlated with T-DMRs at CpG island shores. For each brain versus liver T-DMR, the closest annotated gene on the Affymetrix HGU133A microarray was found, resulting in a total of 2,041 gene-T-DMR pairs. Plotted are log (base 2) ratios of liver to brain expression against ΔM values for liver and brain DNAm. Dots represented T-DMRs located within 300 bp from the corresponding gene&#39;s transcriptional start site (TSS). Dots represented T-DMRs that were located from 300 to 2,000 bp from the TSS of an annotated gene. Dots, in the middle, represented log ratios for all genes further than 2 kb from an annotated TSS. 
       FIGS. 10A-10J  illustrate that most tissue-specific differential DNA methylation were located at CpG island shores. The top 50 T-DMRs, ordered by statistical significance. Displays are as in  FIG. 1A . The upper panels are plots of M value versus genomic location for brain, liver, and spleen. Each point represents the methylation level of an individual sample for a given probe. The curve represents averaged smoothed M values, described in detail in the Methods. Due to the scale and standardization used, M values which range from −0.5 to 0.5 represented unmethylated sites as defined by the control probes, and values from 0.5 to 1.5 represented baseline levels of methylation. The middle panels provide the location of CpG dinucleotides with tick marks on the x-axis. CpG density was calculated across the region using a standard density estimator and is represented by the smoothed line. The location of the CpG island was denoted on the x-axis. The lower panels provide gene annotation for the genomic region. The thin outer line represents the transcript, the thin inner lines represent a coding region. Filled in boxes represent exons. On the y-axis, plus and minus marks denote sense and antisense gene transcription respectively. 
     Shore-linked silencing reversed by methyltransferase inhibition. The previous data, although compelling, are associative in nature. For a more functional analysis, DNA methylation and gene expression data from tissues studied in the current work were compared to a rigorous analysis using hundreds of expression microarray experiments published earlier (Gius et al., Cancer Cell 6:361-371, 2004), which tested the effects on gene expression of 5-aza-2′-deoxycytidine (AZA), and also to double DNA methyltransferase 1 and 3B somatic cell knockout (DKO) experiments. Genes from the present study that had DMRs meeting an FDR &lt;0.05 and that showed differential expression in the tissues at P&lt;0.05 were compared to genes that had significant P values after AZA or DKO. Of 27 DMRs that showed relative hypermethylation with gene silencing in tissues, 23 were activated by AZA ( FIG. 5A  and Tables 12 and 13). Similarly, of 25 DMRs that showed relative hypermethylation with gene silencing in tissues, all 25 were activated by DKO ( FIG. 5B  and Tables 12 and 13). Thus, both chemical and genetic demethylation cause changes in gene expression similar to those associated with increased methylation of CpG island shores. 
       FIGS. 5A-5B  show that genes downregulated in association with T-DMR shore hypermethylation were activated by 5-aza-2′-deoxycytidine treatment of colon cancer cell line HCT116 and knockout of DNA methyltrasferase 1 and 3b in HCT116. ( FIG. 5A ) Genes significantly upregulated (P&lt;0.05) after treatment of HCT116 cells with 5-aza-2′-deoxycytidine (AZA) that were also associated with a relatively hypermethylated T-DMR showing a significant change in gene expression (P&lt;0.05): 23/27 genes are activated by AZA. ( FIG. 5B ) Genes significantly upregulated (P&lt;0.05) after knockout of DNA methyltransferases 1 and 3b (DKO) in HCT116 cells that were also associated with a relatively hypermethylated T-DMRs showing a significant change in gene expression (P&lt;0.05): 25/25 genes were activated by DKO. Plotted are log (base 2) ratios of expression of AZA/untreated, DKO/HCT116 and relatively hypermethylated/hypomethylated tissue. 
     DMRs are associated with alternative transcription. The question as to what the function of differential methylation at CpG island shores might be was next addressed. One possibility was alternative transcription. Both the T-DMRs and C-DMRs often involved alternative transcripts, as defined by cap analysis gene expression (CAGE): 68% and 70% of the T-DMRs and C-DMRs, respectively, were not within 500 bp of an annotated transcriptional start site but were within 500 bp of an alternative transcriptional start site. By chance, only 58% were expect to have this relationship (P&lt;10 −15 ). These results suggested that DNA methylation might regulate alternative transcription in normal differentiation and cancer. Rapid amplification of cDNA ends (RACE) experiments were therefore carried out in order to confirm the presence of alternative transcripts and their differential expression in cancer. Three colon tumor and subject-matched normal mucosa were examined at the PIP5K1A locus, a C-DMR that is hypomethylated in colon tumors, and confirmed that an alternative RNA transcript is produced in colon tumors compared to their matched normal counterparts (B online). Thus, a key function for differential methylation during differentiation may be alternative transcription, and the role of altered DNAm in cancer may in part be disruption of the regulatory control of specific promoter usage. 
       FIGS. 11A-11C  illustrate that bisulfite pyrosequencing confirmed the prevalence of 4 hypomethylated C-DMR shores in a large set of colon tumor and normal mucosa samples. Box-plots represent DNA methylation level measured using bisulfite pyrosequencing. a, transmembrane protein 14A (TMEM14A); b, glutamate-rich 1 (ERICH1); c, family with sequence similarity 70, member B (FAM70C); d, prostate transmembrane protein, androgen induced 1 (TMEPAI), (n) equals the number of samples analyzed by pyrosequencing. 
     Mouse DNAm discriminates human tissues, even far from genes. A compelling argument for the functional importance of differential DNAm of CpG island shores would be their conservation across species. One might expect DMRs near transcriptional start sites to be conserved because the genes are conserved. However, when the relationship between gene-distant T-DMRs (2-10 kb away from an annotated gene) and sequence conservation using the phastCons28way table from the University of California Santa Cruz genome browser was examined, it was found that 48% of differentially methylated regions showed sequence conservation. Furthermore, 91% of DMRs were located within 1 kb of a highly conserved region (P&lt;0.001). 
     To address whether the DNA methylation itself is conserved across species, a mouse CHARM array was created with ˜2.1 million features independently of the human array. Tissue replicates were then isolated from each of three mice, corresponding to the tissues examined in the human T-DMR experiments, and then mapped these methylation data across species using the UCSC LiftOver tool. The interspecies correspondence of tissue-specific methylation was notable, and unsupervised clustering perfectly discriminated among the tissues, regardless of the species of origin ( FIG. 6 ; P&lt;10 −9 ). Perfect discrimination among the tissues was found even when the analysis was limited to gene-distant DMRs ( FIGS. 12A-12J ; the complete set is available on the Nature Genetics website (nature.com/naturegenetics) see “Supplementary  FIG. 4 ” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186)). Thus, DNAm itself is highly conserved across 50 Myr of evolution (approximately 51% of mapped DNAm sites were conserved). It was also noticed relatively little heterogeneity in tissue-specific methylation in the mouse compared to the human (height of the cluster bars in  FIG. 6 ), suggesting a genetic-epigenetic relationship, as the mice are inbred. 
       FIG. 6  shows clustering of human tissue samples using mouse T-DMRs resulted in perfect discrimination of tissues. The M values of all tissues from the 1,963 regions corresponding to mouse T-DMRs that mapped to the human genome were used for unsupervised hierarchical clustering. By definition, the mouse tissues were segregated. Notably, all of the human tissues were also completely discriminated by the regions that differ in mouse tissues. The three major branches in the dendrograms corresponded perfectly to tissue type regardless of species. Columns represent individual samples, and rows represent regions corresponding to mouse T-DMRs. The heat map shows M values, with some being more methylated and some being less methylated. 
       FIGS. 12A-12J  illustrate that most cancer-specific differential DNA methylation was located at CpG island shores. The top 50 C-DMRs, ordered by statistical significance. Displays are as in  FIG. 1B . The upper panels are plots of M value versus genomic location for brain, liver, spleen, normal colon, and colon cancer. Each point (shown only for normal colon and colon cancer) represented the methylation level of an individual sample for a given probe. The curve represents averaged smoothed M values, described in detail in the Methods. Due to the scale and standardization used, M values which range from −0.5 to 0.5 represent unmethylated sites as defined by the control probes, and values from 0.5 to 1.5 represent baseline levels of methylation. The middle panels provide the location of CpG dinucleotides with tick marks on the x-axis. CpG density was calculated across the region using a standard density estimator and is represented by the smoothed line. The location of the CpG island is denoted on the x-axis. The lower panels provide gene annotation for the genomic region. The thin outer line represents the transcript, the thin inner lines represent a coding region. Filled in boxes represent exons. On the y-axis, plus and minus marks denote sense and antisense gene transcription respectively. 
     The location of C-DMRs overlaps that of T-DMRs. Because both C-DMRs and T-DMRs were located at CpG island shores, we then asked whether they occurred in similar locations. DMRs in which the methylation difference was from no methylation to some methylation, that is, those DMRs for which the gene expression data above showed a strong relationship between ‘none-to-some’ methylation and gene silencing were focused on. Notably, it was found that 52% of the C-DMRs overlapped a T-DMR, compared to only 22% expected by chance (P&lt;10 −14 ), when using an FDR of 5% for defining T-DMRs. Although these data are significant, the definition of a T-DMR based on FDR of 5% is conservative. It was therefore also asked directly whether C-DMRs are enriched for tissue variation in DNAm by computing an averaged F-statistic (comparison of cross-tissue to within-tissue variation) at each C-DMR. The cross-tissue variation in normal tissues was significant at 64% of the C-DMRs, compared to 20% of randomly selected CpG regions on the array matched for size (P&lt;10 −143 ). When DMRs were defined using an FDR of 5%, 1,229 of 2,707 C-DMRs overlapped a T-DMR, of which 265, 448 and 185 are brain-, liver- and spleen-specific, respectively, and 331 show variation among all of the tissues (Table 14; the complete data set is available on the Nature Genetics website (nature.com/naturegenetics) see “Supplementary Data 4” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186). The colon C-DMRs were highly enriched for overlap with liver T-DMRs (P &lt;10 −15 ), and liver was embryologically closest to colon of the autopsy tissues studied. For example, the C-DMR located in the CpG island shore upstream of the HS3ST4 (heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4) gene is hypomethylated in colon cancer compared to normal colon and coincides with a T-DMR that distinguishes liver from other tissues ( FIG. 1B ). The correspondence between C-DMRs and T-DMRs was so marked that when unsupervised clustering of the normal brain, liver and spleen, using the M values from the C-DMRs was carried out, there was perfect discrimination of the tissues ( FIGS. 7A-7B ). 
     Most tissue-specific methylation difference more commonly involves hypomethylation, although this varies by tissue type with 50% of liver, 62% of spleen, and 79% of brain DMRs representing hypomethylation, and cancer-specific methylation differences slightly more frequently involve hypermethylation (56%:44%). For both T-DMRs and C-DMRs, when there was differential methylation, it was common that at least one of the tissues was completely unmethylated (68% and 37%, respectively). Furthermore, hypomethylated C-DMRs were twice as likely to resemble another tissue type, such as liver, than were hypermethylated C-DMRs (82% versus 61%, P&lt;10 −31 ), even though hypermethylated C-DMRs overlapped T-DMRs 1.5-fold more frequently than did hypomethylated C-DMRs (54% versus 35%, P&lt;10 −21 ). 
     To further explore the relationship between differentiation and type of methylation change, Gene Ontology (GO) analysis was carried out for both hypomethylated and hypermethylated C-DMRs in the cancers (see Methods). The GO analysis showed enrichment for development and pluripotency-associated genes for both hyper- and hypomethylated C-DMRs (P&lt;0.01) (Table 5). Hypomethylated C-DMRs were also enriched for genes associated with differentiated cellular functions for lineages other than the colon (P&lt;0.01) (Table 5). Thus, cancer-specific DNA methylation predominantly involves the same sites that show normal DNAm variation among tissues, particularly at genes associated with development. 
     Next, the magnitude of differential methylation and variation in C-DMRs and T-DMRs were examined. The ΔM values for tissue and cancer DMRs differed markedly from nonmethylated controls or randomly selected regions (the latter have an average value comparable to controls but with significant tails, as by definition they may contain DMRs themselves) ( FIGS. 8A-8D ). The ΔM values for normal tissues were comparable across the tissues, but the ΔM values between normal and cancer tissues were on average approximately half the ΔM between normal tissue pairs ( FIG. 8E ), which is logical given that the cancers are compared with their tissue of origin. Another difference between cancer and normal tissues was an increase in the inter-individual variation in M among the colon cancers, which was on average ˜50% greater than the inter-individual variation among the normal colons ( FIG. 8F ), a result which may help to explain tumor cell heterogeneity. Given the strong inter-individual variability found in cancer, 205/2,707 C-DMRs were identified that were consistently differentially methylated between the colon tumor and matched normal mucosa from all 13 individuals examined (Table 18; the complete data set is available on the Nature Genetics website (nature.com/naturegenetics) see “Supplementary Data 4” in the Supplementary Information for Irizarry et al., Nature Genetics 41(2):178-186). These regions, heavily over-represented for development and morphogenesis genes, provide a smaller, more focused set of regions for biomarker discovery and carcinogenesis studies. 
       FIGS. 7A-7B  show clustering of normal tissue samples using C-DMRs resulted in perfect discrimination of tissues. The M values of all tissues from the 2,707 regions corresponding to C-DMRs were used for unsupervised hierarchical clustering. ( FIG. 7A ) By definition, the colon tumors and matched normal mucosa were segregated. The two major branches in the dendrograms corresponded perfectly to tissue type. ( FIG. 7B ) Notably, all of the normal brains, spleens and livers were also completely discriminated by the regions that differ in colon cancer. The three major branches in the dendrograms corresponded perfectly to tissue type. Columns represent individual samples, and rows represent regions corresponding to C-DMRs. The heat map shows M values, with some being more methylated and some being less methylated. 
       FIGS. 8A-8F  show the magnitude of differential methylation and variation in C-DMRs and T-DMRs. ( FIGS. 8A-8D ) Box plots of average ΔM values over all DMRs, compared to randomly chosen regions and unmethylated control regions, matched for length. ( FIG. 8A ) Liver versus brain. ( FIG. 8B ) Spleen versus brain. ( FIG. 8C ) Spleen versus liver. ( FIG. 8D ) Colon cancer versus normal colonic mucosa. ( FIG. 8E ) Differences in DNA methylation were greater in magnitude among normal tissues than were differences between colon tumors and matched normal mucosa. For all DMRs the average ΔM was computed. These values were then stratified into T-DMRs, hypermethylated C-DMRs and hypomethylated C-DMRs. T-DMRs were further stratified according to brain versus liver, brain versus spleen and liver versus spleen pairwise comparisons. The box plots represented absolute values of the AMs. ( FIG. 8F ) Inter-individual variation in M was larger among colon tumors than matched normal mucosa. For each C-DMR the average interindividual s.d. of the M values was computed. The box plots represent these values for normal colon mucosa and colon tumors. 
       FIG. 15  illustrates that gene expression was strongly correlated with C-DMRs at CpG island shores. For each colon tumor versus normal mucosa C-DMR the closest annotated gene on the Affymetrix HGU133A microarray was found, resulting in a total of 650 gene/C-DMR pairs. Plotted are log (base 2) ratios of colon tumor to normal expression against delta M values for colon tumor and normal DNAm. Dots represent C-DMRs located within 300 bp from the corresponding gene&#39;s transcriptional start site (TSS). Dots represent C-DMRs that are located from 300-2000 bp from the TSS of an annotated gene. Dots, in the middle, represent log ratios for all genes further than 2 kb from an annotated TSS. 
       FIG. 16  illustrates that differences in DNA methylation were greater in magnitude among normal tissues than were differences between colon tumors and matched normal mucosa. For all DMRs the average delta M was computed. These values were then stratified into T-DMRs, hypermethylated C-DMRs and hypomethylated C-DMRs. T-DMRs were further stratified according to brain versus liver, brain versus spleen, and liver versus spleen pair-wise comparisons. The box-plots represent absolute values of the delta Ms. 
       FIG. 17  shows that inter-individual variation in M was larger among colon tumors than matched normal mucosa. For each C-DMR the average inter-individual standard deviation of the M-values were computed. The box-plots represent these values for normal colon mucosa and colon tumors. 
       FIGS. 18A-18B  demonstrate alternate gene transcription origin in colon tumors at a CpG island shore.  FIG. 18A , a schematic overview of the PIP5K1A gene locus. C-DMR represents the genomic region that is hypomethylated in colon tumors as compared to normals.  FIG. 18B , the arrow indicates a 220 bp fragment present in 3 colon tumors but not normal mucosa from the same individual amplified by the Sp3 primer and the 5′ RACE anchor primer. 
       FIG. 19  shows an example of non-conventional CpG island, a C-DMR that was not adjacent to a conventionally defined CpG island. Upper panel: plot of M value versus genomic location for brain, liver, spleen, normal colon, colon tumor. Each point represented the methylation level of an individual sample for each probe across the region. The smoothed line represents averaged, smoothed M values for each tissue, described in detail in the methods. M values which range from −0.5 to 0.5 represent unmethylated points and values from 0.5 to 1.5 represent baseline levels of methylation due to the scale and standardization used. The middle panel provides the location of CpG dinucleotides with black tick marks on the x-axis. CpG density was calculated across this region using a standard density estimator and is represented by the smoothed black line. The location of non-conventional CpG islands, defined using Hidden Markov modeling, is denoted on the x-axis as an orange line. The lower panel provides gene annotation for the genomic region. The thin outer grey line represents the start of transcription, the thin inner lines represent the start and end of a coding region. Filled in grey boxes represent exons. On the y-axis, plus and minus marks denote sense and antisense gene transcription respectively. 
       FIG. 20  illustrates the methylation of mouse T-DMRs completely discriminated tissues regardless of species of origin, even for T-DMRs &gt;2 kb from an annotated gene. The M values of all tissues from the 957 regions corresponding to mouse T-DMRs that mapped to the human genome and were greater than 2 kb from an annotated gene were used for unsupervised hierarchical clustering. By definition, the mouse tissues were segregated. Surprisingly, all of the human tissues were also completely discriminated by the regions that differ in mouse tissues. The three major branches in the dendrograms correspond perfectly to tissue type regardless of species. Columns represent individual samples, and rows represent regions corresponding to mouse T-DMRs. The heatmap displays M values, with some being more methylated and some being less methylated. 
     Although the invention has been described with reference to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Bisulfite pyrosequencing confirms differential DNA methylation at CpG island shores but not the associated island. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 Location a   
                 Region 
                 Tissue b   
                 CG1 
                 CG2 
                 CG3 
                 CG4 
                 CG5 
                 CG6 
                 CG7 
                 CG8 
                 CG9 
               
               
                   
               
               
                 PCDH9 
                 +3,338 
                 Shore 
                 Brain 
                 32 
                 26 
                 12 
                 39 
                 19 
                 22 
               
               
                   
                   
                   
                 Spleen 
                 91 
                 71 
                 31 
                 76 
                 66 
                 60 
               
               
                   
                   
                   
                 P value 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 0.003 
               
               
                   
                 −267 
                 Island 
                 Brain 
                 2 
                 3 
                 4 
                 2 
                 3 
                 5 
                 2 
                 3 
                 2 
               
               
                   
                   
                   
                 Spleen 
                 2 
                 3 
                 3 
                 2 
                 3 
                 6 
                 2 
                 4 
                 3 
               
               
                   
                   
                   
                 P value 
                 0.032 
                 0.298 
                 0.336 
                 0.108 
                 0.475 
                 0.150 
                 0.393 
                 0.141 
                 0.011 
               
               
                 HEY1 
                 +3,381 
                 Shore 
                 Brain 
                 54 
                 53 
                 51 
                 51 
               
               
                   
                   
                   
                 Liver 
                 70 
                 84 
                 87 
                 71 
               
               
                   
                   
                   
                 P value 
                 .023 
                 &lt;.001 
                 &lt;.001 
                 &lt;.007 
               
               
                   
                 +2,207 
                 Island 
                 Brain 
                 4 
                 7 
                 3 
                 4 
                 4 
                 5 
                 1 
                 8 
                 5 
               
               
                   
                   
                   
                 Liver 
                 3 
                 6 
                 3 
                 4 
                 4 
                 6 
                 2 
                 9 
                 23 
               
               
                   
                   
                   
                 P value 
                 0.349 
                 0.309 
                 0.226 
                 0.460 
                 0.630 
                 0.252 
                 0.017 
                 0.336 
                 0.255 
               
               
                 HAGH 
                 +2,192 
                 Shore 
                 Liver 
                 26 
                 30 
                 22 
                 18 
                 7 
                 6 
                 23 
                 33 
               
               
                   
                   
                   
                 Spleen 
                 93 
                 93 
                 82 
                 56 
                 20 
                 20 
                 86 
                 95 
               
               
                   
                   
                   
                 P value 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 0.017 
                 0.017 
               
               
                   
                 +206 
                 Island 
                 Liver 
                 2.1 
                 1.1 
                 2.1 
                 3.4 
                 2.3 
                 6.7 
                 2.7 
                 2.2 
                 3 
               
               
                   
                   
                   
                 Spleen 
                 2.2 
                 1.6 
                 2.9 
                 3.7 
                 2.2 
                 2.2 
                 2.1 
                 2.1 
                 3.6 
               
               
                   
                   
                   
                 P value 
                 0.608 
                 0.207 
                 0.433 
                 0.803 
                 0.058 
                 0.342 
                 0.262 
                 0.529 
                 0.504 
               
               
                 SLMO2 
                 +1,125 
                 Shore 
                 Normal 
                 89 
                 63 
                 85 
                 46 
                 68 
                 30 
                 78 
                 81 
                 75 
               
               
                   
                   
                   
                 Tumor 
                 37 
                 28 
                 34 
                 19 
                 30 
                 13 
                 34 
                 40 
                 35 
               
               
                   
                   
                   
                 P value 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 0.005 
                 0.002 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 0.002 
               
               
                   
                 +40 
                 Island 
                 Normal 
                 4 
                 2 
                 3 
                 3 
                 6 
                 4 
                 3 
                 2 
                 3 
               
               
                   
                   
                   
                 Tumor 
                 4 
                 1 
                 3 
                 3 
                 3 
                 4 
                 3 
                 2 
                 2 
               
               
                   
                   
                   
                 P value 
                 0.619 
                 0.233 
                 0.293 
                 0.546 
                 0.302 
                 0.364 
                 0.461 
                 0.204 
                 0.586 
               
               
                   
               
               
                 Gene 
                 Location a   
                 Region 
                 Tissue b   
                 CG10 
                 CG11 
                 CG12 
                 CG13 
                 CG14 
                 CG15 
                 CG16 
                 CG17 
                 CG18 
               
               
                   
               
               
                 PCDH9 
                 +3,338 
                 Shore 
                 Brain 
               
               
                   
                   
                   
                 Spleen 
               
               
                   
                   
                   
                 P value 
               
               
                   
                 −267 
                 Island 
                 Brain 
                 3 
                 3 
                 3 
                 5 
                 5 
                 4 
                 3 
                 3 
                 4 
               
               
                   
                   
                   
                 Spleen 
                 3 
                 3 
                 3 
                 3 
                 5 
                 4 
                 3 
                 4 
                 3 
               
               
                   
                   
                   
                 P value 
                 0.661 
                 0.265 
                 0.208 
                 0.420 
                 0.051 
                 0.133 
                 0.885 
                 0.783 
                 0.270 
               
               
                 HEY1 
                 +3,381 
                 Shore 
                 Brain 
               
               
                   
                   
                   
                 Liver 
               
               
                   
                   
                   
                 P value 
               
               
                   
                 +2,207 
                 Island 
                 Brain 
                 5 
                 7 
                 7 
                 4 
               
               
                   
                   
                   
                 Liver 
                 26 
                 26 
                 8 
                 8 
               
               
                   
                   
                   
                 P value 
                 0.179 
                 0.238 
                 0.432 
                 0.001 
               
               
                 HAGH 
                 +2,192 
                 Shore 
                 Liver 
               
               
                   
                   
                   
                 Spleen 
               
               
                   
                   
                   
                 P value 
               
               
                   
                 +206 
                 Island 
                 Liver 
                 1.1 
                 2.2 
                 1.8 
                 1.2 
                 1.4 
                 0.6 
                 1.7 
                 0.6 
                 4.2 
               
               
                   
                   
                   
                 Spleen 
                 1.2 
                 4.4 
                 1.9 
                 1.8 
                 2.5 
                 2.1 
                 4.4 
                 0.8 
                 7.8 
               
               
                   
                   
                   
                 P value 
                 0.782 
                 0.060 
                 0.832 
                 0.366 
                 0.074 
                 0.307 
                 0.073 
                 0.141 
                 0.015 
               
               
                 SLMO2 
                 +1,125 
                 Shore 
                 Normal 
                 82 
                 40 
                 85 
                 81 
                 43 
                 65 
                 76 
                 76 
                 87 
               
               
                   
                   
                   
                 Tumor 
                 36 
                 18 
                 38 
                 36 
                 19 
                 30 
                 39 
                 37 
                 46 
               
               
                   
                   
                   
                 P value 
                 &lt;.001 
                 0.036 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 &lt;.001 
                 0.003 
                 &lt;.001 
               
               
                   
                 +40 
                 Island 
                 Normal 
                 2 
                 3 
                 3 
                 4 
                 2 
                 7 
                 5 
               
               
                   
                   
                   
                 Tumor 
                 4 
                 3 
                 2 
                 4 
                 2 
                 7 
                 6 
               
               
                   
                   
                   
                 P value 
                 0.263 
                 0.173 
                 0.369 
                 0.253 
                 0.928 
                 0.230 
                 0.509 
               
               
                   
               
               
                   a Location represents distance in base pairs, +denoting upstream and −downstream, from the transcriptional start site to the closest CpG site measured by bisulfite pyrosequencing (CG1). CG1-18 denote individual CpG site measured by bisulfite pyrosequencing. Values are percent methylation. The coordinates for each CpG site measured by pyrosequencing are provided in Supplementary Table 7. 
               
               
                   b Brain, spleen, and liver tissues are from the same individuals. Normal and tumor represent matched colon tumor and mucosa from the same individuals. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Bisulfite pyrosequencing confirms differential DNA 
               
               
                 methylation at 4 additional CpG island shores 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 Location a   
                 Region 
                 Tissue b   
                 CG1 
                 CG2 
                 CG3 
                 CG4 
                 CG5 
                 CG6 
               
               
                   
               
               
                 SEMA3C 
                 −409 
                 Shore 
                 Tumor 
                 31 
                 32 
                 32 
                 34 
                 31 
                 26 
               
               
                   
                   
                   
                 Normal 
                 65 
                 71 
                 68 
                 64 
                 63 
                 52 
               
               
                   
                   
                   
                 P value 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
               
               
                 DSCAML1 
                 +2,875 
                 Shore 
                 Brain 
                 34 
                 30 
                 29 
                 28 
                 33 
                 26 
               
               
                   
                   
                   
                 Liver 
                 86 
                 79 
                 87 
                 89 
                 76 
                 71 
               
               
                   
                   
                   
                 P value 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 0.004 
               
               
                 GPT2 
                 −2,984 
                 Shore 
                 Spleen 
                 93 
                 93 
                 82 
                 56 
                 20 
                 20 
               
               
                   
                   
                   
                 Liver 
                 26 
                 30 
                 22 
                 18 
                 7 
                 5 
               
               
                   
                   
                   
                 Pvalue 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
               
               
                 ZNF532 
                 +1,127 
                 Shore 
                 Liver 
                 97 
                 96 
                 92 
                 93 
                 79 
                 96 
               
               
                   
                   
                   
                 Brain 
                 34 
                 38 
                 26 
                 30 
                 23 
                 24 
               
               
                   
                   
                   
                 Pvalue 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
               
               
                   
               
               
                 Gene 
                 Location a   
                 Region 
                 Tissue b   
                 CG7 
                 CG8 
                 CG9 
                 CG10 
                 CG11 
                 CG12 
               
               
                   
               
               
                 SEMA3C 
                 −409 
                 Shore 
                 Tumor 
                 24 
                 21 
                 23 
                 9 
                 9 
                 1 
               
               
                   
                   
                   
                 Normal 
                 58 
                 41 
                 43 
                 21 
                 17 
                 2 
               
               
                   
                   
                   
                 P value 
                 0.007 
                 &lt;0.001 
                 0.001 
                 0.003 
                 &lt;0.001 
                 0.048 
               
               
                 DSCAML1 
                 +2,875 
                 Shore 
                 Brain 
                 33 
                 26 
                 38 
                 23 
                 26 
               
               
                   
                   
                   
                 Liver 
                 88 
                 82 
                 98 
                 70 
                 77 
               
               
                   
                   
                   
                 P value 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
                 &lt;0.001 
               
               
                 GPT2 
                 −2,984 
                 Shore 
                 Spleen 
                 86 
                 95 
               
               
                   
                   
                   
                 Liver 
                 23 
                 33 
               
               
                   
                   
                   
                 Pvalue 
                 &lt;0.001 
                 &lt;0.001 
               
               
                 ZNF532 
                 +1,127 
                 Shore 
                 Liver 
                 98 
                 89 
               
               
                   
                   
                   
                 Brain 
                 22 
                 21 
               
               
                   
                   
                   
                 Pvalue 
                 &lt;0.001 
                 &lt;0.001 
               
               
                   
               
               
                   a Location is distance in base pairs, +denoting upstream and −downstream, from the transcriptional start site to closest CpG site measured by bisulfite pyrosequencing (CG1). CG1-12 denote individual CpG sites measured by bisulfite pyrosequencing. Values are percent methylation. The coordinates for each site are provided in Supplementary Table 7. 
               
               
                   b Brain, spleen, and liver tissues are from the same individuals. Normal and tumor represent matched colon tumor and mucosa from the same individuals. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Bisulfite pyrosequencing confirms differential DNA methylation 
               
               
                 at 9 C-DMRs in colon tumor and normal colon mucosa samples. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 CHARM 
                 Normal 
                 Tumor 
                   
                   
                   
                   
               
               
                 C-DMR 
                 Gene 
                 methylation a   
                 mean b   
                 mean b   
                 CN c   
                 CT c   
                 Matched d   
                 P 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Chr7: 
                 DLX5 
                 T &gt; N 
                 8 
                 22 
                 53 
                 61 
                 42 
                 &lt;10 −6    
               
               
                 96491680-96494485 
               
               
                 Chr14: 
                 LRFN5 
                 T &gt; N 
                 23 
                 44 
                 61 
                 65 
                 55 
                 &lt;10 −14   
               
               
                 41147653-41148722 
               
               
                 Chr7: 
                 HOXA3 
                 T &gt; N 
                 52 
                 72 
                 52 
                 59 
                 44 
                 &lt;10 −16   
               
               
                 27129188-27131713 
               
               
                 Chr13: 
                 SLITRK1 
                 T &gt; N 
                 36 
                 46 
                 56 
                 51 
                 26 
                      0.0009 
               
               
                 83352750-83353823 
               
               
                 Chr3: 
                 FEZF2 
                 T &gt; N 
                 16 
                 40 
                 42 
                 48 
                 39 
                 &lt;10 −14   
               
               
                 62335415-62336514 
               
               
                 Chr6: 
                 TMEM14A 
                 N &gt; T 
                 67 
                 45 
                 57 
                 64 
                 53 
                 &lt;10 −11   
               
               
                 52637426-52638797 
               
               
                 Chr8: 
                 ERICH1 
                 N &gt; T 
                 71 
                 56 
                 30 
                 34 
                 23 
                 &lt;10 −3    
               
               
                 846979-849372 
               
               
                 Chr13: 
                 FAM70B 
                 N &gt; T 
                 67 
                 50 
                 38 
                 36 
                 29 
                 &lt;10 −3    
               
               
                 113615559-113616275 
               
               
                 Chr20: 
                 TMEPAI 
                 N &gt; T 
                 29 
                 17 
                 48 
                 41 
                 30 
                 &lt;10 −6    
               
               
                 55705356-55707713 
               
               
                   
               
               
                 CN = normal colon tissue; 
               
               
                 CT = colon tumor 
               
               
                   a Methylation level reported by CHARM from greatest to least. 
               
               
                   b Mean methylation level reported by bisulfite pyrosequencing. 
               
               
                   c Total number of colon samples included in the bisulfite pyrosequencing mean methylation level reported. 
               
               
                   d Total number of colon tumor and normal samples from the same individual reported in the bisulfite pyrosequencing mean methylation level. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Relationship between DNA methylation and gene expression for 2 T-DMRs and 6 C-DMRs 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 Fold 
                   
                   
               
               
                 Gene 
                 Methylation a   
                 Region 
                 Type 
                 Distance b   
                 Distance c   
                 change d   
                 P 
                 Expression e   
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 FZD3 
                 Brain &lt; Liver 
                 Upstream Shore 
                 T-DMR 
                 844 bp 
                 7 bp 
                 28.2 
                 0.002 
                 Brain &gt; Liver 
               
               
                   
                 Brain &lt; Spleen 
                   
                   
                 844 bp 
                 7 bp 
                 34.0 
                 &lt;0.001 
                 Brain &gt; Spleen 
               
               
                 RBM38 
                 Brain &gt; Spleen 
                 Intragenic Shore 
                 T-DMR 
                 1937 bp  
                 69 bp  
                 7.0 
                 0.005 
                 Brain &lt; Spleen 
               
               
                   
                 Liver &gt; Spleen 
                   
                   
                 1937 bp  
                 69 bp  
                 4.0 
                 0.136 
                 Liver &lt; Spleen 
               
               
                 NDN 
                 Tumor &gt; Normal 
                 Promoter Shore 
                 C-DMR 
                  47 bp 
                 0 bp 
                 4.2 
                 0.025 
                 Normal &gt; Tumor 
               
               
                 TRAF1 
                 Tumor &gt; Normal 
                 Intragenic Shore 
                 C-DMR 
                 724 bp 
                 0 bp 
                 2.8 
                 0.025 
                 Normal &gt; Tumor 
               
               
                 ZNF804A 
                 Tumor &gt; Normal 
                 Promoter Shore 
                 C-DMR 
                 105 bp 
                 185 bp  
                 2.5 
                 0.047 
                 Normal &gt; Tumor 
               
               
                 CHRM2 
                 Tumor &gt; Normal 
                 Promoter Shore 
                 C-DMR 
                 433 bp 
                 0 bp 
                 2.0 
                 0.346 
                 Normal &gt; Tumor 
               
               
                 NQO1 
                 Normal &gt; Tumor 
                 Promoter Shore 
                 C-DMR 
                 146 bp 
                 216 bp  
                 2.8 
                 0.004 
                 Tumor &gt; Normal 
               
               
                 SEMA3C 
                 Normal &gt; Tumor 
                 Promoter Shore 
                 C-DMR 
                 143 bp 
                 0 bp 
                 4.8 
                 0.025 
                 Tumor &gt; Normal 
               
               
                   
               
               
                   a Methylation level reported by CHARM from greatest to least. 
               
               
                   b Base pairs to canonical transcriptional start site from the DMR. 
               
               
                   c Base pairs to an alternative transcriptional start site from the DMR. 
               
               
                   d Fold change = 2 −ΔΔCT ; ΔΔC T  is equal to (C T tissue A target gene −  C T beta actin ) − (C T tissue B target gene −  C T beta actin ). 
               
               
                   e Tissue expression from greatest to least. 
               
               
                 P was computed using a paired, two-tailed, t-test. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Distribution of C-DMRs and T-DMRs. 
               
            
           
           
               
               
               
            
               
                   
                 Total 
                   
               
               
                   
                 number 
                 Percent 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                 Cancer DMRs 
                   
                 2,707 
                 100%  
               
               
                 Colon DMRs 
                 Tumor hypermethylated 
                 1,508 
                 56% 
               
               
                   
                 Tumor hypomethylated 
                 1,199 
                 44% 
               
               
                 Tissue DMRs 
                   
                 16,379 
                 100%  
               
               
                 Brain DMRs 
                   
                 8200 
               
               
                   
                 Brain hypermethylated 
                 1717 
                 21% 
               
               
                   
                 Brain hypomethylated 
                 6483 
                 79% 
               
               
                 Liver DMRs 
                   
                 3511 
               
               
                   
                 Liver hypermethylated 
                 1763 
                 50% 
               
               
                   
                 Liver hypomethylated 
                 1748 
                 50% 
               
               
                 Spleen DMRs 
                   
                 3186 
               
               
                   
                 Spleen hypermethylated 
                 1208 
                 38% 
               
               
                   
                 Spleen hypomethylated 
                 1978 
                 62% 
               
               
                 Brain:Liver:Spleen DMRs 
                   
                 1482 
               
               
                   
               
               
                 Brain:Liver:Spleen DMRs are regions that vary in methylation across all three tissue. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Anchorage-independent growth of C-DMR associated genes assayed by soft agar analysis. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                 Expression 
                 Colonies 
                   
                 Colonies 
                   
               
               
                 Gene 
                 Methylation status a   
                 Expression b   
                 fold change c   
                 HeLa 
                 HeLa P d   
                 HCT116 
                 HCT116 P d   
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 NQO1 
                 Hypomethylated 
                 T &gt; N 
                 2.8 
                 32 
                 0.01 
                 102 
                 0.069 
               
               
                 ZNF804A 
                 Hypermethylated 
                 N &gt; T 
                 −2.5 
                 19 
                 0.27 
                 79 
                 0.005 
               
               
                 CHRM2 
                 Hypermethylated 
                 N &gt; T 
                 −2.0 
                 9 
                 &lt;0.01 
                 81 
                 0.037 
               
               
                 Vector 
                 N/A 
                 N/A 
                 N/A 
                 21 
                 N/A 
                 125 
                 N/A 
               
               
                   
               
               
                   a Methylation level of colon tumor as compared to matched normal mucosa, reported by CHARM. Hypomethylated: some methylation in normal, none in tumor. Hypermethylated: some methylation in tumor, none in normal. 
               
               
                   b Tissue expression from greatest to least. 
               
               
                   c Fold change = 2 −ΔΔCT ; ΔΔC T  is equal to (C T tissue A target gene −  C T beta actin ) − (C T tissue B target gene −  C T beta actin ). 
               
               
                   d Table shows the number of colonies, n = 4. P was computed using a paired, two-tailed, t-test. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 Location of CpG sites validated by bisulfite pyrosequencing 
               
               
                   
               
             
            
               
                 Chromosomal coordinates for CG1-CG9 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 Region 
                 Chr 
                 CG1 
                 CG2 
                 CG3 
                 CG4 
                 CG5 
               
               
                   
               
               
                 SLMO2 
                 Shore 
                 20 
                 57049852 
                 57049859 
                 57049884 
                 57049912 
                 57049933 
               
               
                 SLMO2 
                 Island 
                 20 
                 57051256 
                 57051274 
                 57051277 
                 57051280 
                 57051287 
               
               
                 PCDH9 
                 Shore 
                 13 
                 66698906 
                 66698964 
                 66699018 
                 66699044 
                 66699123 
               
               
                 PCDH9 
                 Island 
                 13 
                 66702731 
                 66702734 
                 66702745 
                 66702747 
                 66702753 
               
               
                 HEY1 
                 Shore 
                 8 
                 80839112 
                 80839160 
                 80839206 
                 80839272 
               
               
                 HEY1 
                 Island 
                 8 
                 80840367 
                 80840374 
                 80840376 
                 80840382 
                 80840385 
               
               
                 HAGH 
                 Shore 
                 16 
                 1814967 
                 1814974 
                 1814978 
                 1815044 
                 1815048 
               
               
                 HAGH 
                 Island 
                 16 
                 1816837 
                 1816840 
                 1816843 
                 1816846 
                 1816848 
               
               
                 SEMA3C 
                 Shore 
                 7 
                 80387012 
                 80387355 
                 80387019 
                 80387340 
                 80387067 
               
               
                 DSCAML1 
                 Shore 
                 11 
                 117170021 
                 117170072 
                 117170149 
                 117170209 
                 117170224 
               
               
                 GPT2 
                 Shore 
                 16 
                 45474293 
                 45474335 
                 45474389 
                 45474480 
                 45474502 
               
               
                 ZNF532 
                 Shore 
                 18 
                 54683963 
                 54683972 
                 54683997 
                 54684040 
                 54684060 
               
               
                   
               
            
           
           
               
            
               
                 Chromosomal coordinates for CG1-CG9 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Gene 
                 Region 
                 CG6 
                 CG7 
                 CG8 
                 CG9 
               
               
                   
                   
               
               
                   
                 SLMO2 
                 Shore 
                 57049937 
                 57049958 
                 57049972 
                 57050013 
               
               
                   
                 SLMO2 
                 Island 
                 57051293 
                 57051299 
                 57051305 
                 57051308 
               
               
                   
                 PCDH9 
                 Shore 
                 66699126 
               
               
                   
                 PCDH9 
                 Island 
                 66702766 
                 66702770 
                 66702776 
                 66702779 
               
               
                   
                 HEY1 
                 Shore 
               
               
                   
                 HEY1 
                 Island 
                 80840389 
                 80840391 
                 80840399 
                 80840409 
               
               
                   
                 HAGH 
                 Shore 
                 1815086 
                 1815091 
                 1815095 
               
               
                   
                 HAGH 
                 Island 
                 1816851 
                 1816868 
                 1816873 
                 1816875 
               
               
                   
                 SEMA3C 
                 Shore 
                 80387071 
                 80387080 
                 80387092 
                 80387102 
               
               
                   
                 DSCAML1 
                 Shore 
                 117170231 
                 117170236 
                 117170239 
                 117170250 
               
               
                   
                 GPT2 
                 Shore 
                 45474508 
                 45474539 
                 45474564 
               
               
                   
                 ZNF532 
                 Shore 
                 54684099 
                 54684127 
                 54684162 
               
               
                   
                   
               
            
           
           
               
            
               
                 Chromosomal coordinates for CG10-CG18 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 Region 
                 Chr 
                 CG10 
                 CG11 
                 CG12 
                 CG13 
                 CG14 
                 CG15 
                 CG16 
                 CG17 
                 CG18 
               
               
                   
               
               
                 SLMO2 
                 Shore 
                 20 
                 57050041 
                 57050045 
                 57050047 
                 57050057 
                 57050099 
                 57050109 
                 57050116 
                 57050141 
                 57050171 
               
               
                 SLMO2 
                 Island 
                 20 
                 57051310 
                 57051317 
                 57051305 
                 57051327 
                 57051329 
                 57051337 
                 57051347 
               
               
                 PCDH9 
                 Shore 
                 13 
               
               
                 PCDH9 
                 Island 
                 13 
                 66702783 
                 66702789 
                 66702798 
                 66702802 
                 66702816 
                 66702825 
                 66702828 
                 66702838 
                 66702841 
               
               
                 HEY1 
                 Shore 
                 8 
               
               
                 HEY1 
                 Island 
                 8 
                 80840425 
                 80840435 
                 80840441 
                 80840446 
               
               
                 HAGH 
                 Shore 
                 16 
               
               
                 HAGH 
                 Island 
                 16 
                 1816895 
                 1816904 
                 1816909 
                 1816913 
                 1816927 
                 1816929 
                 1816933 
                 1816935 
                 1816953 
               
               
                 SEMA3C 
                 Shore 
                 7 
                 80387104 
                 80387107 
                 80387120 
               
               
                 DSCAML1 
                 Shore 
                 11 
                 117170304 
                 117170311 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Primer Sequences and Annealing Temperatures 
               
               
                 Used for Bisulfite Pyrosequencing 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 Nested 
               
               
                   
                   
                   
                   
                 (SEQ 
                 Annealing 
                 annealing 
               
               
                   
                   
                   
                 Sequence 
                 ID 
                 temperature 
                 temperature 
               
               
                 Gene 
                 Region 
                 Primer 
                 (5′→3′) 
                 NO’S) 
                 (° C.) 
                 (° C.) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 SLMO2 
                 Island 
                 Forward 
                 ATAATGAGGTA 
                 4 
                 44 
                   
               
               
                   
                   
                   
                 TAGAGGTTATA 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AACATCTATAT 
                 5 
                   
                   
               
               
                   
                   
                   
                 CAACAAACTAA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-GAGGTTA 
                 6 
                   
                 45 
               
               
                   
                   
                   
                 TATTTGTTTTT 
                   
                   
                   
               
               
                   
                   
                   
                 GTTT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-AACTCTA 
                 7 
                   
                   
               
               
                   
                   
                   
                 CCCAAAAATCA 
                   
                   
                   
               
               
                   
                   
                   
                 AAA 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GGTTTTGTTTT 
                 8 
                   
                   
               
               
                   
                   
                   
                 AGTTTTG 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (R) 
                 CAAAACTAAAA 
                 9 
                   
                   
               
               
                   
                   
                   
                 CAAAACC 
                   
                   
                   
               
               
                   
                 Shore 
                 Forward 
                 GATATAGTAGG 
                 10 
                 49 
                   
               
               
                   
                   
                   
                 TTTTAGGATGT 
                   
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TTACCACACTA 
                 11 
                   
                   
               
               
                   
                   
                   
                 TTTTAATTAAT 
                   
                   
                   
               
               
                   
                   
                   
                 ATAACCT 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 AGGATGTGTTT 
                 12 
                   
                 43 
               
               
                   
                   
                   
                 TATTGAGTATA 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-AAAACCA 
                 13 
                   
                   
               
               
                   
                   
                   
                 TTTATATTTTT 
                   
                   
                   
               
               
                   
                   
                   
                 AAAACT 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 TGTTTTATTGA 
                 14 
                   
                   
               
               
                   
                   
                   
                 GTATAAATG 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (F) 
                 GTGGTTTATAT 
                 15 
                   
                   
               
               
                   
                   
                   
                 TTGTAATTT 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 GAATTATTTGA 
                 16 
                   
                   
               
               
                   
                   
                   
                 GGTTAGGTG 
                   
                   
                   
               
               
                   
                   
                 Scquencing4 (F) 
                 TGATTAATATG 
                 17 
                   
                   
               
               
                   
                   
                   
                 GTGAAATTT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing5 (F) 
                 TTAAAAATATA 
                 18 
                   
                   
               
               
                   
                   
                   
                 AAAATTAGT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing6 (F) 
                 GGAGGTTAAGG 
                 19 
                   
                   
               
               
                   
                   
                   
                 TAGGAGAAT 
                   
                   
                   
               
               
                   
                   
                 Sequencing7 (F) 
                 GTTGTAGTGAG 
                 20 
                   
                   
               
               
                   
                   
                   
                 TTAAGAATA 
                   
                   
                   
               
               
                   
               
               
                 HEY 
                 Island 
                 Forward 
                 GAGGTGATTAT 
                 21 
                 46 
                   
               
               
                   
                   
                   
                 AGGGAGTAT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AACCCTAAAAT 
                 22 
                   
                   
               
               
                   
                   
                   
                 TTTTCTTTTAT 
                   
                   
                   
               
               
                   
                   
                   
                 TC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTTTTGGGGTA 
                 23 
                   
                 41 
               
               
                   
                   
                   
                 GTAATAG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CTAAACA 
                 24 
                   
                   
               
               
                   
                   
                   
                 TCATTAAAAAA 
                   
                   
                   
               
               
                   
                   
                   
                 CTA 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 GGTTTTTTAGG 
                 25 
                   
                   
               
               
                   
                   
                   
                 GAATGTGTT 
                   
                   
                   
               
               
                   
                 Shore 
                 Forward 
                 AAAGAGGTATT 
                 26 
                 49 
                   
               
               
                   
                   
                   
                 ATTATTTATAT 
                   
                   
                   
               
               
                   
                   
                   
                 ATTTTGTGG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TATTAAACTTA 
                 27 
                   
                   
               
               
                   
                   
                   
                 AACCTAAAATT 
                   
                   
                   
               
               
                   
                   
                   
                 TCACATC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GGTAGTTTTAGG 
                 28 
                   
                 45 
               
               
                   
                   
                   
                 AAAATTAGG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-AACTATTA 
                 29 
                   
                   
               
               
                   
                   
                   
                 ATAACCCTAAAT 
                   
                   
                   
               
               
                   
                   
                   
                 CC 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GTATTATTTAAT 
                 30 
                   
                   
               
               
                   
                   
                   
                 TGATTATT 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (F) 
                 ATATTTGTGAAT 
                 31 
                   
                   
               
               
                   
                   
                   
                 TTGAGATT 
                   
                   
                   
               
               
                   
                   
                 Sequeneing3 (F) 
                 TTGGGGTTGGTA 
                 32 
                   
                   
               
               
                   
                   
                   
                 AATGTAGG 
                   
                   
                   
               
               
                   
                   
                 Sequencing4 (F) 
                 AATGAGATTTAA 
                 33 
                   
                   
               
               
                   
                   
                   
                 TTTATTAG 
                   
                   
                   
               
               
                   
               
               
                 HAGH 
                 Island 
                 Forward 
                 TAGGTTTGGTTT 
                 34 
                 46 
                   
               
               
                   
                   
                   
                 TGTTTATTTAG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 CAATAACCTAAA 
                 35 
                   
                   
               
               
                   
                   
                   
                 TACTACCATAAT 
                   
                   
                   
               
               
                   
                   
                   
                 T 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-GTTGTTT 
                 36 
                   
                 44 
               
               
                   
                   
                   
                 AGGATTGTAAA 
                   
                   
                   
               
               
                   
                   
                   
                 ATAT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-AAAAAAA 
                 37 
                   
                   
               
               
                   
                   
                   
                 CCAACTACCTC 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 TTGTTTTTAGT 
                 38 
                   
                   
               
               
                   
                   
                   
                 TAATTAG 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (F) 
                 GTATAGTGGATT 
                 39 
                   
                   
               
               
                   
                   
                   
                 TTTGGAGGT 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (R) 
                 CTAATTAACTAA 
                 40 
                   
                   
               
               
                   
                   
                   
                 AAACAA 
                   
                   
                   
               
               
                   
                   
                 Sequencing4 (R) 
                 ACCTCCAAAAAT 
                 41 
                   
                   
               
               
                   
                   
                   
                 CCACTATAC 
                   
                   
                   
               
               
                   
                 Shore 
                 Forward 
                 AAGGAGTATAAT 
                 42 
                 49 
                   
               
               
                   
                   
                   
                 AAGTAGAGTGTG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AAAACACCTCCC 
                 43 
                   
                   
               
               
                   
                   
                   
                 TAAATTATCAA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTAGAAGGGTTG 
                 44 
                   
                 48 
               
               
                   
                   
                   
                 TGATAGGAT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CCTCCCTAA 
                 45 
                   
                   
               
               
                   
                   
                   
                 ATTATCAACTTC 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GAAGGGTTGTG 
                 46 
                   
                   
               
               
                   
                   
                   
                 ATAGGATTT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing2 (F) 
                 ATAAATAAAAA 
                 47 
                   
                   
               
               
                   
                   
                   
                 TATTGTTTA 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 ATTTTAGTATT 
                 48 
                   
                   
               
               
                   
                   
                   
                 TTGGGAGGT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing4 (F) 
                 AAATATAAAAA 
                 49 
                   
                   
               
               
                   
                   
                   
                 TTAGTTGGG 
                   
                   
                   
               
               
                   
                   
                 Sequencing5 (F) 
                 GGAGGTTGAGG 
                 50 
                   
                   
               
               
                   
                   
                   
                 TAGGAGATT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing6 (F) 
                 AGGTAGAGGTT 
                 51 
                   
                   
               
               
                   
                   
                   
                 GTAGTGAGT 
                   
                   
                   
               
               
                   
               
               
                 PCDH9 
                 Island 
                 Forward 
                 GTTGATTGTTT 
                 52 
                 45 
                   
               
               
                   
                   
                   
                 TTTAGTTTTTTT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 CCCAACCCAAAA 
                 53 
                   
                   
               
               
                   
                   
                   
                 ATAACTATA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-AAATTTGA 
                 54 
                   
                 49 
               
               
                   
                   
                   
                 TTTTGGTTTTAG 
                   
                   
                   
               
               
                   
                   
                   
                 GAGA 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-ACTCCCCC 
                 55 
                   
                   
               
               
                   
                   
                   
                 ATCTATACATTT 
                   
                   
                   
               
               
                   
                   
                   
                 TAA 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GTATTGAGTATG 
                 56 
                   
                   
               
               
                   
                   
                   
                 TTTTGTAGGGTT 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (R) 
                 CTTCACTTAACA 
                 57 
                   
                   
               
               
                   
                   
                   
                 AAAAAATAT 
                   
                   
                   
               
               
                   
                 Shore 
                 Forward 
                 GAAAATGATTAT 
                 58 
                 49 
                   
               
               
                   
                   
                   
                 GAGTAAATTTGG 
                   
                   
                   
               
               
                   
                   
                   
                 G 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 CTTAAAAATAAA 
                 59 
                   
                   
               
               
                   
                   
                   
                 AATAACAACCCA 
                   
                   
                   
               
               
                   
                   
                   
                 CC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GAGTAAATTTGG 
                 60 
                   
                 48 
               
               
                   
                   
                   
                 GGTTATTGT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CCAATTTT 
                 61 
                   
                   
               
               
                   
                   
                   
                 CAACCAACCTAT 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 AGAATAGTAATA 
                 62 
                   
                   
               
               
                   
                   
                   
                 ATTATAGT 
                   
                   
                   
               
               
                   
                   
                 Scquencing2 (F) 
                 TAGTTATTGTAA 
                 63 
                   
                   
               
               
                   
                   
                   
                 AAATGAAT 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 TTGTTAAAATTT 
                 64 
                   
                   
               
               
                   
                   
                   
                 TTGTTTTT 
                   
                   
                   
               
               
                   
                   
                 Scqucncing4 (F) 
                 TAGTTGTTAAGT 
                 65 
                   
                   
               
               
                   
                   
                   
                 ATAATTTA 
                   
                   
                   
               
               
                   
               
               
                 SEMA3C 
                 Shore 
                 Forward 
                 TGTATTTTTAGT 
                 66 
                 49 
                   
               
               
                   
                   
                   
                 AGAGATAGGGTT 
                   
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TCTATTAACATA 
                 67 
                   
                   
               
               
                   
                   
                   
                 ACTCAAAACAAC 
                   
                   
                   
               
               
                   
                   
                   
                 C 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 TTAGTAGAGATA 
                 68 
                   
                 46 
               
               
                   
                   
                   
                 GGGTTAGG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CAAAACAA 
                 69 
                   
                   
               
               
                   
                   
                   
                 CCTCTCCACATA 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GATTTTTTGATT 
                 70 
                   
                   
               
               
                   
                   
                   
                 TAATGGTT 
                   
                   
                   
               
               
                   
                   
                 Scquencing2 (F) 
                 TTAAAATAGGTT 
                 71 
                   
                   
               
               
                   
                   
                   
                 AAGATAAA 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 TAATTTTGTTGA 
                 72 
                   
                   
               
               
                   
                   
                   
                 TTTTTTTA 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 TATTTTTAAA 
                 7S 
                   
                   
               
               
                   
                   
                   
                 TATAATTATA 
                   
                   
                   
               
               
                   
               
               
                 DSCAML1 
                 Shore 
                 Forward 
                 TAGATATTGAATA 
                 74 
                 49 
                   
               
               
                   
                   
                   
                 GAATGTTGGAGA 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 ATTATTTCCATT 
                 75 
                   
                   
               
               
                   
                   
                   
                 CCTCTCAAAATA 
                   
                   
                   
               
               
                   
                   
                   
                 C 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 AGAATGTTGGAG 
                 76 
                   
                 45 
               
               
                   
                   
                   
                 ATTTTTTTAATG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CCTTTTTT 
                 77 
                   
                   
               
               
                   
                   
                   
                 TTATAATACCTA 
                   
                   
                   
               
               
                   
                   
                   
                 AACT 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 AGATTTTTTTAA 
                 78 
                   
                   
               
               
                   
                   
                   
                 TGTTTTGA 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (F) 
                 GAAGAATTATGA 
                 79 
                   
                   
               
               
                   
                   
                   
                 GTTTTTAT 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 GAAAATAGGAAT 
                 80 
                   
                   
               
               
                   
                   
                   
                 TTTAGTGT 
                   
                   
                   
               
               
                   
                   
                 Sequencing4 (F) 
                 AGGTAATATAGA 
                 81 
                   
                   
               
               
                   
                   
                   
                 TGTTGGTA 
                   
                   
                   
               
               
                   
                   
                 Sequencing5 (F) 
                 TAAGGTAGTTAT 
                 82 
                   
                   
               
               
                   
                   
                   
                 TGGAGATT 
                   
                   
                   
               
               
                   
               
               
                 GPT2 
                 Shore 
                 Forward 
                 ATTGGGGAAGAT 
                 83 
                 49 
                   
               
               
                   
                   
                   
                 TTTTATTTAGAG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 CTAAATCCCAAA 
                 84 
                   
                   
               
               
                   
                   
                   
                 TTCTCCATATAC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 AGATTGAATATT 
                 85 
                   
                 44 
               
               
                   
                   
                   
                 TGGTTATTAAG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CTCTAAAA 
                 86 
                   
                   
               
               
                   
                   
                   
                 TCCTTCCCCTTA 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 ATTTAGTGTAGA 
                 87 
                   
                   
               
               
                   
                   
                   
                 TAAAGGTG 
                   
                   
                   
               
               
                   
                   
                 Scqucncing2 (F) 
                 GAGTTTAAATAA 
                 88 
                   
                   
               
               
                   
                   
                   
                 TTTTTTAG 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 GGAATATTTAAA 
                 89 
                   
                   
               
               
                   
                   
                   
                 GATATTTT 
                   
                   
                   
               
               
                   
                   
                 Sequencing4 (F) 
                 TAGGTGTTATTT 
                 90 
                   
                   
               
               
                   
                   
                   
                 TGATTTTA 
                   
                   
                   
               
               
                   
                   
                 Scquencing5 (F) 
                 AAATTTAGTTAA 
                 91 
                   
                   
               
               
                   
                   
                   
                 GTAGTGTA 
                   
                   
                   
               
               
                   
               
               
                 ZNF532 
                 Shore 
                 Forward 
                 TTTAGAGTGGAG 
                 92 
                 49 
                   
               
               
                   
                   
                   
                 AAGAAATGTT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 ATATTCCACATT 
                 93 
                   
                   
               
               
                   
                   
                   
                 AAACATATACCA 
                   
                   
                   
               
               
                   
                   
                   
                 C 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTTTAATGGGAT 
                 94 
                   
                 46 
               
               
                   
                   
                   
                 TAGAGTGATTT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-ATAAAAAA 
                 95 
                   
                   
               
               
                   
                   
                   
                 CCTTTCAAATTA 
                   
                   
                   
               
               
                   
                   
                   
                 ACAC 
                   
                   
                   
               
               
                   
                   
                 Sequencing1 (F) 
                 GTGATTTTATGA 
                 96 
                   
                   
               
               
                   
                   
                   
                 TGGTATTG 
                   
                   
                   
               
               
                   
                   
                 Sequencing2 (F) 
                 GAGTTAGGTTTG 
                 97 
                   
                   
               
               
                   
                   
                   
                 GAAGGAAG 
                   
                   
                   
               
               
                   
                   
                 Sequencing3 (F) 
                 ATGTGTTGTTTT 
                 98 
                   
                   
               
               
                   
                   
                   
                 GTATAAGA 
                   
                   
                   
               
               
                   
                   
                 Sequencing4 (F) 
                 AAGGAAGGGTTT 
                 99 
                   
                   
               
               
                   
                   
                   
                 TATTAAAT 
                   
                   
                   
               
               
                   
               
               
                 DLX5C 
                 Shore 
                 Forward 
                 TATTTAGGGTTA 
                 100 
                 48 
                   
               
               
                   
                   
                   
                 TTTGGTTTTTTT 
                   
                   
                   
               
               
                   
                   
                   
                 T 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AACCTAACTCCC 
                 101 
                   
                   
               
               
                   
                   
                   
                 TACCCACTTATC 
                   
                   
                   
               
               
                   
                   
                   
                 T 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-GGATTGTA 
                 102 
                   
                 43 
               
               
                   
                   
                   
                 TTAGAAAAATAT 
                   
                   
                   
               
               
                   
                   
                   
                 AGT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 ACCCATATTTCC 
                 103 
                   
                   
               
               
                   
                   
                   
                 CTCCTAT 
                   
                   
                   
               
               
                   
                   
                 Sequencing (R) 
                 CTACAACTCTAT 
                 104 
                   
                   
               
               
                   
                   
                   
                 TTACCC 
                   
                   
                   
               
               
                   
               
               
                 ERICH1 
                 Shore 
                 Forward 
                 TATTTTATTGTG 
                 105 
                 51 
                   
               
               
                   
                   
                   
                 GGAGTTTTTGGA 
                   
                   
                   
               
               
                   
                   
                   
                 G 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AATAATCACATT 
                 106 
                   
                   
               
               
                   
                   
                   
                 TCTCACTTTTAC 
                   
                   
                   
               
               
                   
                   
                   
                 CACTA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 TGGGAGTTTTTG 
                 107 
                   
                 42 
               
               
                   
                   
                   
                 GAGTATAGT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 TATATTTACCTA 
                 108 
                   
                   
               
               
                   
                   
                   
                 TATTCCTATCT 
                   
                   
                   
               
               
                   
                   
                 Sequencing (R) 
                 AATAAAATACAT 
                 109 
                   
                   
               
               
                   
                   
                   
                 TTATTATCATT 
                   
                   
                   
               
               
                   
               
               
                 FAM70B 
                 Island 
                 Forward 
                 TTTTGTGTTTT 
                 110 
                 52 
                   
               
               
                   
                   
                   
                 GTTGTGGTGTG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 CTAACTCCAAA 
                 111 
                   
                   
               
               
                   
                   
                   
                 CTCCAAAACCA 
                   
                   
                   
               
               
                   
                   
                   
                 TTA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GGAAATGAGAT 
                 112 
                   
                 46 
               
               
                   
                   
                   
                 TTATTGAGAG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CTCTCCT 
                 113 
                   
                   
               
               
                   
                   
                   
                 TCTATTACAAC 
                   
                   
                   
               
               
                   
                   
                   
                 TAA 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 TAGTTATTGGT 
                 114 
                   
                   
               
               
                   
                   
                   
                 AATTTTTAG 
                   
                   
                   
               
               
                   
               
               
                 SLITRK1 
                 Shore 
                 Forward 
                 TTGATTTTGAT 
                 115 
                 48 
                   
               
               
                   
                   
                   
                 TTGTTAGTTGT 
                   
                   
                   
               
               
                   
                   
                   
                 TTG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TATTCCAATAT 
                 116 
                   
                   
               
               
                   
                   
                   
                 ATACCCATCAC 
                   
                   
                   
               
               
                   
                   
                   
                 CC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-GGGGTTT 
                 117 
                   
                 45 
               
               
                   
                   
                   
                 AGGAGTAAAGG 
                   
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 CTACCCTATAA 
                 118 
                   
                   
               
               
                   
                   
                   
                 AAAAATCTTAA 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Sequencing (R) 
                 ATTCCCAAAAA 
                 119 
                   
                   
               
               
                   
                   
                   
                 TACCCTAAT 
                   
                   
                   
               
               
                   
               
               
                 LRFN5 
                 Shore 
                 Forward 
                 TTGTTGTGGAG 
                 120 
                 48 
                   
               
               
                   
                   
                   
                 GAGTTTGTTAG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TCCAACCTACT 
                 121 
                   
                   
               
               
                   
                   
                   
                 CCTTATAAATC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 TGGTTTGTATG 
                 122 
                   
                 49 
               
               
                   
                   
                   
                 AAAGGGAATAT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CCTACTC 
                 123 
                   
                   
               
               
                   
                   
                   
                 CTTATAAATCA 
                   
                   
                   
               
               
                   
                   
                   
                 AAACACC 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 TTTAGTTGTAT 
                 124 
                   
                   
               
               
                   
                   
                   
                 TGTTTT 
                   
                   
                   
               
               
                   
               
               
                 FEZF2 
                 Shore 
                 Forward 
                 GTGTGGTTAGA 
                 125 
                 50 
                   
               
               
                   
                   
                   
                 GGTATAAGTAG 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 TCAACCCTCTC 
                 126 
                   
                   
               
               
                   
                   
                   
                 AAAACTTATTC 
                   
                   
                   
               
               
                   
                   
                   
                 CTA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTAGAGGGAAG 
                 127 
                   
                 49 
               
               
                   
                   
                   
                 AAAAGATTTTT 
                   
                   
                   
               
               
                   
                   
                   
                 TTT 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-CCCAATC 
                 128 
                   
                   
               
               
                   
                   
                   
                 CTCCCCCTTTC 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 TTGTAGATTAT 
                 129 
                   
                   
               
               
                   
                   
                   
                 TTTATTTG 
                   
                   
                   
               
               
                   
               
               
                 TMEM14A 
                 Island 
                 Forward 
                 TGGGTGGGTGT 
                 130 
                 54 
                   
               
               
                   
                   
                   
                 AGATATTTTGT 
                   
                   
                   
               
               
                   
                   
                   
                 TAT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 ACAATCCTACA 
                 131 
                   
                   
               
               
                   
                   
                   
                 CACACAAACCT 
                   
                   
                   
               
               
                   
                   
                   
                 TTA 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 Bio-TAGTGAA 
                 132 
                   
                 48 
               
               
                   
                   
                   
                 AGTTTTGGGAA 
                   
                   
                   
               
               
                   
                   
                   
                 ATTTA 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 CTACACACACA 
                 133 
                   
                   
               
               
                   
                   
                   
                 AACCTTTAATA 
                   
                   
                   
               
               
                   
                   
                   
                 A 
                   
                   
                   
               
               
                   
                   
                 Sequencing (R) 
                 ATTCATTTTAA 
                 134 
                   
                   
               
               
                   
                   
                   
                 AAAATAATCC 
                   
                   
                   
               
               
                   
               
               
                 TMEPAI 
                 Shore 
                 Forward 
                 TATTAATTAAA 
                 135 
                 49 
                   
               
               
                   
                   
                   
                 TTGTTTTTAGG 
                   
                   
                   
               
               
                   
                   
                   
                 AAGGTAAT 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AAATTTACATA 
                 136 
                   
                   
               
               
                   
                   
                   
                 AAACCACAACA 
                   
                   
                   
               
               
                   
                   
                   
                 AAC 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTTTTTAGGAA 
                 137 
                   
                 45 
               
               
                   
                   
                   
                 GGTAATTAGAA 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 Bio-TACAAAA 
                 138 
                   
                   
               
               
                   
                   
                   
                 ACTTACCAAAT 
                   
                   
                   
               
               
                   
                   
                   
                 CTATAT 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 AAATTTTAAGA 
                 139 
                   
                   
               
               
                   
                   
                   
                 AGTTAGTA 
                   
                   
                   
               
               
                   
               
               
                 HOXA3 
                 Island 
                 Forward 
                 GATTAATGAGT 
                 140 
                 48 
                   
               
               
                   
                   
                   
                 TATAGAGAGAT 
                   
                   
                   
               
               
                   
                   
                   
                 GTTG 
                   
                   
                   
               
               
                   
                   
                 Reverse 
                 AAGGAGTTAAA 
                 141 
                   
                   
               
               
                   
                   
                   
                 AGTTTTTGGAG 
                   
                   
                   
               
               
                   
                   
                 Nested forward 
                 GTTTAGGTTTT 
                 142 
                   
                 43 
               
               
                   
                   
                   
                 TTATTTTATAA 
                   
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
                   
               
               
                   
                   
                 Nested reverse 
                 TAAGATTTGGT 
                 143 
                   
                   
               
               
                   
                   
                   
                 GAGGGTTTGT 
                   
                   
                   
               
               
                   
                   
                 Sequencing (F) 
                 GGGTGATTTAT 
                 144 
                   
                   
               
               
                   
                   
                   
                 GAA 
               
               
                   
               
               
                 Bio = 5′ biotin added; F = forward; R = reverse 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Real time quantitative RT-PCR assays 
               
            
           
           
               
               
               
            
               
                   
                 Gene 
                 Assay ID (Applied Biosystems) 
               
               
                   
                   
               
               
                   
                 FZD3 
                 Hs00184043_m1 
               
               
                   
                 RBM38 
                 Hs00766686_m1 
               
               
                   
                 NDN 
                 Hs00267349_s1 
               
               
                   
                 TRAF1 
                 Hs00194638_m1 
               
               
                   
                 ZNF804A 
                 Hs00290118_s1 
               
               
                   
                 CHRM2 
                 Hs00265208_s1 
               
               
                   
                 NQO1 
                 Hs00168547_m1 
               
               
                   
                 SEMA3C 
                 Hs00170762_m1 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 Regions with tissue-specific differential methylation (T-DMRs) at a FDR of 5%. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 tissue 
                   
                   
                   
               
               
                 chr 
                 start 
                 end 
                 fdr 
                 Varying 
                 brainM 
                 liverM 
                 spleenM 
               
               
                   
               
               
                 chr1 
                 143786173 
                 143787603 
                 0 
                 brain 
                 −0.11535 
                 1.487259 
                 1.302311 
               
               
                 chr1 
                 8009359 
                 8011113 
                 0 
                 liver 
                 1.299418 
                 −0.0514 
                 1.426635 
               
               
                 chr10 
                 101831054 
                 101831872 
                 0 
                 liver 
                 1.292584 
                 −0.05296 
                 1.304799 
               
               
                 chr12 
                 131467604 
                 131472462 
                 0 
                 brain 
                 0.26132 
                 1.456655 
                 1.679197 
               
               
                 chr12 
                 6531994 
                 6532981 
                 0 
                 All 
                 −0.20912 
                 1.254775 
                 0.874488 
               
               
                 chr14 
                 23089148 
                 23090035 
                 0 
                 All 
                 −0.63109 
                 1.535749 
                 1.192863 
               
               
                 chr14 
                 50629706 
                 50630173 
                 0 
                 All 
                 −0.08017 
                 1.408726 
                 1.106452 
               
               
                 chr14 
                 59165574 
                 59166710 
                 0 
                 brain 
                 −0.14155 
                 1.252699 
                 1.205902 
               
               
                 chr15 
                 75709049 
                 75710128 
                 0 
                 brain 
                 −0.15474 
                 1.309527 
                 1.226063 
               
               
                 chr15 
                 91163167 
                 91164726 
                 0 
                 All 
                 −0.47387 
                 1.249181 
                 0.967742 
               
               
                 chr16 
                 45472725 
                 45475365 
                 0 
                 liver 
                 1.345268 
                 −0.04038 
                 1.356521 
               
               
                 chr16 
                 45477675 
                 45478565 
                 0 
                 All 
                 −0.55643 
                 0.63018 
                 1.629881 
               
               
                 chr18 
                 54682827 
                 54684488 
                 0 
                 brain 
                 −0.46482 
                 1.381573 
                 1.207633 
               
               
                 chr2 
                 54538538 
                 54540625 
                 0 
                 All 
                 −0.28043 
                 1.191245 
                 0.59945 
               
               
                 chr20 
                 60184636 
                 60188417 
                 0 
                 liver 
                 1.335582 
                 −0.15525 
                 1.454903 
               
               
                 chr4 
                 99796292 
                 99798038 
                 0 
                 All 
                 −0.53255 
                 1.000455 
                 0.477587 
               
               
                 chr5 
                 98138988 
                 98139704 
                 0 
                 brain 
                 0.361833 
                 1.754281 
                 1.493639 
               
               
                 chr8 
                 17314239 
                 17314991 
                 0 
                 brain 
                 −0.11832 
                 1.481885 
                 1.356334 
               
               
                 chr8 
                 75425908 
                 75426276 
                 0 
                 All 
                 −0.3947 
                 1.254908 
                 0.888546 
               
               
                 chrX 
                 144713386 
                 144714243 
                 0 
                 brain 
                 −0.03791 
                 1.36192 
                 1.560882 
               
               
                 chrX 
                 53131580 
                 53132161 
                 0 
                 brain 
                 0.355145 
                 1.795164 
                 1.815183 
               
               
                 chr17 
                 73467744 
                 73468595 
                 1.72E−14 
                 All 
                 0.021405 
                 1.358955 
                 1.058227 
               
               
                 chr15 
                 35173578 
                 35174577 
                 1.73E−14 
                 All 
                 −0.25443 
                 1.220796 
                 0.644358 
               
               
                 chr7 
                 129916095 
                 129916949 
                 2.55E−14 
                 All 
                 0.046312 
                 1.436957 
                 0.996807 
               
               
                 chr1 
                 158637654 
                 158638754 
                 2.71E−14 
                 brain 
                 −0.28314 
                 1.130432 
                 0.847571 
               
               
                 chr11 
                 64877881 
                 64878384 
                 5.10E−14 
                 All 
                 0.041802 
                 1.412251 
                 1.04274 
               
               
                 chr6 
                 97479869 
                 97480719 
                 8.58E−14 
                 brain 
                 −0.17882 
                 1.149061 
                 1.019161 
               
               
                 chr20 
                 6462584 
                 6463175 
                 1.57E−13 
                 brain 
                 −0.07902 
                 1.303117 
                 1.070685 
               
               
                 chr17 
                 71959149 
                 71959442 
                 1.79E−13 
                 All 
                 −0.07652 
                 1.36918 
                 0.89536 
               
               
                 chr17 
                 35473766 
                 35475501 
                 2.38E−13 
                 All 
                 −0.51389 
                 0.699964 
                 0.36019 
               
               
                 chr7 
                 130438711 
                 130440952 
                 2.63E−13 
                 All 
                 −0.13901 
                 1.122755 
                 0.781425 
               
               
                 chr18 
                 51240890 
                 51242290 
                 3.03E−13 
                 brain 
                 −0.29669 
                 1.01559 
                 0.812538 
               
               
                 chr14 
                 52687631 
                 52688222 
                 3.07E−13 
                 All 
                 −0.40997 
                 0.899323 
                 0.121039 
               
               
                 chr19 
                 53707072 
                 53707611 
                 7.25E−13 
                 brain 
                 −0.58951 
                 0.757836 
                 0.547046 
               
               
                 chr1 
                 242283486 
                 242284310 
                 8.08E−13 
                 brain 
                 0.197052 
                 1.546314 
                 1.564309 
               
               
                 chr22 
                 44837327 
                 44840079 
                 9.71E−13 
                 brain 
                 −0.02283 
                 1.364865 
                 1.280148 
               
               
                 chr22 
                 26520905 
                 26522055 
                 9.74E−13 
                 brain 
                 −0.08032 
                 1.409407 
                 1.409504 
               
               
                 chr12 
                 111302662 
                 111303654 
                 1.10E−12 
                 brain 
                 0.036707 
                 1.361237 
                 1.307891 
               
               
                 chr16 
                 17468105 
                 17468795 
                 1.32E−12 
                 All 
                 −0.01385 
                 1.030508 
                 1.451115 
               
               
                 chr6 
                 53768814 
                 53769599 
                 1.33E−12 
                 brain 
                 0.134246 
                 1.283679 
                 1.070607 
               
               
                 chr12 
                 121944796 
                 121946259 
                 1.42E−12 
                 All 
                 −0.55677 
                 0.652273 
                 −0.04003 
               
               
                 chr4 
                 76775030 
                 76775602 
                 1.75E−12 
                 brain 
                 0.121772 
                 1.391647 
                 1.250962 
               
               
                 chr10 
                 11089463 
                 11090071 
                 2.05E−12 
                 brain 
                 0.0384 
                 1.278444 
                 1.277885 
               
               
                 chr19 
                 12974645 
                 12975430 
                 2.81E−12 
                 brain 
                 0.058949 
                 1.312149 
                 1.366242 
               
               
                 chr9 
                 137121252 
                 137121872 
                 3.27E−12 
                 brain 
                 0.257197 
                 1.567195 
                 1.364371 
               
               
                 chr3 
                 187560575 
                 187561467 
                 3.59E−12 
                 All 
                 −0.06283 
                 1.222911 
                 0.556389 
               
               
                 chr13 
                 43257042 
                 43257653 
                 4.49E−12 
                 brain 
                 0.003724 
                 1.270532 
                 1.252464 
               
               
                 chr14 
                 23083610 
                 23084323 
                 4.84E−12 
                 brain 
                 0.332277 
                 1.600948 
                 1.536168 
               
               
                 chr20 
                 4616137 
                 4616745 
                 5.79E−12 
                 All 
                 −0.33653 
                 0.970823 
                 0.639435 
               
               
                 chr18 
                 72330871 
                 72331443 
                 6.11E−12 
                 All 
                 0.090288 
                 1.251749 
                 0.784134 
               
               
                 chr7 
                 75386078 
                 75389998 
                 6.67E−12 
                 liver 
                 1.552091 
                 0.424268 
                 1.543758 
               
               
                 chr16 
                 30361878 
                 30364176 
                 7.04E−12 
                 liver 
                 1.264842 
                 −0.02377 
                 1.218326 
               
               
                 chr1 
                 234916923 
                 234918037 
                 7.40E−12 
                 brain 
                 0.188523 
                 1.354653 
                 1.349526 
               
               
                 chr1 
                 227542393 
                 227543223 
                 8.16E−12 
                 brain 
                 0.301546 
                 1.554823 
                 1.484626 
               
               
                 chr9 
                 111443165 
                 111443953 
                 9.23E−12 
                 All 
                 −0.30158 
                 0.969521 
                 0.313406 
               
               
                 chr21 
                 42514640 
                 42515749 
                 9.51E−12 
                 All 
                 0.229328 
                 1.50122 
                 1.077787 
               
               
                 chr21 
                 25934681 
                 25935782 
                 9.57E−12 
                 brain 
                 −0.47751 
                 0.721757 
                 0.472824 
               
               
                 chr19 
                 58297027 
                 58297933 
                 1.01E−11 
                 All 
                 −0.41847 
                 0.779032 
                 0.344519 
               
               
                 chrX 
                 48937108 
                 48937860 
                 1.08E−11 
                 brain 
                 0.388972 
                 1.581553 
                 1.611601 
               
               
                 chr1 
                 33418284 
                 33418931 
                 1.11E−11 
                 All 
                 0.173928 
                 1.468768 
                 0.907082 
               
               
                 chr4 
                 21557703 
                 21559151 
                 1.75E−11 
                 brain 
                 0.093552 
                 1.124707 
                 1.26124 
               
               
                 chr17 
                 55509863 
                 55510786 
                 2.04E−11 
                 All 
                 −0.59336 
                 0.510877 
                 −0.04011 
               
               
                 chr21 
                 45713907 
                 45716550 
                 2.04E−11 
                 liver 
                 0.993849 
                 −0.02669 
                 1.158456 
               
               
                 chr2 
                 100303365 
                 100304155 
                 2.09E−11 
                 brain 
                 0.079216 
                 1.422576 
                 1.363524 
               
               
                 chr2 
                 9684653 
                 9686112 
                 2.40E−11 
                 brain 
                 0.168387 
                 1.319339 
                 1.180425 
               
               
                 chr13 
                 66697473 
                 66700370 
                 2.92E−11 
                 brain 
                 −0.11815 
                 1.067169 
                 1.241919 
               
               
                 chr8 
                 120290407 
                 120291436 
                 3.22E−11 
                 All 
                 0.464379 
                 −0.30417 
                 1.031852 
               
               
                 chr17 
                 63963603 
                 63964386 
                 3.36E−11 
                 brain 
                 −0.35063 
                 0.832736 
                 0.572111 
               
               
                 chr5 
                 16236252 
                 16237106 
                 3.62E−11 
                 All 
                 1.603336 
                 0.431418 
                 1.063083 
               
               
                 chr15 
                 27346324 
                 27347653 
                 3.86E−11 
                 brain 
                 0.177365 
                 1.38589 
                 1.150294 
               
               
                 chr8 
                 9795653 
                 9796645 
                 3.97E−11 
                 brain 
                 0.23902 
                 1.519226 
                 1.537175 
               
               
                 chr15 
                 21361048 
                 21361947 
                 4.66E−11 
                 brain 
                 0.131271 
                 1.324638 
                 1.362028 
               
               
                 chr13 
                 43906353 
                 43906790 
                 4.81E−11 
                 brain 
                 0.212522 
                 1.230147 
                 1.332329 
               
               
                 chr20 
                 21536810 
                 21537175 
                 5.08E−11 
                 brain 
                 −0.00897 
                 1.355417 
                 1.309454 
               
               
                 chr6 
                 87918996 
                 87919649 
                 5.11E−11 
                 All 
                 −0.0929 
                 1.110646 
                 0.491515 
               
               
                 chr3 
                 161040187 
                 161040531 
                 5.29E−11 
                 All 
                 −0.12641 
                 1.043576 
                 0.432139 
               
               
                 chr16 
                 85164000 
                 85164607 
                 5.63E−11 
                 spleen 
                 0.046453 
                 0.061563 
                 1.155534 
               
               
                 chr17 
                 44038889 
                 44039760 
                 6.03E−11 
                 All 
                 0.112679 
                 0.619602 
                 1.416283 
               
               
                 chr12 
                 113601482 
                 113602777 
                 6.22E−11 
                 All 
                 −0.20773 
                 0.730495 
                 1.016832 
               
               
                 chr22 
                 19463535 
                 19464248 
                 6.27E−11 
                 All 
                 1.134095 
                 0.037807 
                 1.449567 
               
               
                 chr9 
                 99783345 
                 99784242 
                 6.35E−11 
                 brain 
                 0.238381 
                 1.423687 
                 1.133009 
               
               
                 chr10 
                 104669419 
                 104671001 
                 6.57E−11 
                 brain 
                 −0.0864 
                 0.974036 
                 1.172766 
               
               
                 chr6 
                 52335546 
                 52337567 
                 6.57E−11 
                 brain 
                 −0.14951 
                 0.974944 
                 0.765697 
               
               
                 chr8 
                 80837473 
                 80839800 
                 6.74E−11 
                 brain 
                 −0.13852 
                 1.134604 
                 0.980399 
               
               
                 chr1 
                 200125551 
                 200126951 
                 8.29E−11 
                 All 
                 0.200372 
                 1.343235 
                 1.036733 
               
               
                 chr11 
                 117169663 
                 117170865 
                 8.61E−11 
                 brain 
                 0.036012 
                 1.319412 
                 1.355828 
               
               
                 chr10 
                 88272523 
                 88272784 
                 8.63E−11 
                 All 
                 −0.05095 
                 1.334199 
                 0.977942 
               
               
                 chr3 
                 160966443 
                 160967336 
                 9.13E−11 
                 brain 
                 0.193104 
                 1.277767 
                 1.047332 
               
               
                 chr10 
                 69992084 
                 69993085 
                 9.34E−11 
                 All 
                 −0.03598 
                 1.004592 
                 0.494343 
               
               
                 chr10 
                 72314866 
                 72316425 
                 9.55E−11 
                 liver 
                 1.431814 
                 0.293288 
                 1.410689 
               
               
                 chr5 
                 17272645 
                 17273667 
                 9.66E−11 
                 All 
                 0.335036 
                 1.530197 
                 1.121364 
               
               
                 chr19 
                 57202145 
                 57203221 
                 1.10E−10 
                 brain 
                 −0.19286 
                 1.016431 
                 0.97668 
               
               
                 chr7 
                 139121047 
                 139122912 
                 1.11E−10 
                 All 
                 −0.04716 
                 0.405804 
                 1.070219 
               
               
                 chr11 
                 65816795 
                 65817554 
                 1.27E−10 
                 brain 
                 0.047017 
                 1.183867 
                 1.21434 
               
               
                 chr12 
                 38783038 
                 38784659 
                 1.35E−10 
                 All 
                 0.13847 
                 0.907052 
                 1.253477 
               
               
                 chr18 
                 70271478 
                 70272306 
                 1.48E−10 
                 brain 
                 0.477285 
                 1.616985 
                 1.601359 
               
               
                 chr12 
                 8958831 
                 8959862 
                 1.58E−10 
                 All 
                 −0.41555 
                 0.731955 
                 0.380007 
               
               
                 chr7 
                 35542549 
                 35543379 
                 1.58E−10 
                 liver 
                 1.46152 
                 0.187143 
                 1.513851 
               
               
                 chr22 
                 44856437 
                 44856847 
                 1.75E−10 
                 All 
                 −0.21002 
                 0.964414 
                 0.570562 
               
               
                 chr9 
                 113434267 
                 113436690 
                 1.75E−10 
                 liver 
                 1.110322 
                 −0.06272 
                 1.188455 
               
               
                 chr3 
                 182923902 
                 182926235 
                 1.78E−10 
                 All 
                 −0.28218 
                 0.719899 
                 0.392404 
               
               
                 chr5 
                 87600958 
                 87602603 
                 1.78E−10 
                 brain 
                 0.13372 
                 1.234886 
                 1.288835 
               
               
                 chr22 
                 44840824 
                 44842585 
                 2.07E−10 
                 All 
                 −0.32082 
                 0.854645 
                 0.468445 
               
               
                 chr15 
                 35174959 
                 35175429 
                 2.09E−10 
                 All 
                 −0.02782 
                 1.121221 
                 0.668461 
               
               
                 chr6 
                 32226447 
                 32227133 
                 2.35E−10 
                 brain 
                 −0.12679 
                 1.21501 
                 1.108105 
               
               
                 chr6 
                 24468445 
                 24468955 
                 2.49E−10 
                 All 
                 0.204555 
                 1.450305 
                 1.08434 
               
               
                 chr11 
                 67912958 
                 67914011 
                 2.65E−10 
                 liver 
                 1.672152 
                 0.496634 
                 1.725968 
               
               
                 chr15 
                 49699745 
                 49700848 
                 2.69E−10 
                 All 
                 0.005382 
                 1.100265 
                 0.692709 
               
               
                 chr10 
                 79064134 
                 79065116 
                 2.73E−10 
                 brain 
                 −0.03703 
                 1.057269 
                 0.936404 
               
               
                 chr12 
                 102757515 
                 102758501 
                 2.87E−10 
                 All 
                 0.464408 
                 −0.07212 
                 1.247512 
               
               
                 chr1 
                 244954765 
                 244956165 
                 3.36E−10 
                 All 
                 0.94556 
                 0.057658 
                 1.256526 
               
               
                 chr9 
                 93748388 
                 93749207 
                 3.38E−10 
                 brain 
                 1.558837 
                 0.457913 
                 0.734517 
               
               
                 chr17 
                 69717977 
                 69719999 
                 3.48E−10 
                 brain 
                 0.34338 
                 1.370673 
                 1.257086 
               
               
                 chr5 
                 75735889 
                 75737508 
                 3.59E−10 
                 brain 
                 1.018357 
                 −0.06504 
                 0.153059 
               
               
                 chr14 
                 72427335 
                 72428501 
                 3.61E−10 
                 All 
                 0.110581 
                 1.172443 
                 0.708188 
               
               
                 chr4 
                 108858341 
                 108860158 
                 3.69E−10 
                 All 
                 0.019132 
                 1.121514 
                 0.642438 
               
               
                 chr19 
                 12956890 
                 12957636 
                 3.90E−10 
                 brain 
                 0.317379 
                 1.422033 
                 1.317791 
               
               
                 chr3 
                 135095342 
                 135095599 
                 4.07E−10 
                 All 
                 0.345701 
                 1.547571 
                 1.201468 
               
               
                 chr12 
                 119419408 
                 119420682 
                 4.32E−10 
                 All 
                 −0.45368 
                 0.64277 
                 0.357627 
               
               
                 chr3 
                 194442270 
                 194443491 
                 4.59E−10 
                 brain 
                 0.454163 
                 1.59038 
                 1.582465 
               
               
                 chr18 
                 54678682 
                 54681415 
                 4.71E−10 
                 brain 
                 −0.11259 
                 0.889818 
                 0.731549 
               
               
                 chr10 
                 105441168 
                 105442058 
                 4.95E−10 
                 All 
                 −0.07938 
                 1.057892 
                 0.58793 
               
               
                 chr4 
                 41341411 
                 41342111 
                 5.00E−10 
                 brain 
                 0.015783 
                 1.215938 
                 1.249218 
               
               
                 chr8 
                 80840243 
                 80842031 
                 5.22E−10 
                 All 
                 −0.39056 
                 0.633251 
                 0.035054 
               
               
                 chr20 
                 33336159 
                 33337040 
                 5.25E−10 
                 All 
                 0.496151 
                 −0.19458 
                 1.042875 
               
               
                 chr1 
                 120056929 
                 120057765 
                 5.64E−10 
                 All 
                 0.268229 
                 −0.0413 
                 1.13111 
               
               
                 chr9 
                 102276338 
                 102277457 
                 5.97E−10 
                 brain 
                 0.236111 
                 1.305146 
                 1.117734 
               
               
                 chr19 
                 2651477 
                 2652367 
                 6.88E−10 
                 brain 
                 −0.00437 
                 1.22873 
                 1.134348 
               
               
                 chr11 
                 64858559 
                 64859826 
                 7.01E−10 
                 All 
                 −0.13863 
                 0.855243 
                 0.225677 
               
               
                 chr12 
                 48766660 
                 48767337 
                 7.56E−10 
                 All 
                 0.48622 
                 1.564671 
                 1.166946 
               
               
                 chr14 
                 22839242 
                 22839642 
                 8.19E−10 
                 brain 
                 −0.07093 
                 1.088938 
                 0.895761 
               
               
                 chr12 
                 54406765 
                 54407517 
                 8.73E−10 
                 All 
                 0.079217 
                 1.142971 
                 0.765836 
               
               
                 chr6 
                 71720614 
                 71721830 
                 8.87E−10 
                 All 
                 0.190403 
                 1.277573 
                 0.94305 
               
               
                 chr2 
                 113632025 
                 113632600 
                 9.06E−10 
                 liver 
                 1.312823 
                 0.278355 
                 1.091582 
               
               
                 chr1 
                 152568347 
                 152569153 
                 1.02E−09 
                 brain 
                 0.382712 
                 1.416759 
                 1.180129 
               
               
                 chr19 
                 12986646 
                 12989167 
                 1.02E−09 
                 brain 
                 0.027941 
                 1.171056 
                 0.952401 
               
               
                 chr18 
                 53172450 
                 53172776 
                 1.05E−09 
                 All 
                 −0.18109 
                 0.986896 
                 0.438065 
               
               
                 chr22 
                 42139152 
                 42140849 
                 1.07E−09 
                 brain 
                 0.489183 
                 1.544282 
                 1.580222 
               
               
                 chr8 
                 94999343 
                 95000446 
                 1.08E−09 
                 All 
                 −0.09493 
                 0.967359 
                 0.532637 
               
               
                 chr1 
                 158321798 
                 158322793 
                 1.11E−09 
                 brain 
                 0.259199 
                 1.387606 
                 1.405033 
               
               
                 chr10 
                 45328714 
                 45329270 
                 1.14E−09 
                 brain 
                 0.487386 
                 1.627923 
                 1.640054 
               
               
                 chr4 
                 113519509 
                 113520087 
                 1.17E−09 
                 brain 
                 0.351665 
                 1.428635 
                 1.42591 
               
               
                 chr8 
                 28406277 
                 28406880 
                 1.25E−09 
                 All 
                 0.102019 
                 0.893019 
                 1.44425 
               
               
                 chr6 
                 31697055 
                 31698136 
                 1.31E−09 
                 All 
                 −0.51951 
                 0.524483 
                 0.169974 
               
               
                 chr11 
                 1668090 
                 1669572 
                 1.48E−09 
                 liver 
                 1.099981 
                 0.049418 
                 1.262819 
               
               
                 chr9 
                 20609087 
                 20610219 
                 1.53E−09 
                 All 
                 −0.38654 
                 0.733972 
                 0.290223 
               
               
                 chr4 
                 17390836 
                 17391751 
                 1.57E−09 
                 All 
                 −0.01514 
                 0.610289 
                 1.056951 
               
               
                 chr7 
                 27144976 
                 27145521 
                 1.67E−09 
                 All 
                 0.104066 
                 0.4646 
                 1.284721 
               
               
                 chr13 
                 100100517 
                 100101056 
                 1.69E−09 
                 brain 
                 0.126005 
                 1.270831 
                 1.278393 
               
               
                 chr17 
                 67631765 
                 67632456 
                 1.70E−09 
                 brain 
                 −0.08216 
                 0.965589 
                 1.168482 
               
               
                 chr8 
                 139577318 
                 139577719 
                 1.74E−09 
                 All 
                 0.381754 
                 1.528271 
                 1.20125 
               
               
                 chr6 
                 39302949 
                 39304155 
                 1.76E−09 
                 All 
                 1.220726 
                 0.182266 
                 0.696068 
               
               
                 chr1 
                 159549832 
                 159551072 
                 1.97E−09 
                 All 
                 0.162422 
                 0.860818 
                 1.165009 
               
               
                 chr11 
                 129374246 
                 129376513 
                 2.02E−09 
                 liver 
                 1.442827 
                 0.09828 
                 1.273512 
               
               
                 chr6 
                 26332969 
                 26333508 
                 2.10E−09 
                 All 
                 0.091736 
                 1.175461 
                 0.869038 
               
               
                 chr10 
                 31359338 
                 31360454 
                 2.14E−09 
                 brain 
                 −0.11936 
                 0.893576 
                 0.980227 
               
               
                 chr7 
                 36157999 
                 36159166 
                 2.24E−09 
                 liver 
                 1.386701 
                 0.239862 
                 1.31825 
               
               
                 chr12 
                 116111015 
                 116111629 
                 2.28E−09 
                 All 
                 −0.39965 
                 0.299806 
                 0.840599 
               
               
                 chr12 
                 24945492 
                 24947103 
                 2.30E−09 
                 brain 
                 0.018833 
                 1.077256 
                 0.926808 
               
               
                 chr19 
                 39954301 
                 39955362 
                 2.35E−09 
                 brain 
                 0.084007 
                 1.085292 
                 0.991353 
               
               
                 chr10 
                 124212667 
                 124215516 
                 2.40E−09 
                 brain 
                 0.203019 
                 1.299387 
                 1.287902 
               
               
                 chr22 
                 36999241 
                 36999534 
                 2.42E−09 
                 All 
                 −0.30703 
                 0.886854 
                 0.445371 
               
               
                 chr5 
                 72829082 
                 72829798 
                 2.47E−09 
                 All 
                 −0.12689 
                 0.443145 
                 0.969204 
               
               
                 chr2 
                 42647983 
                 42648909 
                 2.54E−09 
                 All 
                 0.059632 
                 1.131059 
                 0.652138 
               
               
                 chr5 
                 108090358 
                 108091228 
                 2.54E−09 
                 All 
                 0.017378 
                 1.041888 
                 0.707126 
               
               
                 chr2 
                 16071365 
                 16072112 
                 2.58E−09 
                 All 
                 0.337041 
                 1.347634 
                 0.952726 
               
               
                 chr10 
                 105031159 
                 105031629 
                 2.62E−09 
                 All 
                 −0.0494 
                 0.688734 
                 1.016566 
               
               
                 chr19 
                 51170609 
                 51171407 
                 2.74E−09 
                 brain 
                 0.264918 
                 1.321571 
                 1.394371 
               
               
                 chr4 
                 120029760 
                 120030128 
                 2.89E−09 
                 All 
                 −0.27772 
                 0.816238 
                 0.511608 
               
               
                 chr13 
                 107664610 
                 107665176 
                 2.98E−09 
                 All 
                 −0.05834 
                 1.072254 
                 0.649981 
               
               
                 chr1 
                 206056315 
                 206056820 
                 3.15E−09 
                 brain 
                 0.066974 
                 1.098728 
                 1.003981 
               
               
                 chr8 
                 26207367 
                 26208013 
                 3.17E−09 
                 brain 
                 0.038493 
                 1.160728 
                 0.947717 
               
               
                 chr13 
                 112746460 
                 112748715 
                 3.18E−09 
                 brain 
                 0.427857 
                 1.380589 
                 1.457585 
               
               
                 chr2 
                 74585982 
                 74586242 
                 3.20E−09 
                 liver 
                 1.767917 
                 0.640233 
                 1.667118 
               
               
                 chr12 
                 7175952 
                 7176212 
                 3.28E−09 
                 All 
                 −0.01499 
                 1.1523 
                 0.849905 
               
               
                 chr1 
                 109626152 
                 109626919 
                 3.33E−09 
                 brain 
                 −0.04827 
                 0.99007 
                 0.876846 
               
               
                 chr20 
                 23291758 
                 23292447 
                 3.49E−09 
                 All 
                 −0.321 
                 0.800623 
                 0.294726 
               
               
                 chr4 
                 166520211 
                 166521230 
                 3.50E−09 
                 brain 
                 0.1225 
                 1.28178 
                 1.22046 
               
               
                 chr21 
                 39678541 
                 39679533 
                 3.52E−09 
                 liver 
                 1.326263 
                 0.256805 
                 1.372241 
               
               
                 chr5 
                 36278172 
                 36279450 
                 3.64E−09 
                 liver 
                 0.870676 
                 0.007346 
                 1.103939 
               
               
                 chrX 
                 53466762 
                 53467199 
                 3.82E−09 
                 All 
                 −0.89696 
                 0.218855 
                 −0.22092 
               
               
                 chr2 
                 48611532 
                 48612389 
                 3.92E−09 
                 All 
                 −0.04989 
                 0.995592 
                 0.480689 
               
               
                 chrX 
                 18355897 
                 18356374 
                 4.07E−09 
                 brain 
                 −0.3703 
                 0.699427 
                 0.547643 
               
               
                 chr19 
                 44581428 
                 44584303 
                 4.17E−09 
                 brain 
                 1.129111 
                 0.159947 
                 0.374427 
               
               
                 chr1 
                 165182806 
                 165183330 
                 4.19E−09 
                 All 
                 0.078551 
                 1.160163 
                 0.736041 
               
               
                 chr17 
                 68094833 
                 68098785 
                 4.24E−09 
                 brain 
                 0.199103 
                 1.079328 
                 1.153802 
               
               
                 chr17 
                 4795197 
                 4796159 
                 4.26E−09 
                 liver 
                 1.18738 
                 0.182585 
                 1.068554 
               
               
                 chr19 
                 55744809 
                 55746038 
                 4.26E−09 
                 brain 
                 −0.03805 
                 0.758509 
                 1.008509 
               
               
                 chr6 
                 2712261 
                 2713113 
                 4.71E−09 
                 All 
                 −0.31861 
                 0.757329 
                 0.053413 
               
               
                 chr1 
                 207913994 
                 207914866 
                 4.78E−09 
                 All 
                 1.048671 
                 0.009665 
                 0.479916 
               
               
                 chr1 
                 228271526 
                 228273514 
                 4.85E−09 
                 All 
                 0.721839 
                 0.263038 
                 1.405718 
               
               
                 chr4 
                 3341125 
                 3342144 
                 4.90E−09 
                 brain 
                 0.237939 
                 1.277335 
                 1.144417 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 chr 
                 name 
                 annotation 
                 region 
                 island 
                 distToIsla 
               
               
                   
                   
               
               
                   
                 chr1 
                 PDE4DIP 
                 NM_022359 
                 overlaps 5′ 
                 cover 
                 0 
               
               
                   
                 chr1 
                 ERRFI1 
                 NM_018948 
                 upstream 
                 Shore 
                 0 
               
               
                   
                 chr10 
                 CPN1 
                 NM_001308 
                 overlaps 5′ 
                 Far 
                 15878 
               
               
                   
                 chr12 
                 GALNT9 
                 NM_021808 
                 upstream 
                 Shore 
                 603 
               
               
                   
                 chr12 
                 HOM-TES-103 
                 NM_001039670 
                 inside 
                 Shore 
                 1705 
               
               
                   
                 chr14 
                 THTPA 
                 NM_024328 
                 downstream 
                 Island 
                 0 
               
               
                   
                 chr14 
                 TRIM9 
                 NM_052978 
                 inside 
                 Island 
                 0 
               
               
                   
                 chr14 
                 RTN1 
                 NM_206852 
                 inside 
                 Shore 
                 251 
               
               
                   
                 chr15 
                 LRRN6A 
                 NM_032808 
                 inside 
                 Shore 
                 1495 
               
               
                   
                 chr15 
                 CHD2 
                 NM_001042572 
                 downstream 
                 Far 
                 9081 
               
               
                   
                 chr16 
                 GPT2 
                 NM_133443 
                 downstream 
                 Shore 
                 0 
               
               
                   
                 chr16 
                 GPT2 
                 NM_133443 
                 inside 
                 Shore 
                 1217 
               
               
                   
                 chr18 
                 ZNF532 
                 NM_018181 
                 inside 
                 Shore 
                 559 
               
               
                   
                 chr2 
                 SPTBN1 
                 NM_003128 
                 inside 
                 Shore 
                 660 
               
               
                   
                 chr20 
                 SS18L1 
                 NM_198935 
                 inside 
                 Far 
                 2587 
               
               
                   
                 chr4 
                 TSPAN5 
                 NM_005723 
                 inside 
                 Shore 
                 127 
               
               
                   
                 chr5 
                 RGMB 
                 NM_173670 
                 inside 
                 Shore 
                 781 
               
               
                   
                 chr8 
                 MTMR7 
                 NM_004686 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr8 
                 GDAP1 
                 NM_001040875 
                 inside 
                 Shore 
                 309 
               
               
                   
                 chrX 
                 SLITRK2 
                 NM_032539 
                 inside 
                 Shore 
                 1945 
               
               
                   
                 chrX 
                 TSPYL2 
                 NM_022117 
                 inside 
                 Far 
                 2034 
               
               
                   
                 chr17 
                 FLJ45079 
                 NM_001001685 
                 upstream 
                 Shore 
                 197 
               
               
                   
                 chr15 
                 MEIS2 
                 NM_172315 
                 inside 
                 Shore 
                 101 
               
               
                   
                 chr7 
                 MEST 
                 NM_177524 
                 inside 
                 Shore 
                 1026 
               
               
                   
                 chr1 
                 VANGL2 
                 NM_020335 
                 inside 
                 Shore 
                 372 
               
               
                   
                 chr11 
                 TIGD3 
                 NM_145719 
                 downstream 
                 Shore 
                 130 
               
               
                   
                 chr6 
                 KIAA1900 
                 NM_052904 
                 inside 
                 Shore 
                 487 
               
               
                   
                 chr20 
                 BMP2 
                 NM_001200 
                 downstream 
                 Far 
                 232877 
               
               
                   
                 chr17 
                 UBE2O 
                 NM_022066 
                 inside 
                 Shore 
                 541 
               
               
                   
                 chr17 
                 THRA 
                 NM_199334 
                 inside 
                 Shore 
                 360 
               
               
                   
                 chr7 
                 MKLN1 
                 NM_013255 
                 downstream 
                 Shore 
                 0 
               
               
                   
                 chr18 
                 TCF4 
                 NM_003199 
                 inside 
                 Far 
                 165726 
               
               
                   
                 chr14 
                 DDHD1 
                 NM_030637 
                 inside 
                 Shore 
                 393 
               
               
                   
                 chr19 
                 PSCD2 
                 NM_004228 
                 upstream 
                 Shore 
                 320 
               
               
                   
                 chr1 
                 ZNF238 
                 NM_006352 
                 inside 
                 Shore 
                 587 
               
               
                   
                 chr22 
                 C22orf26 
                 NM_018280 
                 upstream 
                 Shore 
                 635 
               
               
                   
                 chr22 
                 MN1 
                 NM_002430 
                 inside 
                 Shore 
                 738 
               
               
                   
                 chr12 
                 RPL6 
                 NM_000970 
                 downstream 
                 cover 
                 0 
               
               
                   
                 chr16 
                 XYLT1 
                 NM_022166 
                 inside 
                 Far 
                 869871 
               
               
                   
                 chr6 
                 LRRC1 
                 NM_018214 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr12 
                 VPS37B 
                 NM_024667 
                 inside 
                 Shore 
                 27 
               
               
                   
                 chr4 
                 CDKL2 
                 NM_003948 
                 upstream 
                 Shore 
                 0 
               
               
                   
                 chr10 
                 CUGBP2 
                 NM_001025077 
                 inside 
                 Far 
                 9377 
               
               
                   
                 chr19 
                 NFIX 
                 NM_002501 
                 inside 
                 Shore 
                 74 
               
               
                   
                 chr9 
                 OLFM1 
                 NM_006334 
                 inside 
                 Shore 
                 579 
               
               
                   
                 chr3 
                 DGKG 
                 NM_001346 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr13 
                 CCDC122 
                 NM_144974 
                 downstream 
                 Shore 
                 205 
               
               
                   
                 chr14 
                 THTPA 
                 NM_024328 
                 downstream 
                 Far 
                 5519 
               
               
                   
                 chr20 
                 PRNP 
                 NM_000311 
                 inside 
                 Shore 
                 263 
               
               
                   
                 chr18 
                 FLJ44881 
                 NM_207461 
                 downstream 
                 Shore 
                 295 
               
               
                   
                 chr7 
                 POR 
                 NM_000941 
                 inside 
                 Far 
                 3367 
               
               
                   
                 chr16 
                 SEPHS2 
                 NM_012248 
                 overlaps 3′ 
                 Shore 
                 55 
               
               
                   
                 chr1 
                 ACTN2 
                 NM_001103 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr1 
                 C1orf96 
                 NM_145257 
                 inside 
                 Shore 
                 1414 
               
               
                   
                 chr9 
                 PALM2 
                 NM_001037293 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr21 
                 ABCG1 
                 NM_207174 
                 inside 
                 Shore 
                 1439 
               
               
                   
                 chr21 
                 JAM2 
                 NM_021219 
                 inside 
                 Shore 
                 412 
               
               
                   
                 chr19 
                 ZNF160 
                 NM_033288 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chrX 
                 SYP 
                 NM_003179 
                 inside 
                 Shore 
                 1759 
               
               
                   
                 chr1 
                 TRIM62 
                 NM_018207 
                 inside 
                 Shore 
                 269 
               
               
                   
                 chr4 
                 KCNIP4 
                 NM_147182 
                 inside 
                 Shore 
                 32 
               
               
                   
                 chr17 
                 ABC1 
                 NM_022070 
                 inside 
                 Shore 
                 6 
               
               
                   
                 chr21 
                 COL18A1 
                 NM_030582 
                 inside 
                 cover 
                 0 
               
               
                   
                 chr2 
                 LONRF2 
                 NM_198461 
                 upstream 
                 Shore 
                 56 
               
               
                   
                 chr2 
                 YWHAQ 
                 NM_006826 
                 inside 
                 Shore 
                 1528 
               
               
                   
                 chr13 
                 PCDH9 
                 NM_020403 
                 inside 
                 Far 
                 2224 
               
               
                   
                 chr8 
                 MAL2 
                 NM_052886 
                 inside 
                 Shore 
                 4 
               
               
                   
                 chr17 
                 WIPI1 
                 NM_017983 
                 inside 
                 Shore 
                 558 
               
               
                   
                 chr5 
                 FBXL7 
                 NM_012304 
                 upstream 
                 Far 
                 2832 
               
               
                   
                 chr15 
                 NDNL2 
                 NM_138704 
                 overlaps 3′ 
                 Shore 
                 1133 
               
               
                   
                 chr8 
                 TNKS 
                 NM_003747 
                 upstream 
                 Shore 
                 1250 
               
               
                   
                 chr15 
                 MKRN3 
                 NM_005664 
                 overlaps 3′ 
                 Far 
                 120705 
               
               
                   
                 chr13 
                 TSC22D1 
                 NM_006022 
                 inside 
                 Far 
                 2361 
               
               
                   
                 chr20 
                 NKX2-2 
                 NM_002509 
                 upstream 
                 Far 
                 84879 
               
               
                   
                 chr6 
                 CGA 
                 NM_000735 
                 upstream 
                 Shore 
                 0 
               
               
                   
                 chr3 
                 SCHIP1 
                 NM_014575 
                 inside 
                 Far 
                 74473 
               
               
                   
                 chr16 
                 FOXC2 
                 NM_005251 
                 upstream 
                 Far 
                 2282 
               
               
                   
                 chr17 
                 HOXB7 
                 NM_004502 
                 overlaps 3′ 
                 Shore 
                 483 
               
               
                   
                 chr12 
                 TBX3 
                 NM_005996 
                 inside 
                 Far 
                 2380 
               
               
                   
                 chr22 
                 SERPIND1 
                 NM_000185 
                 inside 
                 Far 
                 74742 
               
               
                   
                 chr9 
                 ANP32B 
                 NM_006401 
                 downstream 
                 Shore 
                 561 
               
               
                   
                 chr10 
                 CNNM2 
                 NM_199077 
                 inside 
                 Shore 
                 117 
               
               
                   
                 chr6 
                 PAQR8 
                 NM_133367 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr8 
                 HEY1 
                 NM_012258 
                 overlaps 3′ 
                 Shore 
                 336 
               
               
                   
                 chr1 
                 TMEM58 
                 NM_198149 
                 inside 
                 Far 
                 60230 
               
               
                   
                 chr11 
                 DSCAML1 
                 NM_020693 
                 inside 
                 Shore 
                 979 
               
               
                   
                 chr10 
                 WAPAL 
                 NM_015045 
                 upstream 
                 Shore 
                 454 
               
               
                   
                 chr3 
                 SCHIP1 
                 NM_014575 
                 inside 
                 Shore 
                 729 
               
               
                   
                 chr10 
                 CXXC6 
                 NM_030625 
                 inside 
                 Shore 
                 1256 
               
               
                   
                 chr10 
                 PCBD1 
                 NM_000281 
                 inside 
                 Shore 
                 1319 
               
               
                   
                 chr5 
                 BASP1 
                 NM_006317 
                 inside 
                 Shore 
                 624 
               
               
                   
                 chr19 
                 ZNF615 
                 NM_198480 
                 inside 
                 Island 
                 0 
               
               
                   
                 chr7 
                 TBXAS1 
                 NM_030984 
                 downstream 
                 Shore 
                 963 
               
               
                   
                 chr11 
                 TMEM151 
                 NM_153266 
                 inside 
                 Shore 
                 284 
               
               
                   
                 chr12 
                 SLC2A13 
                 NM_052885 
                 inside 
                 Shore 
                 570 
               
               
                   
                 chr18 
                 C18orf51 
                 NM_001044369 
                 inside 
                 Far 
                 2280 
               
               
                   
                 chr12 
                 PHC1 
                 NM_004426 
                 inside 
                 Shore 
                 84 
               
               
                   
                 chr7 
                 HERPUD2 
                 NM_022373 
                 downstream 
                 Shore 
                 197 
               
               
                   
                 chr22 
                 FLJ27365 
                 NM_207477 
                 downstream 
                 Far 
                 3632 
               
               
                   
                 chr9 
                 bA16L21.2.1 
                 NM_001015882 
                 inside 
                 Shore 
                 241 
               
               
                   
                 chr3 
                 SOX2 
                 NM_003106 
                 upstream 
                 Shore 
                 865 
               
               
                   
                 chr5 
                 TMEM161B 
                 NM_153354 
                 upstream 
                 Shore 
                 321 
               
               
                   
                 chr22 
                 C22orf26 
                 NM_018280 
                 upstream 
                 Far 
                 2055 
               
               
                   
                 chr15 
                 MEIS2 
                 NM_172315 
                 inside 
                 Shore 
                 53 
               
               
                   
                 chr6 
                 PRRT1 
                 NM_030651 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr6 
                 KAAG1 
                 NM_181337 
                 upstream 
                 Shore 
                 55 
               
               
                   
                 chr11 
                 LRP5 
                 NM_002335 
                 inside 
                 Shore 
                 624 
               
               
                   
                 chr15 
                 DMXL2 
                 NM_015263 
                 inside 
                 Shore 
                 611 
               
               
                   
                 chr10 
                 KCNMA1 
                 NM_002247 
                 inside 
                 Shore 
                 985 
               
               
                   
                 chr12 
                 NT5DC3 
                 NM_001031701 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr1 
                 SCCPDH 
                 NM_016002 
                 inside 
                 Shore 
                 114 
               
               
                   
                 chr9 
                 ROR2 
                 NM_004560 
                 inside 
                 Shore 
                 1731 
               
               
                   
                 chr17 
                 RPL38 
                 NM_000999 
                 upstream 
                 Shore 
                 70 
               
               
                   
                 chr5 
                 IQGAP2 
                 NM_006633 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr14 
                 DPF3 
                 NM_012074 
                 inside 
                 Shore 
                 41 
               
               
                   
                 chr4 
                 PAPSS1 
                 NM_005443 
                 inside 
                 Shore 
                 136 
               
               
                   
                 chr19 
                 NFIX 
                 NM_002501 
                 downstream 
                 Far 
                 10181 
               
               
                   
                 chr3 
                 RAB6B 
                 NM_016577 
                 inside 
                 Shore 
                 654 
               
               
                   
                 chr12 
                 DYNLL1 
                 NM_001037495 
                 overlaps 5′ 
                 Shore 
                 312 
               
               
                   
                 chr3 
                 HRASLS 
                 NM_020386 
                 inside 
                 Shore 
                 206 
               
               
                   
                 chr18 
                 ZNF532 
                 NM_018181 
                 overlaps 3′ 
                 Shore 
                 0 
               
               
                   
                 chr10 
                 SH3PXD2A 
                 NM_014631 
                 inside 
                 Shore 
                 270 
               
               
                   
                 chr4 
                 DKFZP686A01247 
                 NM_014988 
                 inside 
                 Shore 
                 72 
               
               
                   
                 chr8 
                 HEY1 
                 NM_012258 
                 inside 
                 Island 
                 0 
               
               
                   
                 chr20 
                 FAM83C 
                 NM_178468 
                 overlaps 3′ 
                 Shore 
                 6 
               
               
                   
                 chr1 
                 PHGDH 
                 NM_006623 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr9 
                 TMEFF1 
                 NM_003692 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr19 
                 GNG7 
                 NM_052847 
                 inside 
                 Shore 
                 1165 
               
               
                   
                 chr11 
                 DPF2 
                 NM_006268 
                 inside 
                 Shore 
                 140 
               
               
                   
                 chr12 
                 SMARCD1 
                 NM_003076 
                 inside 
                 Shore 
                 1064 
               
               
                   
                 chr14 
                 BCL2L2 
                 NM_004050 
                 downstream 
                 Shore 
                 710 
               
               
                   
                 chr12 
                 CD63 
                 NM_001780 
                 inside 
                 Shore 
                 767 
               
               
                   
                 chr6 
                 B3GAT2 
                 NM_080742 
                 inside 
                 Shore 
                 251 
               
               
                   
                 chr2 
                 PSD4 
                 NM_012455 
                 downstream 
                 Shore 
                 158 
               
               
                   
                 chr1 
                 ATP8B2 
                 NM_001005855 
                 inside 
                 Shore 
                 195 
               
               
                   
                 chr19 
                 NFIX 
                 NM_002501 
                 inside 
                 Shore 
                 387 
               
               
                   
                 chr18 
                 ST8SIA3 
                 NM_015879 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr22 
                 MPPED1 
                 NM_001044370 
                 inside 
                 Shore 
                 753 
               
               
                   
                 chr8 
                 PPM2C 
                 NM_018444 
                 inside 
                 Shore 
                 43 
               
               
                   
                 chr1 
                 KCNJ9 
                 NM_004983 
                 inside 
                 Shore 
                 436 
               
               
                   
                 chr10 
                 8-Mar 
                 NM_001002266 
                 inside 
                 Far 
                 69029 
               
               
                   
                 chr4 
                 ALPK1 
                 NM_025144 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr8 
                 FZD3 
                 NM_017412 
                 downstream 
                 Shore 
                 495 
               
               
                   
                 chr6 
                 BAT2 
                 NM_004638 
                 inside 
                 Shore 
                 52 
               
               
                   
                 chr11 
                 HCCA2 
                 NM_053005 
                 inside 
                 Far 
                 2351 
               
               
                   
                 chr9 
                 MLLT3 
                 NM_004529 
                 inside 
                 Shore 
                 509 
               
               
                   
                 chr4 
                 C4orf30 
                 NM_017741 
                 downstream 
                 Shore 
                 0 
               
               
                   
                 chr7 
                 HOXA5 
                 NM_019102 
                 downstream 
                 Shore 
                 66 
               
               
                   
                 chr13 
                 TMTC4 
                 NM_032813 
                 upstream 
                 Far 
                 23274 
               
               
                   
                 chr17 
                 SOX9 
                 NM_000346 
                 inside 
                 Island 
                 0 
               
               
                   
                 chr8 
                 C8ORFK32 
                 NM_015912 
                 inside 
                 Shore 
                 258 
               
               
                   
                 chr6 
                 KCNK5 
                 NM_003740 
                 inside 
                 Shore 
                 640 
               
               
                   
                 chr1 
                 SDHC 
                 NM_001035512 
                 overlaps 3′ 
                 Island 
                 0 
               
               
                   
                 chr11 
                 PRDM10 
                 NM_020228 
                 inside 
                 Shore 
                 387 
               
               
                   
                 chr6 
                 HIST1H3E 
                 NM_003532 
                 overlaps 3′ 
                 Shore 
                 0 
               
               
                   
                 chr10 
                 ZNF438 
                 NM_182755 
                 upstream 
                 Shore 
                 35 
               
               
                   
                 chr7 
                 KIAA1706 
                 NM_030636 
                 downstream 
                 Shore 
                 0 
               
               
                   
                 chr12 
                 FBXO21 
                 NM_015002 
                 inside 
                 Shore 
                 404 
               
               
                   
                 chr12 
                 BCAT1 
                 NM_005504 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr19 
                 ZNF599 
                 NM_001007247 
                 inside 
                 Shore 
                 126 
               
               
                   
                 chr10 
                 HTRA1 
                 NM_002775 
                 inside 
                 Shore 
                 437 
               
               
                   
                 chr22 
                 C22orf5 
                 NM_012264 
                 promoter 
                 Shore 
                 72 
               
               
                   
                 chr5 
                 BTF3 
                 NM_001037637 
                 downstream 
                 Shore 
                 0 
               
               
                   
                 chr2 
                 MTA3 
                 NM_020744 
                 downstream 
                 Shore 
                 442 
               
               
                   
                 chr5 
                 FER 
                 NM_005246 
                 downstream 
                 Shore 
                 271 
               
               
                   
                 chr2 
                 MYCN 
                 NM_005378 
                 upstream 
                 cover 
                 0 
               
               
                   
                 chr10 
                 INA 
                 NM_032727 
                 inside 
                 Far 
                 3085 
               
               
                   
                 chr19 
                 NOVA2 
                 NM_002516 
                 upstream 
                 Far 
                 22266 
               
               
                   
                 chr4 
                 SYNPO2 
                 NM_133477 
                 inside 
                 Far 
                 52501 
               
               
                   
                 chr13 
                 LIG4 
                 NM_002312 
                 overlaps 5′ 
                 Shore 
                 0 
               
               
                   
                 chr1 
                 LOC148696 
                 NM_001039568 
                 downstream 
                 Far 
                 51665 
               
               
                   
                 chr8 
                 PPP2R2A 
                 NM_002717 
                 inside 
                 Shore 
                 1997 
               
               
                   
                 chr13 
                 MCF2L 
                 NM_024979 
                 inside 
                 Shore 
                 1119 
               
               
                   
                 chr2 
                 PCGF1 
                 NM_032673 
                 inside 
                 Shore 
                 1308 
               
               
                   
                 chr12 
                 CLSTN3 
                 NM_014718 
                 inside 
                 Far 
                 57129 
               
               
                   
                 chr1 
                 PSRC1 
                 NM_001005290 
                 inside 
                 Shore 
                 103 
               
               
                   
                 chr20 
                 GZF1 
                 NM_022482 
                 downstream 
                 Shore 
                 352 
               
               
                   
                 chr4 
                 CPE 
                 NM_001873 
                 inside 
                 Shore 
                 93 
               
               
                   
                 chr21 
                 WRB 
                 NM_004627 
                 inside 
                 Shore 
                 0 
               
               
                   
                 chr5 
                 C5orf33 
                 NM_153013 
                 promoter 
                 Shore 
                 0 
               
               
                   
                 chrX 
                 RIBC1 
                 NM_144968 
                 inside 
                 Shore 
                 265 
               
               
                   
                 chr2 
                 FLJ46838 
                 NM_001007546 
                 inside 
                 Shore 
                 243 
               
               
                   
                 chrX 
                 CDKL5 
                 NM_003159 
                 inside 
                 Shore 
                 1550 
               
               
                   
                 chr19 
                 IXL 
                 NM_017592 
                 overlaps 5′ 
                 Shore 
                 718 
               
               
                   
                 chr1 
                 C1orf32 
                 NM_199351 
                 inside 
                 Shore 
                 159 
               
               
                   
                 chr17 
                 SLC39A11 
                 NM_139177 
                 downstream 
                 Shore 
                 581 
               
               
                   
                 chr17 
                 ENO3 
                 NM_001976 
                 inside 
                 Shore 
                 545 
               
               
                   
                 chr19 
                 LOC554235 
                 NM_001024656 
                 upstream 
                 Shore 
                 875 
               
               
                   
                 chr6 
                 WRNIP1 
                 NM_020135 
                 inside 
                 Shore 
                 487 
               
               
                   
                 chr1 
                 G0S2 
                 NM_015714 
                 downstream 
                 Shore 
                 200 
               
               
                   
                 chr1 
                 GALNT2 
                 NM_004481 
                 inside 
                 Shore 
                 694 
               
               
                   
                 chr4 
                 RGS12 
                 NM_198227 
                 overlaps 3′ 
                 Far 
                 2387 
               
               
                   
                   
               
               
                   
                 FDR is false discovery rate. 
               
               
                   
                 Columns are chromosome, start, end, false discovery rate, tissue-specificity, brain M value, liver M value, spleen M value, gene, annotation, relation to gene, relation to CGI, distance to CGI 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Regions with cancer-specific differential methylation (C-DMRs) at a FDR of 5%. 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 relation 
                 Dist 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 to Dist 
                 To 
               
               
                 chr 
                 start 
                 end 
                 deltaM 
                 fdr 
                 state 
                 name 
                 annotation 
                 region 
                 to CGI 
                 CGI 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 chr10 
                 5774977 
                 5775480 
                 0.88404 
                 0 
                 Some methylation 
                 ASB13 
                 NM_024701 
                 upstream 
                 Far 
                 7274 
               
               
                 chr11 
                 117907224 
                 117907958 
                 1.00157 
                 0 
                 Some methylation 
                 TMEM25 
                 NM_032780 
                 inside 
                 Shore 
                 0 
               
               
                 chr11 
                 65947037 
                 65948698 
                 −0.88203 
                 0 
                 Less methylation 
                 NPAS4 
                 NM_178864 
                 inside 
                 Shore 
                 1064 
               
               
                 chr13 
                 113615559 
                 113616275 
                 −0.91383 
                 0 
                 Less methylation 
                 FAM70B 
                 NM_182614 
                 inside 
                 cover 
                 0 
               
               
                 chr15 
                 58474576 
                 58476390 
                 −0.80517 
                 0 
                 No methylation 
                 ANXA2 
                 NM_001002857 
                 inside 
                 Shore 
                 651 
               
               
                 chr19 
                 5159373 
                 5160095 
                 −1.01444 
                 0 
                 Less methylation 
                 PTPRS 
                 NM_130854 
                 inside 
                 Shore 
                 1469 
               
               
                 chr19 
                 5297115 
                 5297780 
                 −0.93292 
                 0 
                 No methylation 
                 PTPRS 
                 NM_130854 
                 upstream 
                 Far 
                 5054 
               
               
                 chr19 
                 55631525 
                 55632172 
                 −0.84621 
                 0 
                 Less methylation 
                 MYBPC2 
                 NM_004533 
                 inside 
                 Far 
                 4036 
               
               
                 chr19 
                 60702435 
                 60703541 
                 −0.93061 
                 0 
                 Less methylation 
                 NAT14 
                 NM_020378 
                 upstream 
                 Far 
                 3082 
               
               
                 chr20 
                 33650044 
                 33650445 
                 0.881805 
                 0 
                 More methylation 
                 SPAG4 
                 NM_003116 
                 downstream 
                 Shore 
                 1688 
               
               
                 chr21 
                 37858818 
                 37859555 
                 −1.16368 
                 0 
                 No methylation 
                 DYRK1A 
                 NM_001396 
                 upstream 
                 Shore 
                 402 
               
               
                 chr2 
                 147061940 
                 147063253 
                 −0.85834 
                 0 
                 Less methylation 
                 ACVR2A 
                 NM_001616 
                 downstream 
                 Shore 
                 91 
               
               
                 chr22 
                 35335058 
                 35336773 
                 −1.03729 
                 0 
                 Less methylation 
                 CACNG2 
                 NM_006078 
                 inside 
                 Far 
                 44058 
               
               
                 chr22 
                 48414225 
                 48414719 
                 −0.96407 
                 0 
                 Less methylation 
                 C22orf34 
                 NM_001039473 
                 inside 
                 Shore 
                 1806 
               
               
                 chr3 
                 193607217 
                 193607552 
                 −0.93573 
                 0 
                 Less methylation 
                 FGF12 
                 NM_021032 
                 inside 
                 Shore 
                 960 
               
               
                 chr3 
                 82629728 
                 82630444 
                 −0.83773 
                 0 
                 Less methylation 
                 GBE1 
                 NM_000158 
                 upstream 
                 Far 
                 309227 
               
               
                 chr4 
                 62618513 
                 62619190 
                 −0.87267 
                 0 
                 Less methylation 
                 LPHN3 
                 NM_015236 
                 inside 
                 Far 
                 552670 
               
               
                 chr5 
                 1718578 
                 1720081 
                 −1.00668 
                 0 
                 Less methylation 
                 MRPL36 
                 NM_032479 
                 downstream 
                 Shore 
                 106 
               
               
                 chr6 
                 52637426 
                 52638797 
                 −0.88756 
                 0 
                 No methylation 
                 TMEM14A 
                 NM_014051 
                 downstream 
                 Shore 
                 0 
               
               
                 chr7 
                 153219537 
                 153220325 
                 −1.02674 
                 0 
                 Less methylation 
                 DPP6 
                 NM_001039350 
                 inside 
                 Far 
                 2938 
               
               
                 chr7 
                 27106893 
                 27108170 
                 0.882121 
                 0 
                 More methylation 
                 HOXA2 
                 NM_006735 
                 inside 
                 Shore 
                 1536 
               
               
                 chr8 
                 819298 
                 820365 
                 −0.87447 
                 0 
                 Less methylation 
                 ERICH1 
                 NM_207332 
                 upstream 
                 Shore 
                 1879 
               
               
                 chr9 
                 94989150 
                 94990319 
                 0.845242 
                 0 
                 Some methylation 
                 WNK2 
                 NM_006648 
                 inside 
                 Shore 
                 1494 
               
               
                 chrX 
                 135941512 
                 135943110 
                 0.904877 
                 0 
                 Some methylation 
                 GPR101 
                 NM_054021 
                 promoter 
                 Island 
                 0 
               
               
                 chr13 
                 24843229 
                 24844191 
                 0.835162 
                 2.95E−12 
                 More methylation 
                 ATP8A2 
                 NM_016529 
                 downstream 
                 Shore 
                 0 
               
               
                 chr8 
                 144543158 
                 144544935 
                 −0.79612 
                 3.04E−12 
                 Less methylation 
                 RHPN1 
                 NM_052924 
                 upstream 
                 Far 
                 9061 
               
               
                 chr20 
                 15408602 
                 15408931 
                 −0.87712 
                 5.30E−12 
                 Less methylation 
                 C20orf133 
                 NM_001033087 
                 inside 
                 Far 
                 1092905 
               
               
                 chr19 
                 43436599 
                 43438474 
                 0.828947 
                 6.70E−12 
                 More methylation 
                 PPP1R14A 
                 NM_033256 
                 inside 
                 Shore 
                 4 
               
               
                 chr7 
                 27121979 
                 27122917 
                 0.793013 
                 1.34E−11 
                 Some methylation 
                 HOXA3 
                 NM_030661 
                 inside 
                 Shore 
                 28 
               
               
                 chr10 
                 129973472 
                 129974329 
                 −0.79104 
                 1.92E−11 
                 Less methylation 
                 MKI67 
                 NM_002417 
                 upstream 
                 Far 
                 19204 
               
               
                 chr7 
                 129912736 
                 129913242 
                 −0.82465 
                 2.24E−11 
                 Less methylation 
                 MEST 
                 NM_177524 
                 downstream 
                 Shore 
                 11 
               
               
                 chr15 
                 90735153 
                 90735977 
                 −0.78099 
                 4.62E−11 
                 Less methylation 
                 ST8SIA2 
                 NM_006011 
                 downstream 
                 Shore 
                 1704 
               
               
                 chr22 
                 36145002 
                 36145832 
                 0.778036 
                 5.64E−11 
                 Some methylation 
                 LRRC62 
                 NM_052906 
                 upstream 
                 Shore 
                 0 
               
               
                 chr5 
                 175019374 
                 175020506 
                 −0.77323 
                 7.72E−11 
                 Less methylation 
                 HRH2 
                 NM_022304 
                 downstream 
                 Shore 
                 1012 
               
               
                 chr8 
                 118032313 
                 118033443 
                 −0.76958 
                 8.22E−11 
                 Less methylation 
                 LOC441376 
                 NM_001025357 
                 upstream 
                 Far 
                 12173 
               
               
                 chr7 
                 27151643 
                 27153628 
                 0.72037 
                 8.57E−11 
                 More methylation 
                 HOXA6 
                 NM_024014 
                 inside 
                 Shore 
                 0 
               
               
                 chr12 
                 108883476 
                 108884015 
                 −0.79921 
                 8.98E−11 
                 Less methylation 
                 GIT2 
                 NM_139201 
                 inside 
                 Far 
                 34165 
               
               
                 chr7 
                 4865828 
                 4866751 
                 −0.75229 
                 1.80E−10 
                 Less methylation 
                 PAPOLB 
                 NM_020144 
                 inside 
                 Shore 
                 1111 
               
               
                 chr15 
                 70198422 
                 70199761 
                 −0.75665 
                 2.30E−10 
                 No methylation 
                 SENP8 
                 NM_145204 
                 inside 
                 Shore 
                 366 
               
               
                 chr19 
                 63146186 
                 63149953 
                 −0.69314 
                 2.31E−10 
                 Less methylation 
                 ZNF256 
                 NM_005773 
                 inside 
                 Shore 
                 545 
               
               
                 chr12 
                 128898887 
                 128900474 
                 −0.72032 
                 3.16E−10 
                 No methylation 
                 TMEM132D 
                 NM_133448 
                 inside 
                 Far 
                 5162 
               
               
                 chr1 
                 14092469 
                 14093393 
                 0.743518 
                 3.74E−10 
                 More methylation 
                 PRDM2 
                 NM_012231 
                 upstream 
                 Shore 
                 145 
               
               
                 chr20 
                 56858718 
                 56860946 
                 0.682357 
                 3.76E−10 
                 Some methylation 
                 GNAS 
                 NM_016592 
                 inside 
                 cover 
                 0 
               
               
                 chr6 
                 50873235 
                 50873811 
                 −0.77277 
                 3.81E−10 
                 Less methylation 
                 TFAP2B 
                 NM_003221 
                 downstream 
                 Far 
                 21434 
               
               
                 chr9 
                 101171244 
                 101172098 
                 −0.74221 
                 4.84E−10 
                 Less methylation 
                 SEC61B 
                 NM_006808 
                 upstream 
                 Far 
                 72210 
               
               
                 chr7 
                 145026589 
                 145027407 
                 −0.73801 
                 7.53E−10 
                 Less methylation 
                 CNTNAP2 
                 NM_014141 
                 downstream 
                 Far 
                 416556 
               
               
                 chr11 
                 73980533 
                 73981178 
                 −0.78485 
                 8.52E−10 
                 Less methylation 
                 POLD3 
                 NM_006591 
                 downstream 
                 Shore 
                 0 
               
               
                 chr5 
                 16236219 
                 16237106 
                 −0.72798 
                 1.00E−09 
                 No methylation 
                 FBXL7 
                 NM_012304 
                 upstream 
                 Far 
                 2799 
               
               
                 chr9 
                 137437549 
                 137438193 
                 −0.74586 
                 1.27E−09 
                 Less methylation 
                 KIAA0649 
                 NM_014811 
                 downstream 
                 Far 
                 6096 
               
               
                 chr8 
                 17060922 
                 17062917 
                 −0.68442 
                 1.34E−09 
                 Less methylation 
                 ZDHHC2 
                 NM_016353 
                 inside 
                 Shore 
                 1761 
               
               
                 chr9 
                 136758751 
                 136759638 
                 −0.72195 
                 1.46E−09 
                 Less methylation 
                 COL5A1 
                 NM_000093 
                 inside 
                 Far 
                 40696 
               
               
                 chr18 
                 73809395 
                 73809862 
                 −0.76199 
                 1.78E−09 
                 Less methylation 
                 GALR1 
                 NM_001480 
                 upstream 
                 Far 
                 9620 
               
               
                 chr3 
                 129687777 
                 129688211 
                 0.765371 
                 1.99E−09 
                 Some methylation 
                 GATA2 
                 NM_032638 
                 inside 
                 Shore 
                 0 
               
               
                 chr3 
                 191521264 
                 191521946 
                 −0.73631 
                 2.29E−09 
                 No methylation 
                 CLDN1 
                 NM_021101 
                 inside 
                 Shore 
                 562 
               
               
                 chr13 
                 42886712 
                 42887185 
                 −0.75536 
                 2.66E−09 
                 No methylation 
                 PIG38 
                 NM_017993 
                 inside 
                 Far 
                 370673 
               
               
                 chr7 
                 27147025 
                 27148414 
                 0.687423 
                 2.78E−09 
                 More methylation 
                 HOXA5 
                 NM_019102 
                 overlaps 3′ 
                 Shore 
                 724 
               
               
                 chr2 
                 4028054 
                 4028969 
                 −0.71686 
                 2.80E−09 
                 Less methylation 
                 ALLC 
                 NM_199232 
                 upstream 
                 cover 
                 0 
               
               
                 chr17 
                 74692697 
                 74693892 
                 −0.70553 
                 2.93E−09 
                 Less methylation 
                 LOC146713 
                 NM_001025448 
                 downstream 
                 Shore 
                 873 
               
               
                 chr12 
                 112557312 
                 112558104 
                 −0.75314 
                 3.06E−09 
                 Less methylation 
                 LHX5 
                 NM_022363 
                 upstream 
                 Far 
                 43177 
               
               
                 chr20 
                 44094989 
                 44097868 
                 −0.67672 
                 3.15E−09 
                 No methylation 
                 SLC12A5 
                 NM_020708 
                 inside 
                 Shore 
                 634 
               
               
                 chr7 
                 92075312 
                 92075873 
                 −0.7558 
                 3.60E−09 
                 Less methylation 
                 CDK6 
                 NM_001259 
                 inside 
                 Far 
                 17503 
               
               
                 chr7 
                 50103520 
                 50103993 
                 −0.74337 
                 5.51E−09 
                 Less methylation 
                 ZPBP 
                 NM_007009 
                 promoter 
                 Shore 
                 53 
               
               
                 chr2 
                 172826386 
                 172826961 
                 −0.72901 
                 5.75E−09 
                 No methylation 
                 DLX2 
                 NM_004405 
                 upstream 
                 Far 
                 18042 
               
               
                 chr8 
                 1032896 
                 1034248 
                 −0.68718 
                 5.85E−09 
                 Less methylation 
                 ERICH1 
                 NM_207332 
                 upstream 
                 Shore 
                 1718 
               
               
                 chr20 
                 56841054 
                 56842229 
                 −0.67616 
                 7.76E−09 
                 No methylation 
                 GNAS 
                 NM_016592 
                 downstream 
                 Far 
                 5761 
               
               
                 chr7 
                 27129188 
                 27131713 
                 0.62826 
                 7.80E−09 
                 More methylation 
                 HOXA3 
                 NM_153631 
                 inside 
                 cover 
                 0 
               
               
                 chr16 
                 86201868 
                 86205260 
                 −0.67852 
                 9.80E−09 
                 Less methylation 
                 JPH3 
                 NM_020655 
                 inside 
                 Shore 
                 327 
               
               
                 chr18 
                 32022373 
                 32023451 
                 −0.68242 
                 1.01E−08 
                 Less methylation 
                 MOCOS 
                 NM_017947 
                 inside 
                 Shore 
                 230 
               
               
                 chr16 
                 31139986 
                 31140921 
                 −0.70124 
                 1.03E−08 
                 Less methylation 
                 TRIM72 
                 NM_001008274 
                 inside 
                 Far 
                 2105 
               
               
                 chrX 
                 23042002 
                 23042577 
                 −0.73787 
                 1.05E−08 
                 Less methylation 
                 DDX53 
                 NM_182699 
                 upstream 
                 Far 
                 217628 
               
               
                 chr12 
                 16648817 
                 16649638 
                 0.693703 
                 1.13E−08 
                 Some methylation 
                 LMO3 
                 NM_018640 
                 inside 
                 Far 
                 693016 
               
               
                 chr11 
                 2190993 
                 2192468 
                 −0.65402 
                 1.36E−08 
                 Less methylation 
                 TH 
                 NM_000360 
                 upstream 
                 Far 
                 46172 
               
               
                 chr6 
                 168586102 
                 168588777 
                 0.621865 
                 1.36E−08 
                 More methylation 
                 SMOC2 
                 NM_022138 
                 inside 
                 Shore 
                 153 
               
               
                 chr4 
                 172202321 
                 172202941 
                 −0.71014 
                 1.39E−08 
                 Less methylation 
                 GALNT17 
                 NM_001034845 
                 downstream 
                 Far 
                 767368 
               
               
                 chr20 
                 3603786 
                 3604568 
                 −0.69261 
                 1.43E−08 
                 No methylation 
                 ADAM33 
                 NM_025220 
                 inside 
                 Shore 
                 1013 
               
               
                 chr7 
                 1182527 
                 1183550 
                 −0.70109 
                 1.53E−08 
                 Less methylation 
                 ZFAND2A 
                 NM_182491 
                 upstream 
                 Far 
                 15857 
               
               
                 chr2 
                 242632926 
                 242634574 
                 −0.69924 
                 2.62E−08 
                 Less methylation 
                 FLJ33590 
                 NM_173821 
                 upstream 
                 Shore 
                 1740 
               
               
                 chr14 
                 95577239 
                 95578925 
                 −0.64697 
                 3.05E−08 
                 No methylation 
                 C14orf132 
                 NM_020215 
                 inside 
                 Shore 
                 1084 
               
               
                 chr8 
                 966339 
                 968282 
                 −0.62553 
                 3.25E−08 
                 Less methylation 
                 ERICH1 
                 NM_207332 
                 upstream 
                 Shore 
                 581 
               
               
                 chrX 
                 142544143 
                 142544508 
                 −0.72871 
                 3.62E−08 
                 Less methylation 
                 SLITRK4 
                 NM_173078 
                 inside 
                 Far 
                 4568 
               
               
                 chr7 
                 50436454 
                 50438081 
                 −0.63782 
                 3.80E−08 
                 Less methylation 
                 IKZF1 
                 NM_006060 
                 overlaps 5′ 
                 Shore 
                 560 
               
               
                 chr13 
                 87123702 
                 87125149 
                 0.64054 
                 3.98E−08 
                 Some methylation 
                 SLITRK5 
                 NM_015567 
                 inside 
                 cover 
                 0 
               
               
                 chr12 
                 88272781 
                 88274261 
                 −0.65038 
                 4.42E−08 
                 Less methylation 
                 DUSP6 
                 NM_001946 
                 upstream 
                 Shore 
                 506 
               
               
                 chr13 
                 112142200 
                 112143003 
                 −0.6783 
                 4.68E−08 
                 Less methylation 
                 C13orf28 
                 NM_145248 
                 upstream 
                 Far 
                 11335 
               
               
                 chr7 
                 80386676 
                 80389252 
                 −0.60191 
                 4.84E−08 
                 No methylation 
                 SEMA3C 
                 NM_006379 
                 promoter 
                 Shore 
                 14 
               
               
                 chr7 
                 90064351 
                 90065062 
                 0.677011 
                 5.06E−08 
                 Some methylation 
                 PFTK1 
                 NM_012395 
                 downstream 
                 Shore 
                 51 
               
               
                 chr8 
                 100031456 
                 100033208 
                 0.618925 
                 5.12E−08 
                 Some methylation 
                 OSR2 
                 NM_053001 
                 inside 
                 Shore 
                 842 
               
               
                 chr13 
                 110126686 
                 110127336 
                 0.682652 
                 5.44E−08 
                 More methylation 
                 FLJ12118 
                 NM_024537 
                 inside 
                 Shore 
                 1831 
               
               
                 chr8 
                 846979 
                 849372 
                 −0.59665 
                 5.47E−08 
                 Less methylation 
                 ERICH1 
                 NM_207332 
                 upstream 
                 Far 
                 6574 
               
               
                 chr11 
                 103540808 
                 103541706 
                 −0.6721 
                 5.56E−08 
                 Less methylation 
                 PDGFD 
                 NM_025208 
                 upstream 
                 Shore 
                 540 
               
               
                 chr3 
                 28591265 
                 28591843 
                 0.687621 
                 6.39E−08 
                 Some methylation 
                 ZCWPW2 
                 NM_001040432 
                 upstream 
                 Shore 
                 0 
               
               
                 chr8 
                 98356982 
                 98358151 
                 −0.64161 
                 6.46E−08 
                 Less methylation 
                 TSPYL5 
                 NM_033512 
                 inside 
                 Shore 
                 629 
               
               
                 chr5 
                 3586182 
                 3587073 
                 −0.70608 
                 6.57E−08 
                 Less methylation 
                 IRX1 
                 NM_024337 
                 downstream 
                 Shore 
                 1557 
               
               
                 chr20 
                 4928754 
                 4929383 
                 0.695671 
                 6.64E−08 
                 Some methylation 
                 SLC23A2 
                 NM_005116 
                 inside 
                 Far 
                 111977 
               
               
                 chr12 
                 128900526 
                 128905070 
                 −0.5668 
                 8.89E−08 
                 Less methylation 
                 TMEM132D 
                 NM_133448 
                 inside 
                 Shore 
                 566 
               
               
                 chr5 
                 7900127 
                 7901201 
                 −0.65677 
                 9.34E−08 
                 Less methylation 
                 FASTKD3 
                 NM_024091 
                 downstream 
                 Shore 
                 1744 
               
               
                 chr19 
                 35406489 
                 35408138 
                 0.619251 
                 9.87E−08 
                 Some methylation 
                 ZNF536 
                 NM_014717 
                 downstream 
                 cover 
                 0 
               
               
                 chr7 
                 3984090 
                 3985861 
                 −0.6193 
                 9.87E−08 
                 Less methylation 
                 SDK1 
                 NM_152744 
                 inside 
                 Far 
                 134310 
               
               
                 chr18 
                 75366596 
                 75367142 
                 −0.77008 
                 1.07E−07 
                 Less methylation 
                 NFATC1 
                 NM_172389 
                 inside 
                 Far 
                 4639 
               
               
                 chr5 
                 11954677 
                 11955633 
                 −0.64541 
                 1.12E−07 
                 Less methylation 
                 CTNND2 
                 NM_001332 
                 inside 
                 Shore 
                 917 
               
               
                 chr11 
                 2243719 
                 2244678 
                 −0.64164 
                 1.20E−07 
                 Less methylation 
                 ASCL2 
                 NM_005170 
                 downstream 
                 Far 
                 2002 
               
               
                 chr9 
                 137111474 
                 137112189 
                 −0.65985 
                 1.32E−07 
                 Less methylation 
                 OLFM1 
                 NM_006334 
                 inside 
                 Far 
                 3926 
               
               
                 chr7 
                 32076356 
                 32076691 
                 0.709313 
                 1.58E−07 
                 Some methylation 
                 PDE1C 
                 NM_005020 
                 inside 
                 Shore 
                 0 
               
               
                 chr11 
                 19323912 
                 19324554 
                 0.68291 
                 1.77E−07 
                 Some methylation 
                 E2F8 
                 NM_024680 
                 upstream 
                 inside 
                 0 
               
               
                 chr20 
                 59905352 
                 59906092 
                 −0.67681 
                 1.89E−07 
                 Less methylation 
                 CDH4 
                 NM_001794 
                 inside 
                 Shore 
                 1622 
               
               
                 chr11 
                 134186796 
                 134187368 
                 −0.6669 
                 2.01E−07 
                 Less methylation 
                 B3GAT1 
                 NM_018644 
                 upstream 
                 Far 
                 48599 
               
               
                 chr7 
                 142264591 
                 142265022 
                 −0.68427 
                 2.20E−07 
                 Less methylation 
                 EPHB6 
                 NM_004445 
                 inside 
                 Shore 
                 1283 
               
               
                 chr6 
                 10501357 
                 10502013 
                 0.657096 
                 2.24E−07 
                 Some methylation 
                 TFAP2A 
                 NM_001032280 
                 downstream 
                 Far 
                 2273 
               
               
                 chr7 
                 42233455 
                 42234204 
                 0.645604 
                 2.40E−07 
                 More methylation 
                 GLI3 
                 NM_000168 
                 upstream 
                 Shore 
                 0 
               
               
                 chr12 
                 38783074 
                 38784521 
                 0.600023 
                 2.59E−07 
                 More methylation 
                 SLC2A13 
                 NM_052885 
                 inside 
                 Shore 
                 708 
               
               
                 chr8 
                 117611158 
                 117611838 
                 −0.64748 
                 3.10E−07 
                 Less methylation 
                 EIF3S3 
                 NM_003756 
                 downstream 
                 Far 
                 225273 
               
               
                 chr11 
                 31966319 
                 31967492 
                 −0.63749 
                 3.15E−07 
                 No methylation 
                 RCN1 
                 NM_002901 
                 downstream 
                 Shore 
                 699 
               
               
                 chr17 
                 14831980 
                 14832519 
                 −0.66274 
                 3.17E−07 
                 Less methylation 
                 FLJ45831 
                 NM_001001684 
                 upstream 
                 Far 
                 272136 
               
               
                 chr21 
                 42057731 
                 42059424 
                 −0.58952 
                 3.54E−07 
                 Less methylation 
                 RIPK4 
                 NM_020639 
                 inside 
                 Shore 
                 0 
               
               
                 chr11 
                 133791126 
                 133793856 
                 −0.56461 
                 3.77E−07 
                 No methylation 
                 B3GAT1 
                 NM_018644 
                 upstream 
                 Far 
                 2997 
               
               
                 chr8 
                 22469866 
                 22470840 
                 −0.62573 
                 3.77E−07 
                 Less methylation 
                 SORBS3 
                 NM_005775 
                 inside 
                 Far 
                 4286 
               
               
                 chr3 
                 129686645 
                 129687266 
                 0.658959 
                 3.87E−07 
                 More methylation 
                 GATA2 
                 NM_032638 
                 inside 
                 Shore 
                 916 
               
               
                 chr1 
                 221053963 
                 221054618 
                 −0.65816 
                 4.06E−07 
                 Less methylation 
                 FLJ43505 
                 NM_207468 
                 upstream 
                 Shore 
                 249 
               
               
                 chr10 
                 3499370 
                 3500060 
                 −0.64479 
                 4.34E−07 
                 No methylation 
                 PITRM1 
                 NM_014889 
                 upstream 
                 Far 
                 8794 
               
               
                 chr20 
                 48778557 
                 48780262 
                 −0.59546 
                 4.34E−07 
                 No methylation 
                 PARD6B 
                 NM_032521 
                 downstream 
                 Shore 
                 510 
               
               
                 chr7 
                 152249022 
                 152250754 
                 −0.63648 
                 4.67E−07 
                 Less methylation 
                 ACTR3B 
                 NM_020445 
                 upstream 
                 Far 
                 2095 
               
               
                 chr12 
                 130718351 
                 130718755 
                 −0.68171 
                 4.82E−07 
                 Less methylation 
                 SFRS8 
                 NM_004592 
                 downstream 
                 Far 
                 5588 
               
               
                 chr14 
                 57669356 
                 57669927 
                 −0.65813 
                 5.16E−07 
                 Less methylation 
                 C14orf37 
                 NM_001001872 
                 inside 
                 Far 
                 18117 
               
               
                 chr10 
                 101273308 
                 101274941 
                 0.602562 
                 5.43E−07 
                 Some methylation 
                 NKX2-3 
                 NM_145285 
                 downstream 
                 Shore 
                 378 
               
               
                 chr18 
                 491107 
                 491721 
                 0.648047 
                 5.52E−07 
                 More methylation 
                 COLEC12 
                 NM_130386 
                 upstream 
                 Shore 
                 385 
               
               
                 chr16 
                 25608094 
                 25609031 
                 −0.61772 
                 5.78E−07 
                 No methylation 
                 HS3ST4 
                 NM_006040 
                 downstream 
                 Shore 
                 1425 
               
               
                 chr19 
                 50669649 
                 50670313 
                 0.642613 
                 5.96E−07 
                 More methylation 
                 FOSB 
                 NM_006732 
                 overlaps 5′ 
                 Shore 
                 1547 
               
               
                 chr11 
                 132451977 
                 132454794 
                 −0.55094 
                 6.61E−07 
                 Less methylation 
                 OPCML 
                 NM_001012393 
                 inside 
                 Far 
                 2108 
               
               
                 chr13 
                 100427918 
                 100428562 
                 −0.64421 
                 6.75E−07 
                 Less methylation 
                 VGCNL1 
                 NM_052867 
                 downstream 
                 Far 
                 302194 
               
               
                 chr19 
                 4505154 
                 4505870 
                 −0.62946 
                 6.75E−07 
                 Less methylation 
                 SEMA6B 
                 NM_020241 
                 inside 
                 Shore 
                 1066 
               
               
                 chr7 
                 139121471 
                 139122220 
                 0.626218 
                 6.75E−07 
                 More methylation 
                 TBXAS1 
                 NM_030984 
                 downstream 
                 Shore 
                 1655 
               
               
                 chr10 
                 1437553 
                 1439093 
                 −0.59022 
                 6.89E−07 
                 Less methylation 
                 ADARB2 
                 NM_018702 
                 inside 
                 Far 
                 7539 
               
               
                 chr13 
                 67580738 
                 67581346 
                 −0.63959 
                 6.96E−07 
                 Less methylation 
                 PCDH9 
                 NM_020403 
                 upstream 
                 Far 
                 875559 
               
               
                 chr3 
                 174341049 
                 174341309 
                 −0.70742 
                 7.33E−07 
                 Less methylation 
                 SPATA16 
                 NM_031955 
                 inside 
                 Far 
                 254652 
               
               
                 chr15 
                 67494729 
                 67495415 
                 −0.63108 
                 7.40E−07 
                 No methylation 
                 KIF23 
                 NM_004856 
                 inside 
                 Shore 
                 323 
               
               
                 chr12 
                 52430235 
                 52431287 
                 0.615375 
                 7.52E−07 
                 Some methylation 
                 CALCOCO1 
                 NM_020898 
                 upstream 
                 Island 
                 0 
               
               
                 chr1 
                 32992444 
                 32992959 
                 0.649479 
                 8.12E−07 
                 Some methylation 
                 KIAA1522 
                 NM_020888 
                 inside 
                 Shore 
                 0 
               
               
                 chr14 
                 52326048 
                 52327349 
                 −0.60366 
                 8.12E−07 
                 No methylation 
                 GNPNAT1 
                 NM_198066 
                 inside 
                 Shore 
                 65 
               
               
                 chr6 
                 80711271 
                 80712497 
                 −0.59439 
                 8.33E−07 
                 Less methylation 
                 ELOVL4 
                 NM_022726 
                 inside 
                 Shore 
                 966 
               
               
                 chr5 
                 132392 
                 134486 
                 −0.57195 
                 8.95E−07 
                 Less methylation 
                 KIAA1909 
                 NM_052909 
                 downstream 
                 Shore 
                 1942 
               
               
                 chr3 
                 148446946 
                 148448043 
                 −0.61085 
                 9.51E−07 
                 Less methylation 
                 ZIC4 
                 NM_032153 
                 downstream 
                 Far 
                 111759 
               
               
                 chr13 
                 113548234 
                 113549273 
                 0.600339 
                 9.66E−07 
                 More methylation 
                 GAS6 
                 NM_000820 
                 inside 
                 Shore 
                 99 
               
               
                 chr11 
                 133445488 
                 133446499 
                 −0.61556 
                 1.00E−06 
                 Less methylation 
                 JAM3 
                 NM_032801 
                 inside 
                 Shore 
                 597 
               
               
                 chr22 
                 47455137 
                 47456387 
                 −0.58401 
                 1.05E−06 
                 Less methylation 
                 FAM19A5 
                 NM_015381 
                 inside 
                 Far 
                 4801 
               
               
                 chr8 
                 132984463 
                 132985363 
                 −0.6234 
                 1.10E−06 
                 Less methylation 
                 KIAA0143 
                 NM_015137 
                 downstream 
                 Shore 
                 141 
               
               
                 chr2 
                 100303400 
                 100304122 
                 0.61944 
                 1.14E−06 
                 More methylation 
                 LONRF2 
                 NM_198461 
                 upstream 
                 Shore 
                 89 
               
               
                 chr17 
                 22902924 
                 22903499 
                 −0.63407 
                 1.14E−06 
                 Less methylation 
                 KSR1 
                 NM_014238 
                 inside 
                 Far 
                 53125 
               
               
                 chr1 
                 206062462 
                 206063842 
                 0.573914 
                 1.22E−06 
                 Some methylation 
                 LOC148696 
                 NM_001039568 
                 overlaps 5′ 
                 Far 
                 44643 
               
               
                 chr5 
                 134553843 
                 134554653 
                 0.610755 
                 1.28E−06 
                 More methylation 
                 H2AFY 
                 NM_138609 
                 downstream 
                 Shore 
                 173 
               
               
                 chr22 
                 46984389 
                 46985561 
                 −0.58562 
                 1.31E−06 
                 Less methylation 
                 LOC388915 
                 NM_001010902 
                 upstream 
                 Shore 
                 218 
               
               
                 chr19 
                 40896785 
                 40897432 
                 0.623253 
                 1.34E−06 
                 More methylation 
                 ZBTB32 
                 NM_014383 
                 inside 
                 Shore 
                 1492 
               
               
                 chr7 
                 149667145 
                 149668311 
                 0.582745 
                 1.37E−06 
                 More methylation 
                 RARRES2 
                 NM_002889 
                 inside 
                 Shore 
                 81 
               
               
                 chr4 
                 81341228 
                 81342411 
                 0.593058 
                 1.40E−06 
                 More methylation 
                 PRDM8 
                 NM_020226 
                 inside 
                 Shore 
                 121 
               
               
                 chr12 
                 4889976 
                 4890592 
                 0.629828 
                 1.42E−06 
                 Some methylation 
                 KCNA1 
                 NM_000217 
                 downstream 
                 inside 
                 0 
               
               
                 chr19 
                 36535109 
                 36535822 
                 0.615047 
                 1.43E−06 
                 More methylation 
                 TSHZ3 
                 NM_020856 
                 upstream 
                 Shore 
                 0 
               
               
                 chr10 
                 24025406 
                 24026498 
                 −0.60568 
                 1.43E−06 
                 No methylation 
                 C10orf67 
                 NM_153714 
                 upstream 
                 Shore 
                 422 
               
               
                 chr19 
                 38866174 
                 38866577 
                 −0.67497 
                 1.47E−06 
                 Less methylation 
                 CHST8 
                 NM_022467 
                 downstream 
                 Shore 
                 607 
               
               
                 chr19 
                 16876414 
                 16876750 
                 −0.6835 
                 1.49E−06 
                 Less methylation 
                 CPAMD8 
                 NM_015692 
                 inside 
                 Far 
                 6557 
               
               
                 chr11 
                 31780765 
                 31782078 
                 0.584509 
                 1.55E−06 
                 Some methylation 
                 PAX6 
                 NM_000280 
                 inside 
                 Shore 
                 241 
               
               
                 chr11 
                 45645190 
                 45645996 
                 −0.6053 
                 1.70E−06 
                 Less methylation 
                 CHST1 
                 NM_003654 
                 upstream 
                 Shore 
                 1119 
               
               
                 chr13 
                 21140646 
                 21141497 
                 0.598118 
                 1.82E−06 
                 Some methylation 
                 FGF9 
                 NM_002010 
                 downstream 
                 Shore 
                 0 
               
               
                 chr8 
                 53636369 
                 53637193 
                 −0.60042 
                 1.87E−06 
                 Less methylation 
                 UNQ9433 
                 NM_207413 
                 inside 
                 Far 
                 2904 
               
               
                 chr10 
                 102097628 
                 102098179 
                 −0.64186 
                 2.02E−06 
                 No methylation 
                 SCD 
                 NM_005063 
                 inside 
                 Shore 
                 0 
               
               
                 chr13 
                 109229161 
                 109231936 
                 −0.52866 
                 2.19E−06 
                 Less methylation 
                 IRS2 
                 NM_003749 
                 inside 
                 Shore 
                 531 
               
               
                 chr15 
                 53707187 
                 53707654 
                 −0.63505 
                 2.19E−06 
                 Less methylation 
                 PRTG 
                 NM_173814 
                 inside 
                 Far 
                 38667 
               
               
                 chr11 
                 1861758 
                 1862726 
                 −0.58891 
                 2.22E−06 
                 Less methylation 
                 LSP1 
                 NM_001013255 
                 inside 
                 Shore 
                 1848 
               
               
                 chr20 
                 24399098 
                 24400197 
                 0.576246 
                 2.35E−06 
                 Some methylation 
                 C20orf39 
                 NM_024893 
                 inside 
                 Island 
                 0 
               
               
                 chr13 
                 113850874 
                 113851696 
                 0.595891 
                 2.36E−06 
                 More methylation 
                 RASA3 
                 NM_007368 
                 inside 
                 Far 
                 2472 
               
               
                 chr6 
                 7413675 
                 7414250 
                 −0.61922 
                 2.43E−06 
                 Less methylation 
                 RIOK1 
                 NM_153005 
                 upstream 
                 Far 
                 72267 
               
               
                 chr10 
                 124898365 
                 124898865 
                 0.631343 
                 2.63E−06 
                 Some methylation 
                 HMX2 
                 NM_005519 
                 inside 
                 inside 
                 0 
               
               
                 chr7 
                 5360462 
                 5361424 
                 0.593453 
                 2.65E−06 
                 More methylation 
                 SLC29A4 
                 NM_153247 
                 upstream 
                 Shore 
                 974 
               
               
                 chr14 
                 100996473 
                 100997806 
                 −0.5653 
                 2.71E−06 
                 Less methylation 
                 DIO3 
                 NM_001362 
                 downstream 
                 Shore 
                 725 
               
               
                 chr19 
                 13473726 
                 13475470 
                 −0.56537 
                 2.71E−06 
                 Less methylation 
                 CACNA1A 
                 NM_023035 
                 inside 
                 Far 
                 2282 
               
               
                 chr8 
                 3257254 
                 3257862 
                 −0.61199 
                 2.86E−06 
                 Less methylation 
                 CSMD1 
                 NM_033225 
                 inside 
                 Far 
                 389899 
               
               
                 chr16 
                 49141667 
                 49142498 
                 −0.59792 
                 2.87E−06 
                 Less methylation 
                 NKD1 
                 NM_033119 
                 inside 
                 Shore 
                 701 
               
               
                 chr5 
                 158465126 
                 158466712 
                 0.548688 
                 2.93E−06 
                 Some methylation 
                 EBF1 
                 NM_024007 
                 upstream 
                 cover 
                 0 
               
               
                 chr19 
                 3240846 
                 3241491 
                 −0.60751 
                 2.96E−06 
                 Less methylation 
                 BRUNOL5 
                 NM_021938 
                 inside 
                 Far 
                 2776 
               
               
                 chr6 
                 5946646 
                 5947326 
                 0.603987 
                 2.96E−06 
                 Some methylation 
                 NRN1 
                 NM_016588 
                 inside 
                 Shore 
                 144 
               
               
                 chr7 
                 154079253 
                 154079678 
                 −0.65898 
                 3.29E−06 
                 Less methylation 
                 DPP6 
                 NM_001936 
                 inside 
                 Far 
                 93314 
               
               
                 chr8 
                 144372893 
                 144373912 
                 −0.59142 
                 3.41E−06 
                 No methylation 
                 LOC338328 
                 NM_178172 
                 upstream 
                 Far 
                 9171 
               
               
                 chr16 
                 4101996 
                 4102769 
                 0.594061 
                 3.47E−06 
                 Some methylation 
                 ADCY9 
                 NM_001116 
                 inside 
                 Far 
                 2040 
               
               
                 chr20 
                 61186086 
                 61186916 
                 −0.58801 
                 3.49E−06 
                 Less methylation 
                 BHLHB4 
                 NM_080606 
                 upstream 
                 Shore 
                 1296 
               
               
                 chr1 
                 203580235 
                 203580810 
                 0.611495 
                 3.58E−06 
                 More methylation 
                 KLHDC8A 
                 NM_018203 
                 inside 
                 Shore 
                 36 
               
               
                 chr2 
                 128944074 
                 128944714 
                 −0.61563 
                 3.59E−06 
                 Less methylation 
                 HS6ST1 
                 NM_004807 
                 upstream 
                 Shore 
                 357 
               
               
                 chr20 
                 48848947 
                 48849522 
                 0.611074 
                 3.65E−06 
                 More methylation 
                 BCAS4 
                 NM_017843 
                 inside 
                 Far 
                 3398 
               
               
                 chr18 
                 75183050 
                 75183445 
                 0.635066 
                 3.79E−06 
                 More methylation 
                 ATP9B 
                 NM_198531 
                 inside 
                 Far 
                 5006 
               
               
                 chr6 
                 133602937 
                 133603652 
                 0.618352 
                 3.94E−06 
                 More methylation 
                 EYA4 
                 NM_172103 
                 downstream 
                 Shore 
                 127 
               
               
                 chr9 
                 97304533 
                 97306736 
                 0.542219 
                 4.02E−06 
                 More methylation 
                 PTCH1 
                 NM_000264 
                 inside 
                 Shore 
                 1560 
               
               
                   
               
               
                 DeltaM is cancer minus normal. 
               
               
                 FDR is false discovery rate. 
               
               
                 State: “Some methylation” means some methylation in tumor, none in normal; “Less methylation” means less in tumor than normal. “More methylation” means more in tumor than normal; “No methylation” means none in tumor, some in normal. 
               
               
                 Columns are chromosome, start, end, delta M, fdr, overall methylation state, gene, annotation, relation to gene, relation to CGI, distance to CGI 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 Relationship between tissue methylation-specific gene expression and experimental demethylation 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Mean 
                   
                 AZA/ 
                   
                   
                   
                 TISSUES 
               
               
                 Gene 
                 expression 
                 mean 
                 HCT1 16 
                 AZA_expression_direc- 
                 AZA 
                 TISSUES_Diff_expression 
                 expression 
               
               
                 Description 
                 (AZA) 
                 HCT116 
                 (mean) 
                 tion 
                 P-value 
                 (L − B) 
                 P-value 
               
               
                   
               
               
                 MEF2C 
                 1.50 
                 0.94 
                 1.60 
                 increase 
                 0.0167 
                 −5.4 
                 1.10E−05 
               
               
                 CCK 
                 1.68 
                 0.96 
                 1.74 
                 increase 
                 0.0256 
                 −5.2 
                 4.50E−05 
               
               
                 NTRK2 
                 2.11 
                 0.95 
                 2.23 
                 increase 
                 0.0167 
                 −4.7 
                 4.40E−05 
               
               
                 SNCA 
                 0.86 
                 0.52 
                 1.67 
                 increase 
                 0.0256 
                 −4.3 
                 6.30E−05 
               
               
                 HSPA8 
                 5.33 
                 2.89 
                 1.85 
                 increase 
                 0.0167 
                 −3.3 
                 0.00053 
               
               
                 WRB 
                 0.88 
                 0.56 
                 1.57 
                 increase 
                 0.0256 
                 −2.2 
                 0.00037 
               
               
                 PIN 
                 1.17 
                 0.67 
                 1.75 
                 increase 
                 0.0167 
                 −1.8 
                 6.90E−05 
               
               
                 SOX9 
                 2.78 
                 1.81 
                 1.53 
                 increase 
                 0.0167 
                 −1.6 
                 0.0042 
               
               
                 KAL1 
                 1.79 
                 1.04 
                 1.73 
                 increase 
                 0.0256 
                 −1.5 
                 0.00058 
               
               
                 FYN 
                 0.91 
                 0.58 
                 1.57 
                 increase 
                 0.0167 
                 −1.5 
                 0.0071 
               
               
                 ABCC5 
                 1.49 
                 0.90 
                 1.65 
                 increase 
                 0.0256 
                 −1.5 
                 4.20E−05 
               
               
                 MTMR6 
                 1.72 
                 1.11 
                 1.55 
                 increase 
                 0.0476 
                 −1 
                 0.0039 
               
               
                 SHC1 
                 1.99 
                 1.17 
                 1.70 
                 increase 
                 0.0167 
                 1 
                 8.00E−04 
               
               
                 S100A10 
                 1.27 
                 0.84 
                 1.51 
                 increase 
                 0.0167 
                 1.1 
                 0.0014 
               
               
                 IFITM3 
                 2.65 
                 1.26 
                 2.11 
                 increase 
                 0.0256 
                 1.2 
                 0.056 
               
               
                 IFITM3 
                 3.12 
                 1.05 
                 2.97 
                 increase 
                 0.0167 
                 1.2 
                 0.056 
               
               
                 DUSP6 
                 6.10 
                 3.29 
                 1.85 
                 increase 
                 0.0167 
                 1.3 
                 0.004 
               
               
                 ACADVL 
                 1.71 
                 1.12 
                 1.53 
                 increase 
                 0.0167 
                 1.3 
                 0.012 
               
               
                 MT2A 
                 3.31 
                 2.20 
                 1.50 
                 increase 
                 0.0256 
                 1.6 
                 0.044 
               
               
                 KCNJ8 
                 2.57 
                 1.23 
                 2.08 
                 increase 
                 0.0455 
                 1.7 
                 0.00052 
               
               
                 MT1X 
                 3.15 
                 2.08 
                 1.52 
                 increase 
                 0.0167 
                 1.9 
                 0.052 
               
               
                 NFKBIA 
                 2.04 
                 1.07 
                 1.91 
                 increase 
                 0.0167 
                 2.2 
                 0.00014 
               
               
                 SDC4 
                 2.88 
                 1.48 
                 1.95 
                 increase 
                 0.0167 
                 2.2 
                 0.004 
               
               
                 CD14 
                 1.75 
                 0.82 
                 2.14 
                 increase 
                 0.0455 
                 2.4 
                 0.0081 
               
               
                 EGFR 
                 2.02 
                 1.12 
                 1.81 
                 increase 
                 0.0256 
                 2.5 
                 0.00029 
               
               
                 GLDC 
                 1.32 
                 0.70 
                 1.88 
                 increase 
                 0.0256 
                 2.7 
                 0.00087 
               
               
                 IGFBP3 
                 0.44 
                 0.04 
                 11.24 
                 increase 
                 0.0167 
                 2.8 
                 2.70E−05 
               
               
                 GCH1 
                 1.14 
                 0.73 
                 1.55 
                 increase 
                 0.0167 
                 3.3 
                 0.0069 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                 TISSUES_expression_direc- 
                 TISSUES_delta M 
                 TISSUES_Methylation 
                 T-DMR 
               
               
                   
                 Description 
                 tion_in_hypomethylated_tissue 
                 (L − B) 
                 FDR 
                 Location 
               
               
                   
                   
               
               
                   
                 MEF2C 
                 increase 
                 0.74 
                 3.60E−05 
                 Far 
               
               
                   
                 CCK 
                 increase 
                 0.84 
                 4.90E−05 
                 Shore 
               
               
                   
                 NTRK2 
                 increase 
                 0.48 
                 0.0089 
                 Far 
               
               
                   
                 SNCA 
                 increase 
                 0.36 
                 0.0089 
                 Shore 
               
               
                   
                 HSPA8 
                 increase 
                 0.42 
                 0.0089 
                 Shore 
               
               
                   
                 WRB 
                 decrease 
                 −0.52 
                 0.0089 
                 Shore 
               
               
                   
                 PIN 
                 increase 
                 1.1 
                 1.00E−07 
                 Shore 
               
               
                   
                 SOX9 
                 increase 
                 0.77 
                  0.00035 
                 Shore 
               
               
                   
                 KAL1 
                 increase 
                 0.55 
                 0.0017 
                 Shore 
               
               
                   
                 FYN 
                 increase 
                 0.6 
                 0.0012 
                 Shore 
               
               
                   
                 ABCC5 
                 increase 
                 0.93 
                 1.40E−08 
                 Shore 
               
               
                   
                 MTMR6 
                 increase 
                 0.79 
                  0.00025 
                 Far 
               
               
                   
                 SHC1 
                 decrease 
                 1 
                 5.50E−07 
                 Far 
               
               
                   
                 S100A10 
                 increase 
                 −0.49 
                 0.0089 
                 Shore 
               
               
                   
                 IFITM3 
                 increase 
                 −0.56 
                 0.0045 
                 Shore 
               
               
                   
                 IFITM3 
                 increase 
                 −0.56 
                 0.0045 
                 Shore 
               
               
                   
                 DUSP6 
                 decrease 
                 −1.4 
                 9.90E−14 
                 Far 
               
               
                   
                 ACADVL 
                 decrease 
                 0.62 
                 0.0012 
                 Far 
               
               
                   
                 MT2A 
                 increase 
                 −0.91 
                 8.40E−08 
                 Shore 
               
               
                   
                 KCNJ8 
                 increase 
                 −0.58 
                 0.0077 
                 Shore 
               
               
                   
                 MT1X 
                 increase 
                 −0.46 
                 0.0089 
                 Shore 
               
               
                   
                 NFKBIA 
                 increase 
                 −0.69 
                  0.00097 
                 Far 
               
               
                   
                 SDC4 
                 increase 
                 −0.44 
                 0.0089 
                 Shore 
               
               
                   
                 CD14 
                 increase 
                 −0.46 
                 0.0056 
                 Shore 
               
               
                   
                 EGFR 
                 increase 
                 −0.67 
                 3.00E−04 
                 Shore 
               
               
                   
                 GLDC 
                 increase 
                 −0.81 
                  0.00058 
                 Shore 
               
               
                   
                 IGFBP3 
                 increase 
                 0.48 
                 0.0058 
                 Shore 
               
               
                   
                 GCH1 
                 increase 
                 −0.54 
                  0.00053 
                 Shore 
               
               
                   
                   
               
               
                   
                 Data for AZA and HCT116 gene expression data was obtained from Gius et al. (Gius et al., Cancer Cell, 6: 361-71, 2004). 
               
               
                   
                 AZA represents expression data from HCT116 cells treated with 5-aza-2′-deoxycytidine 
               
               
                   
                 TISSUES represents data (methylation and expression) from liver and brain samples examined in the current study. 
               
               
                   
                 L = liver, 
               
               
                   
                 B = brain, 
               
               
                   
                 deltaM is differential methylation 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 Relationship between tissue methylation-specific gene expression and experimental demethylation 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Mean 
                   
                 DKO/ 
                   
                   
                   
                 TISSUES 
               
               
                 Gene 
                 expression 
                 mean 
                 HCT116 
                 DKO_expression_direc- 
                 DKO 
                 TISSUES_Diff_expression 
                 expression 
               
               
                 Description 
                 (DKO) 
                 HCT116 
                 (mean) 
                 tion 
                 p-value 
                 (L − B) 
                 P-value 
               
               
                   
               
               
                 BASP1 
                 1.2362 
                 0.5882 
                 2.1017 
                 increased 
                 0.0014 
                 −5.3 
                 6.10E−07 
               
               
                 TUBA1A 
                 0.9824 
                 0.4569 
                 2.1499 
                 increased 
                 0.0001 
                 −4.1 
                 3.70E−06 
               
               
                 TUBB2B 
                 1.6697 
                 0.5768 
                 2.8949 
                 increased 
                 0 
                 −3.9 
                 2.30E−05 
               
               
                 PRKAR2B 
                 1.4493 
                 0.896 
                 1.6175 
                 increased 
                 0.0064 
                 −3.5 
                 2.00E−05 
               
               
                 TUBB4 
                 2.0428 
                 0.8001 
                 2.5532 
                 increased 
                 0.0057 
                 −3.4 
                 2.90E−05 
               
               
                 YWHAE 
                 1.5439 
                 1.0142 
                 1.5222 
                 increased 
                 0.0276 
                 −2.9 
                 7.60E−05 
               
               
                 YWHAQ 
                 1.6098 
                 0.7673 
                 2.098 
                 increased 
                 0.0191 
                 −2.7 
                 0.00011 
               
               
                 NDUFA5 
                 1.0375 
                 0.6292 
                 1.6489 
                 increased 
                 0.0198 
                 −2.5 
                 0.006  
               
               
                 MAPRE2 
                 1.9434 
                 1.2365 
                 1.5717 
                 increased 
                 0.0264 
                 −2.4 
                 8.40E−06 
               
               
                 HSPA8 
                 1.3072 
                 0.7291 
                 1.7929 
                 increased 
                 0.009 
                 −2.2 
                 0.0015  
               
               
                 NTRK2 
                 1.4017 
                 0.8025 
                 1.7468 
                 increased 
                 0.008 
                 −2.2 
                 0.0041  
               
               
                 STMN1 
                 1.9323 
                 0.9595 
                 2.0139 
                 increased 
                 0.0002 
                 −2.2 
                 0.00012 
               
               
                 PPP2CA 
                 1.905 
                 1.1691 
                 1.6295 
                 increased 
                 0.0476 
                 −2.1 
                 0.0024  
               
               
                 APPBP2 
                 1.8646 
                 1.2318 
                 1.5138 
                 increased 
                 0.0028 
                 −1.9 
                 4.60E−05 
               
               
                 DCK 
                 1.4481 
                 0.85 
                 1.7038 
                 increased 
                 0.0003 
                 −1.9 
                 0.00097 
               
               
                 PIN1 
                 1.5581 
                 0.6673 
                 2.3351 
                 increased 
                 0 
                 −1.8 
                 6.90E−05 
               
               
                 PPP1CB 
                 2.218 
                 1.3206 
                 1.6796 
                 increased 
                 0.0384 
                 −1.5 
                 0.0094  
               
               
                 AP1S2 
                 1.8289 
                 1.0252 
                 1.7839 
                 increased 
                 0.0331 
                 −1.5 
                 0.00045 
               
               
                 TPI1 
                 1.1161 
                 0.6111 
                 1.8266 
                 increased 
                 0.0001 
                 −1.4 
                 0.00055 
               
               
                 AP2B1 
                 1.8708 
                 1.1524 
                 1.6234 
                 increased 
                 0.0106 
                 −1.4 
                 4.50E−05 
               
               
                 FGF12 
                 1.0432 
                 0.5635 
                 1.8512 
                 increased 
                 0.0021 
                 −1.3 
                 0.0048  
               
               
                 SGCE 
                 1.6516 
                 0.7029 
                 2.3498 
                 increased 
                 0.0001 
                 −1.2 
                 0.00054 
               
               
                 CAP1 
                 1.6185 
                 1.021 
                 1.5852 
                 increased 
                 0.0163 
                 −1.2 
                 0.0068  
               
               
                 H2AFX 
                 1.5148 
                 0.954 
                 1.5878 
                 increased 
                 0.0017 
                 −1.1 
                 0.00058 
               
               
                 RAD51C 
                 2.0561 
                 1.1202 
                 1.8354 
                 increased 
                 0.0002 
                 −1 
                 0.0017  
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                 TISSUES_expression_direc- 
                 TISSUES_deltaM 
                 TISSUES_Methylation 
                 T-DMR 
               
               
                   
                 Description 
                 tion_in_hypomethylated_tissue 
                 (L − B) 
                 FDR 
                 Location 
               
               
                   
                   
               
               
                   
                 BASP1 
                 increased 
                 0.5 
                 0.0089 
                 Shore 
               
               
                   
                 TUBA1A 
                 increased 
                 0.69 
                 0.00047 
                 Shore 
               
               
                   
                 TUBB2B 
                 increased 
                 0.53 
                 0.0089 
                 Shore 
               
               
                   
                 PRKAR2B 
                 increased 
                 0.66 
                 0.0089 
                 Far 
               
               
                   
                 TUBB4 
                 increased 
                 0.61 
                 0.00067 
                 Shore 
               
               
                   
                 YWHAE 
                 increased 
                 0.63 
                 0.003 
                 Shore 
               
               
                   
                 YWHAQ 
                 increased 
                 0.52 
                 0.0048 
                 Shore 
               
               
                   
                 NDUFA5 
                 increased 
                 0.66 
                 0.0037 
                 Shore 
               
               
                   
                 MAPRE2 
                 increased 
                 0.53 
                 0.0089 
                 Shore 
               
               
                   
                 HSPA8 
                 increased 
                 0.42 
                 0.0089 
                 Shore 
               
               
                   
                 NTRK2 
                 increased 
                 0.48 
                 0.0089 
                 Far 
               
               
                   
                 STMN1 
                 increased 
                 0.93 
                 3.50E−07 
                 Shore 
               
               
                   
                 PPP2CA 
                 increased 
                 0.66 
                 8.70E−05 
                 Shore 
               
               
                   
                 APPBP2 
                 increased 
                 0.4 
                 0.0089 
                 Shore 
               
               
                   
                 DCK 
                 increased 
                 0.54 
                 0.0089 
                 Far 
               
               
                   
                 PIN1 
                 increased 
                 1.1 
                 1.00E−07 
                 Shore 
               
               
                   
                 PPP1CB 
                 increased 
                 0.54 
                 0.0089 
                 Shore 
               
               
                   
                 AP1S2 
                 increased 
                 0.63 
                 0.0089 
                 Shore 
               
               
                   
                 TPI1 
                 increased 
                 0.45 
                 0.0089 
                 Shore 
               
               
                   
                 AP2B1 
                 increased 
                 0.5 
                 0.0089 
                 Shore 
               
               
                   
                 FGF12 
                 increased 
                 0.67 
                 0.00031 
                 Shore 
               
               
                   
                 SGCE 
                 increased 
                 0.35 
                 0.0089 
                 Shore 
               
               
                   
                 CAP1 
                 increased 
                 0.51 
                 0.0089 
                 Shore 
               
               
                   
                 H2AFX 
                 increased 
                 0.62 
                 0.0013 
                 Shore 
               
               
                   
                 RAD51C 
                 increased 
                 0.59 
                 0.0069 
                 Shore 
               
               
                   
                   
               
               
                   
                 Data for DKO and HCT116 gene expression data was obtained from Gius et al. (Gius et al., Cancer Cell, 6: 361-71, 2004). 
               
               
                   
                 DKO represents expression data from HCT116 cells with a genetic knockout of DNA methylatransferases 1 and 3b 
               
               
                   
                 TISSUES represents data (methylation and expression) from liver and brain samples examined in the current study. 
               
               
                   
                 L = liver, 
               
               
                   
                 B = brain, 
               
               
                   
                 deltaM is differential methylation 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 Regions with tissue-specific differential methylation (T-DMRs) and 
               
               
                 differential methylation in colon cancer (C-DMRs) at a FDR of 5%. 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 Dist 
               
               
                 chr 
                 start 
                 end 
                 tumorstate 
                 similartissue 
                 name 
                 annotation 
                 region 
                 island 
                 To CGI 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 chr10 
                 5774977 
                 5775480 
                 Some methylation 
                 brain 
                 ASB13 
                 NM_024701 
                 upstream 
                 Far 
                 7274 
               
               
                 chr21 
                 37858818 
                 37859555 
                 No methylation 
                 brain 
                 DYRK1A 
                 NM_001396 
                 upstream 
                 Shore 
                 402 
               
               
                 chr11 
                 73980533 
                 73981178 
                 Less methylation 
                 brain 
                 POLD3 
                 NM_006591 
                 downstream 
                 Shore 
                 0 
               
               
                 chr7 
                 92075312 
                 92075873 
                 Less methylation 
                 brain 
                 CDK6 
                 NM_001259 
                 inside 
                 Far 
                 17503 
               
               
                 chr6 
                 168586102 
                 168588777 
                 More methylation 
                 brain 
                 SMOC2 
                 NM_022138 
                 inside 
                 Shore 
                 153 
               
               
                 chr9 
                 137111474 
                 137112189 
                 Less methylation 
                 brain 
                 OLFM1 
                 NM_006334 
                 inside 
                 Far 
                 3926 
               
               
                 chr7 
                 42233455 
                 42234204 
                 More methylation 
                 brain 
                 GLI3 
                 NM_000168 
                 upstream 
                 Shore 
                 0 
               
               
                 chr1 
                 221053963 
                 221054618 
                 Less methylation 
                 brain 
                 FLJ43505 
                 NM_207468 
                 upstream 
                 Shore 
                 249 
               
               
                 chr10 
                 3499370 
                 3500060 
                 No methylation 
                 brain 
                 PITRM1 
                 NM_014889 
                 upstream 
                 Far 
                 8794 
               
               
                 chr19 
                 4505154 
                 4505870 
                 Less methylation 
                 brain 
                 SEMA6B 
                 NM_020241 
                 inside 
                 Shore 
                 1066 
               
               
                 chr12 
                 52430235 
                 52431287 
                 Some methylation 
                 brain 
                 CALCOCO1 
                 NM_020898 
                 upstream 
                 Island 
                 0 
               
               
                 chr6 
                 80711271 
                 80712497 
                 Less methylation 
                 brain 
                 ELOVL4 
                 NM_022726 
                 inside 
                 Shore 
                 966 
               
               
                 chr8 
                 132984463 
                 132985363 
                 Less methylation 
                 brain 
                 KIAA0143 
                 NM_015137 
                 downstream 
                 Shore 
                 141 
               
               
                 chr7 
                 149667145 
                 149668311 
                 More methylation 
                 brain 
                 RARRES2 
                 NM_002889 
                 inside 
                 Shore 
                 81 
               
               
                 chr19 
                 13473726 
                 13475470 
                 Less methylation 
                 brain 
                 CACNA1A 
                 NM_023035 
                 inside 
                 Far 
                 2282 
               
               
                 chr8 
                 3257254 
                 3257862 
                 Less methylation 
                 brain 
                 CSMD1 
                 NM_033225 
                 inside 
                 Far 
                 389899 
               
               
                 chr20 
                 48848947 
                 48849522 
                 More methylation 
                 brain 
                 BCAS4 
                 NM_017843 
                 inside 
                 Far 
                 3398 
               
               
                 chr6 
                 133602937 
                 133603652 
                 More methylation 
                 brain 
                 EYA4 
                 NM_172103 
                 downstream 
                 Shore 
                 127 
               
               
                 chr17 
                 41333049 
                 41334735 
                 Less methylation 
                 brain 
                 MAPT 
                 NM_005910 
                 inside 
                 Far 
                 2213 
               
               
                 chr9 
                 73954546 
                 73955019 
                 No methylation 
                 brain 
                 GDA 
                 NM_004293 
                 inside 
                 Shore 
                 0 
               
               
                 chr20 
                 33336261 
                 33337040 
                 No methylation 
                 brain 
                 FAM83C 
                 NM_178468 
                 overlaps 3′ 
                 Shore 
                 108 
               
               
                 chr1 
                 20383082 
                 20384429 
                 Less methylation 
                 brain 
                 UBXD3 
                 NM_152376 
                 downstream 
                 Shore 
                 518 
               
               
                 chr11 
                 64244495 
                 64245421 
                 Less methylation 
                 brain 
                 NRXN2 
                 NM_015080 
                 inside 
                 Shore 
                 1648 
               
               
                 chr7 
                 121736808 
                 121737526 
                 Some methylation 
                 brain 
                 FEZF1 
                 NM_001024613 
                 upstream 
                 Shore 
                 0 
               
               
                 chr13 
                 20184958 
                 20186542 
                 No methylation 
                 brain 
                 IL17D 
                 NM_138284 
                 inside 
                 Far 
                 7069 
               
               
                 chr10 
                 112248574 
                 112249464 
                 Some methylation 
                 brain 
                 DUSP5 
                 NM_004419 
                 inside 
                 Shore 
                 0 
               
               
                 chrX 
                 120009921 
                 120011075 
                 Less methylation 
                 brain 
                 GLUD2 
                 NM_012084 
                 inside 
                 Shore 
                 270 
               
               
                 chr17 
                 8846444 
                 8846986 
                 Some methylation 
                 brain 
                 NTN1 
                 NM_004822 
                 downstream 
                 Shore 
                 0 
               
               
                 chrX 
                 74062751 
                 74063503 
                 Less methylation 
                 brain 
                 KIAA2022 
                 NM_001008537 
                 upstream 
                 Shore 
                 850 
               
               
                 chr7 
                 142205460 
                 142206135 
                 Some methylation 
                 brain 
                 PRSS2 
                 NM_002770 
                 upstream 
                 Shore 
                 84 
               
               
                 chr15 
                 76344533 
                 76345543 
                 Less methylation 
                 brain 
                 DNAJA4 
                 NM_018602 
                 inside 
                 Shore 
                 0 
               
               
                 chr7 
                 101853738 
                 101854712 
                 More methylation 
                 brain 
                 PRKRIP1 
                 NM_024653 
                 overlaps 5′ 
                 Far 
                 5898 
               
               
                 chr14 
                 102437341 
                 102437847 
                 More methylation 
                 brain 
                 TRAF3 
                 NM_003300 
                 inside 
                 Far 
                 5743 
               
               
                 chr9 
                 37022893 
                 37023922 
                 More methylation 
                 brain 
                 PAX5 
                 NM_016734 
                 inside 
                 Shore 
                 213 
               
               
                 chr10 
                 3818645 
                 3819574 
                 Less methylation 
                 brain 
                 KLF6 
                 NM_001300 
                 upstream 
                 Shore 
                 519 
               
               
                 chr7 
                 12694278 
                 12696066 
                 No methylation 
                 brain 
                 ARL4A 
                 NM_005738 
                 inside 
                 Shore 
                 505 
               
               
                 chr20 
                 47529867 
                 47531270 
                 No methylation 
                 brain 
                 KCNB1 
                 NM_004975 
                 inside 
                 Shore 
                 649 
               
               
                 chr20 
                 49590611 
                 49591553 
                 Some methylation 
                 brain 
                 NFATC2 
                 NM_173091 
                 inside 
                 Shore 
                 758 
               
               
                 chr9 
                 122729717 
                 122730552 
                 More methylation 
                 brain 
                 TRAF1 
                 NM_005658 
                 upstream 
                 Shore 
                 40 
               
               
                 chr10 
                 22807699 
                 22808944 
                 Less methylation 
                 brain 
                 PIP5K2A 
                 NM_005028 
                 downstream 
                 Shore 
                 643 
               
               
                 chr7 
                 38634847 
                 38635894 
                 Less methylation 
                 brain 
                 AMPH 
                 NM_001635 
                 inside 
                 Shore 
                 1070 
               
               
                 chr12 
                 55902867 
                 55903735 
                 More methylation 
                 brain 
                 NXPH4 
                 NM_007224 
                 inside 
                 Shore 
                 1301 
               
               
                 chr19 
                 47263128 
                 47264262 
                 No methylation 
                 brain 
                 GRIK5 
                 NM_002088 
                 upstream 
                 Far 
                 7513 
               
               
                 chr18 
                 68357323 
                 68359390 
                 No methylation 
                 brain 
                 CBLN2 
                 NM_182511 
                 inside 
                 Shore 
                 564 
               
               
                 chr7 
                 92076105 
                 92076398 
                 No methylation 
                 brain 
                 CDK6 
                 NM_001259 
                 inside 
                 Far 
                 18296 
               
               
                 chr15 
                 88348758 
                 88349331 
                 Less methylation 
                 brain 
                 ZNF710 
                 NM_198526 
                 inside 
                 Shore 
                 1843 
               
               
                 chr19 
                 46525737 
                 46526942 
                 Some methylation 
                 brain 
                 TGFB1 
                 NM_000660 
                 downstream 
                 Shore 
                 1912 
               
               
                 chr8 
                 10955476 
                 10957641 
                 Less methylation 
                 brain 
                 XKR6 
                 NM_173683 
                 inside 
                 Shore 
                 969 
               
               
                 chr7 
                 150958618 
                 150959472 
                 Less methylation 
                 brain 
                 PRKAG2 
                 NM_024429 
                 inside 
                 Far 
                 26959 
               
               
                 chr10 
                 49550539 
                 49551086 
                 More methylation 
                 brain 
                 ARHGAP22 
                 NM_021226 
                 upstream 
                 Far 
                 15932 
               
               
                 chr11 
                 63821175 
                 63822065 
                 Some methylation 
                 brain 
                 KCNK4 
                 NM_033310 
                 inside 
                 Shore 
                 1268 
               
               
                 chr16 
                 34067297 
                 34067906 
                 Less methylation 
                 brain 
                 LOC649159 
                 NM_001040069 
                 upstream 
                 Shore 
                 548 
               
               
                 chr7 
                 5224659 
                 5225234 
                 More methylation 
                 brain 
                 WIPI2 
                 NM_001033520 
                 inside 
                 Far 
                 8213 
               
               
                 chr19 
                 14487242 
                 14488698 
                 Less methylation 
                 brain 
                 DNAJB1 
                 NM_006145 
                 inside 
                 Shore 
                 708 
               
               
                 chr6 
                 160690246 
                 160691751 
                 Less methylation 
                 brain 
                 SLC22A3 
                 NM_021977 
                 inside 
                 Shore 
                 0 
               
               
                 chr19 
                 2239906 
                 2240688 
                 More methylation 
                 brain 
                 C19orf35 
                 NM_198532 
                 upstream 
                 Shore 
                 207 
               
               
                 chr10 
                 103579583 
                 103580518 
                 Some methylation 
                 brain 
                 KCNIP2 
                 NM_173194 
                 inside 
                 Island 
                 0 
               
               
                 chr7 
                 121738145 
                 121739034 
                 Some methylation 
                 brain 
                 FEZF1 
                 NM_001024613 
                 upstream 
                 Shore 
                 0 
               
               
                 chr13 
                 101842566 
                 101843905 
                 No methylation 
                 brain 
                 FGF14 
                 NM_175929 
                 inside 
                 Shore 
                 776 
               
               
                 chr2 
                 935104 
                 935722 
                 Some methylation 
                 brain 
                 SNTG2 
                 NM_018968 
                 downstream 
                 Shore 
                 0 
               
               
                 chr2 
                 88531875 
                 88532417 
                 More methylation 
                 brain 
                 FLJ25369 
                 NM_152670 
                 downstream 
                 Shore 
                 33 
               
               
                 chr5 
                 1555785 
                 1556980 
                 More methylation 
                 brain 
                 AYTL2 
                 NM_024830 
                 inside 
                 Far 
                 7498 
               
               
                 chr11 
                 66892179 
                 66893553 
                 More methylation 
                 brain 
                 CLCF1 
                 NM_013246 
                 inside 
                 Far 
                 2910 
               
               
                 chr10 
                 23425480 
                 23426204 
                 No methylation 
                 brain 
                 MSRB2 
                 NM_012228 
                 inside 
                 Shore 
                 396 
               
               
                 chr3 
                 5002243 
                 5003439 
                 Less methylation 
                 brain 
                 BHLHB2 
                 NM_003670 
                 upstream 
                 Shore 
                 0 
               
               
                 chr2 
                 174898625 
                 174899336 
                 More methylation 
                 brain 
                 FLJ46347 
                 NM_001005303 
                 downstream 
                 Shore 
                 0 
               
               
                 chr19 
                 37859830 
                 37860375 
                 More methylation 
                 brain 
                 RGS9BP 
                 NM_207391 
                 inside 
                 Shore 
                 0 
               
               
                 chr15 
                 91430517 
                 91431653 
                 No methylation 
                 brain 
                 RGMA 
                 NM_020211 
                 inside 
                 Shore 
                 779 
               
               
                 chr10 
                 101283725 
                 101284669 
                 Some methylation 
                 brain 
                 NKX2-3 
                 NM_145285 
                 inside 
                 Shore 
                 0 
               
               
                 chr20 
                 9436915 
                 9438354 
                 More methylation 
                 brain 
                 C20orf103 
                 NM_012261 
                 downstream 
                 Shore 
                 1026 
               
               
                 chr15 
                 28985194 
                 28985874 
                 More methylation 
                 brain 
                 KIAA1018 
                 NM_014967 
                 inside 
                 Shore 
                 1510 
               
               
                 chr1 
                 57861340 
                 57861987 
                 Less methylation 
                 brain 
                 DAB1 
                 NM_021080 
                 inside 
                 Far 
                 198115 
               
               
                 chr1 
                 55123414 
                 55124391 
                 Less methylation 
                 brain 
                 DHCR24 
                 NM_014762 
                 inside 
                 Shore 
                 660 
               
               
                 chr18 
                 22385126 
                 22385774 
                 Some methylation 
                 brain 
                 KCTD1 
                 NM_198991 
                 inside 
                 Shore 
                 0 
               
               
                 chr13 
                 111762553 
                 111763273 
                 Some methylation 
                 brain 
                 SOX1 
                 NM_005986 
                 downstream 
                 Shore 
                 87 
               
               
                 chr10 
                 124218023 
                 124218949 
                 Less methylation 
                 brain 
                 HTRA1 
                 NM_002775 
                 inside 
                 Far 
                 5793 
               
               
                 chr13 
                 99424284 
                 99425382 
                 Some methylation 
                 brain 
                 ZIC5 
                 NM_033132 
                 upstream 
                 Shore 
                 1935 
               
               
                 chr13 
                 36147816 
                 36148563 
                 Less methylation 
                 brain 
                 LOC400120 
                 NM_203451 
                 inside 
                 Shore 
                 1353 
               
               
                 chr8 
                 120755795 
                 120756355 
                 Less methylation 
                 brain 
                 ENPP2 
                 NM_001040092 
                 upstream 
                 Far 
                 157624 
               
               
                 chr8 
                 145074517 
                 145075008 
                 More methylation 
                 brain 
                 PLEC1 
                 NM_201384 
                 inside 
                 Shore 
                 394 
               
               
                 chr1 
                 35164297 
                 35165947 
                 Less methylation 
                 brain 
                 ZMYM6 
                 NM_007167 
                 downstream 
                 Shore 
                 1387 
               
               
                 chr5 
                 72958425 
                 72958969 
                 Less methylation 
                 brain 
                 UTP15 
                 NM_032175 
                 upstream 
                 Shore 
                 142 
               
               
                 chr18 
                 42166935 
                 42167750 
                 Some methylation 
                 brain 
                 RNF165 
                 NM_152470 
                 downstream 
                 Shore 
                 0 
               
               
                 chr15 
                 90198817 
                 90201147 
                 Some methylation 
                 brain 
                 SLCO3A1 
                 NM_013272 
                 inside 
                 Shore 
                 131 
               
               
                 chr13 
                 25694712 
                 25696110 
                 No methylation 
                 brain 
                 RNF6 
                 NM_005977 
                 promoter 
                 Shore 
                 0 
               
               
                 chr10 
                 121290732 
                 121291137 
                 More methylation 
                 brain 
                 RGS10 
                 NM_001005339 
                 inside 
                 Shore 
                 331 
               
               
                 chr10 
                 119281507 
                 119283969 
                 Some methylation 
                 brain 
                 EMX2 
                 NM_004098 
                 downstream 
                 Shore 
                 0 
               
               
                 chr2 
                 45010614 
                 45011650 
                 Some methylation 
                 brain 
                 SIX3 
                 NM_005413 
                 downstream 
                 Shore 
                 61 
               
               
                 chr10 
                 101831054 
                 101831872 
                 Less methylation 
                 brain 
                 CPN1 
                 NM_001308 
                 overlaps 5′ 
                 Far 
                 15878 
               
               
                 chr7 
                 2305691 
                 2306476 
                 More methylation 
                 brain 
                 SNX8 
                 NM_013321 
                 inside 
                 Far 
                 13679 
               
               
                 chr20 
                 54635841 
                 54636933 
                 Some methylation 
                 brain 
                 TFAP2C 
                 NM_003222 
                 downstream 
                 inside 
                 0 
               
               
                 chr7 
                 102577345 
                 102577848 
                 No methylation 
                 brain 
                 NAPE-PLD 
                 NM_198990 
                 upstream 
                 Shore 
                 0 
               
               
                 chr20 
                 54632900 
                 54633442 
                 Some methylation 
                 brain 
                 TFAP2C 
                 NM_003222 
                 downstream 
                 Shore 
                 244 
               
               
                 chr6 
                 106657399 
                 106658118 
                 Some methylation 
                 brain 
                 PRDM1 
                 NM_182907 
                 inside 
                 Far 
                 16321 
               
               
                 chr10 
                 89410644 
                 89411916 
                 Less methylation 
                 brain 
                 PAPSS2 
                 NM_001015880 
                 inside 
                 Shore 
                 637 
               
               
                 chr5 
                 139705099 
                 139705722 
                 No methylation 
                 brain 
                 HBEGF 
                 NM_001945 
                 inside 
                 Shore 
                 0 
               
               
                 chr7 
                 55344238 
                 55344779 
                 More methylation 
                 brain 
                 LANCL2 
                 NM_018697 
                 downstream 
                 Far 
                 34680 
               
               
                 chr19 
                 45414041 
                 45414847 
                 Less methylation 
                 brain 
                 TTC9B 
                 NM_152479 
                 inside 
                 Shore 
                 97 
               
               
                 chr16 
                 71648030 
                 71648287 
                 Some methylation 
                 brain 
                 ATBF1 
                 NM_006885 
                 upstream 
                 Shore 
                 728 
               
               
                 chr3 
                 184362174 
                 184362794 
                 More methylation 
                 brain 
                 LAMP3 
                 NM_014398 
                 inside 
                 Shore 
                 174 
               
               
                 chr9 
                 2232790 
                 2233418 
                 No methylation 
                 brain 
                 SMARCA2 
                 NM_003070 
                 upstream 
                 Shore 
                 688 
               
               
                 chr17 
                 35277006 
                 35277374 
                 More methylation 
                 brain 
                 ZPBP2 
                 NM_198844 
                 downstream 
                 Shore 
                 297 
               
               
                 chr2 
                 27336168 
                 27336881 
                 Less methylation 
                 brain 
                 SLC30A3 
                 NM_003459 
                 inside 
                 Shore 
                 1496 
               
               
                 chr6 
                 170702309 
                 170703586 
                 Less methylation 
                 brain 
                 PSMB1 
                 NM_002793 
                 inside 
                 Shore 
                 463 
               
               
                 chr2 
                 100089371 
                 100089913 
                 Less methylation 
                 brain 
                 AFF3 
                 NM_002285 
                 inside 
                 Far 
                 2198 
               
               
                 chr13 
                 32487129 
                 32487948 
                 More methylation 
                 brain 
                 KL 
                 NM_153683 
                 downstream 
                 Shore 
                 0 
               
               
                 chr16 
                 88601552 
                 88602716 
                 More methylation 
                 brain 
                 DBNDD1 
                 NM_024043 
                 inside 
                 Far 
                 3168 
               
               
                 chr17 
                 40746938 
                 40747474 
                 Some methylation 
                 brain 
                 MAP3K14 
                 NM_003954 
                 inside 
                 Far 
                 2200 
               
               
                 chr7 
                 76881860 
                 76882613 
                 More methylation 
                 brain 
                 LOC54103 
                 NM_017439 
                 upstream 
                 Shore 
                 163 
               
               
                 chr9 
                 109287301 
                 109288864 
                 Some methylation 
                 brain 
                 KLF4 
                 NM_004235 
                 inside 
                 Shore 
                 705 
               
               
                 chr19 
                 36536018 
                 36538335 
                 Some methylation 
                 brain 
                 TSHZ3 
                 NM_020856 
                 upstream 
                 Shore 
                 0 
               
               
                 chr19 
                 1811760 
                 1812617 
                 No methylation 
                 brain 
                 KLF16 
                 NM_031918 
                 inside 
                 Shore 
                 94 
               
               
                 chr7 
                 44051835 
                 44052197 
                 Some methylation 
                 brain 
                 DBNL 
                 NM_001014436 
                 inside 
                 Shore 
                 563 
               
               
                 chr13 
                 111760735 
                 111762537 
                 Some methylation 
                 brain 
                 SOX1 
                 NM_005986 
                 downstream 
                 Shore 
                 69 
               
               
                 chr1 
                 243387598 
                 243388628 
                 More methylation 
                 brain 
                 EFCAB2 
                 NM_032328 
                 upstream 
                 Shore 
                 728 
               
               
                 chr11 
                 67008185 
                 67008540 
                 More methylation 
                 brain 
                 AIP 
                 NM_003977 
                 inside 
                 Shore 
                 745 
               
               
                 chr1 
                 3816414 
                 3816740 
                 More methylation 
                 brain 
                 C1orf174 
                 NM_207356 
                 upstream 
                 Far 
                 2098 
               
               
                 chr20 
                 41978520 
                 41978954 
                 Some methylation 
                 brain 
                 C20orf100 
                 NM_032883 
                 inside 
                 Shore 
                 0 
               
               
                 chr4 
                 54663443 
                 54664534 
                 Some methylation 
                 brain 
                 GSH2 
                 NM_133267 
                 upstream 
                 Shore 
                 623 
               
               
                 chr8 
                 101641754 
                 101641969 
                 Less methylation 
                 brain 
                 ANKRD46 
                 NM_198401 
                 upstream 
                 Shore 
                 474 
               
               
                 chr6 
                 10506685 
                 10507236 
                 More methylation 
                 brain 
                 TFAP2A 
                 NM_001032280 
                 inside 
                 Shore 
                 0 
               
               
                 chr9 
                 125811111 
                 125813109 
                 Some methylation 
                 brain 
                 LHX2 
                 NM_004789 
                 downstream 
                 Island 
                 0 
               
               
                 chr2 
                 71358949 
                 71359598 
                 Less methylation 
                 brain 
                 ZNF638 
                 NM_001014972 
                 downstream 
                 Shore 
                 1208 
               
               
                 chr2 
                 50910673 
                 50911104 
                 Less methylation 
                 brain 
                 NRXN1 
                 NM_004801 
                 inside 
                 Far 
                 196922 
               
               
                 chr11 
                 75599856 
                 75600608 
                 More methylation 
                 brain 
                 WNT11 
                 NM_004626 
                 upstream 
                 Island 
                 0 
               
               
                 chr13 
                 111776858 
                 111777751 
                 Some methylation 
                 brain 
                 SOX1 
                 NM_005986 
                 upstream 
                 Shore 
                 438 
               
               
                 chr8 
                 133756854 
                 133758207 
                 No methylation 
                 brain 
                 LRRC6 
                 NM_012472 
                 overlaps 5′ 
                 Island 
                 0 
               
               
                 chr21 
                 43964727 
                 43965443 
                 Less methylation 
                 brain 
                 PDXK 
                 NM_003681 
                 inside 
                 Shore 
                 468 
               
               
                 chr2 
                 65072672 
                 65073755 
                 Less methylation 
                 brain 
                 SLC1A4 
                 NM_003038 
                 inside 
                 Shore 
                 1956 
               
               
                 chr12 
                 112388093 
                 112389548 
                 Some methylation 
                 brain 
                 LHX5 
                 NM_022363 
                 inside 
                 inside 
                 0 
               
               
                 chr11 
                 128070356 
                 128071042 
                 Some methylation 
                 brain 
                 FLI1 
                 NM_002017 
                 inside 
                 Shore 
                 135 
               
               
                 chr7 
                 29814368 
                 29815975 
                 Less methylation 
                 brain 
                 SCRN1 
                 NM_014766 
                 downstream 
                 Shore 
                 1092 
               
               
                 chr13 
                 111767784 
                 111768464 
                 Some methylation 
                 brain 
                 SOX1 
                 NM_005986 
                 downstream 
                 Shore 
                 101 
               
               
                 chr1 
                 110412699 
                 110412994 
                 More methylation 
                 brain 
                 ALX3 
                 NM_006492 
                 inside 
                 inside 
                 0 
               
               
                 chr15 
                 87749926 
                 87751409 
                 Some methylation 
                 brain 
                 RHCG 
                 NM_016321 
                 downstream 
                 Island 
                 0 
               
               
                 chr21 
                 45692055 
                 45692558 
                 Less methylation 
                 brain 
                 COL18A1 
                 NM_130445 
                 inside 
                 Far 
                 6999 
               
               
                 chr4 
                 42096924 
                 42097709 
                 More methylation 
                 brain 
                 ATP8A1 
                 NM_006095 
                 downstream 
                 Shore 
                 1365 
               
               
                 chr10 
                 119295529 
                 119296699 
                 Some methylation 
                 brain 
                 EMX2 
                 NM_004098 
                 inside 
                 Shore 
                 171 
               
               
                 chr18 
                 9902703 
                 9903140 
                 Less methylation 
                 brain 
                 VAPA 
                 NM_194434 
                 downstream 
                 Shore 
                 324 
               
               
                 chr11 
                 119937785 
                 119939272 
                 Less methylation 
                 brain 
                 ARHGEF12 
                 NM_015313 
                 upstream 
                 Shore 
                 760 
               
               
                 chr13 
                 66699432 
                 66700406 
                 Less methylation 
                 brain 
                 PCDH9 
                 NM_020403 
                 inside 
                 Far 
                 2188 
               
               
                 chr21 
                 45319964 
                 45320506 
                 Some methylation 
                 brain 
                 ADARB1 
                 NM_001033049 
                 inside 
                 Shore 
                 64 
               
               
                 chr8 
                 11586977 
                 11587378 
                 Some methylation 
                 brain 
                 GATA4 
                 NM_002052 
                 downstream 
                 Shore 
                 0 
               
               
                 chr14 
                 34941365 
                 34942010 
                 Some methylation 
                 brain 
                 NFKBIA 
                 NM_020529 
                 inside 
                 Shore 
                 788 
               
               
                 chr9 
                 963736 
                 964822 
                 Some methylation 
                 brain 
                 DMRT3 
                 NM_021240 
                 downstream 
                 Shore 
                 460 
               
               
                 chr11 
                 7489950 
                 7490879 
                 Some methylation 
                 brain 
                 PPFIBP2 
                 NM_003621 
                 downstream 
                 Shore 
                 251 
               
               
                 chr9 
                 135226940 
                 135227305 
                 More methylation 
                 brain 
                 SURF4 
                 NM_033161 
                 inside 
                 Far 
                 4822 
               
               
                 chr3 
                 195887111 
                 195887789 
                 More methylation 
                 brain 
                 FAM43A 
                 NM_153690 
                 downstream 
                 Shore 
                 0 
               
               
                 chr11 
                 62449546 
                 62449908 
                 More methylation 
                 brain 
                 CHRM1 
                 NM_000738 
                 upstream 
                 Shore 
                 41 
               
               
                 chr7 
                 5237174 
                 5238382 
                 More methylation 
                 brain 
                 WIPI2 
                 NM_001033520 
                 inside 
                 Far 
                 2538 
               
               
                 chr1 
                 119335409 
                 119336717 
                 Some methylation 
                 brain 
                 TBX15 
                 NM_152380 
                 upstream 
                 Shore 
                 472 
               
               
                 chr7 
                 157176767 
                 157177234 
                 Some methylation 
                 brain 
                 PTPRN2 
                 NM_002847 
                 inside 
                 inside 
                 0 
               
               
                 chr7 
                 99059893 
                 99060630 
                 More methylation 
                 brain 
                 ZNF498 
                 NM_145115 
                 inside 
                 Far 
                 7072 
               
               
                 chr4 
                 99799616 
                 99800611 
                 No methylation 
                 brain 
                 TSPAN5 
                 NM_005723 
                 upstream 
                 Shore 
                 433 
               
               
                 chr1 
                 163470852 
                 163471256 
                 Some methylation 
                 brain 
                 LMX1A 
                 NM_177398 
                 inside 
                 Shore 
                 0 
               
               
                 chr14 
                 72673969 
                 72674259 
                 Less methylation 
                 brain 
                 PSEN1 
                 NM_000021 
                 inside 
                 Shore 
                 469 
               
               
                 chr15 
                 50862519 
                 50863517 
                 More methylation 
                 brain 
                 ONECUT1 
                 NM_004498 
                 inside 
                 Shore 
                 0 
               
               
                 chr7 
                 157748940 
                 157749938 
                 More methylation 
                 brain 
                 PTPRN2 
                 NM_002847 
                 inside 
                 Shore 
                 1574 
               
               
                 chr5 
                 125957145 
                 125958451 
                 No methylation 
                 brain 
                 ALDH7A1 
                 NM_001182 
                 inside 
                 Shore 
                 49 
               
               
                 chr9 
                 137135684 
                 137136292 
                 Less methylation 
                 brain 
                 OLFM1 
                 NM_014279 
                 inside 
                 Shore 
                 899 
               
               
                 chr3 
                 193611789 
                 193611977 
                 Less methylation 
                 brain 
                 FGF12 
                 NM_004113 
                 inside 
                 Shore 
                 1104 
               
               
                 chr3 
                 10834684 
                 10835283 
                 Less methylation 
                 brain 
                 SLC6A11 
                 NM_014229 
                 inside 
                 Shore 
                 1237 
               
               
                 chr3 
                 35654544 
                 35655159 
                 Less methylation 
                 brain 
                 ARPP-21 
                 NM_016300 
                 downstream 
                 Shore 
                 354 
               
               
                 chr4 
                 54669495 
                 54670070 
                 More methylation 
                 brain 
                 GSH2 
                 NM_133267 
                 upstream 
                 Shore 
                 74 
               
               
                 chr11 
                 71467385 
                 71467930 
                 No methylation 
                 brain 
                 NUMA1 
                 NM_006185 
                 inside 
                 Shore 
                 1103 
               
               
                 chr20 
                 61838213 
                 61838785 
                 Some methylation 
                 brain 
                 LIME1 
                 NM_017806 
                 overlaps 3′ 
                 Shore 
                 614 
               
               
                   
               
               
                 Columns are chromosome, start, end, methylation level of tumor, tissue-specificity, gene, annotation, relation to gene, relation to CGI, distance to CGI 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Gene ontology functional categories enriched in hypermethylated C-DMRs 
               
               
                 (P &lt; 0.01) 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 GOBPID 
                 Pvalue 
                 OddsRatio 
                 ExpCount 
                 Count 
                 Size 
                 Term 
                 Region 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 GO:0065007 
                 1.75E−15 
                 1.434797 
                 1049.09 
                 1221 
                 3840 
                 biological 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation 
               
               
                 GO:0006355 
                 2.40E−13 
                 1.500956 
                 504.3282 
                 632 
                 1846 
                 regulation of 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 transcription, 
               
               
                   
                   
                   
                   
                   
                   
                 DNA-dependent 
               
               
                 GO:0022008 
                 1.49E−12 
                 2.556799 
                 66.11453 
                 117 
                 242 
                 neurogenesis 
                 inside/promoter 
               
               
                 GO:0032774 
                 2.03E−12 
                 1.47175 
                 517.4418 
                 641 
                 1894 
                 RNA biosynthetic 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0019219 
                 1.13E−11 
                 1.442249 
                 545.5814 
                 667 
                 1997 
                 regulation of 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 nucleobase, 
               
               
                   
                   
                   
                   
                   
                   
                 nucleoside, 
               
               
                   
                   
                   
                   
                   
                   
                 nucleotide and 
               
               
                   
                   
                   
                   
                   
                   
                 nucleic acid 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0006350 
                 2.42E−11 
                 1.431476 
                 552.1383 
                 672 
                 2021 
                 transcription 
                 inside/promoter 
               
               
                 GO:0010468 
                 9.44E−11 
                 1.410716 
                 569.6231 
                 687 
                 2085 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 gene expression 
               
               
                 GO:0007399 
                 3.96E−10 
                 2.235828 
                 69.90378 
                 116 
                 263 
                 nervous system 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0019222 
                 7.12E−10 
                 1.374211 
                 622.0776 
                 737 
                 2277 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0007275 
                 2.63E−09 
                 1.905658 
                 100.0965 
                 152 
                 395 
                 multicellular 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 organismal 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0050794 
                 2.78E−09 
                 1.36836 
                 612.7722 
                 721 
                 2297 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 cellular process 
               
               
                 GO:0007155 
                 3.54E−09 
                 1.735154 
                 143.9767 
                 204 
                 527 
                 cell adhesion 
                 inside 
               
               
                 GO:0048667 
                 1.03E−08 
                 3.004827 
                 30.59846 
                 59 
                 112 
                 neuron 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                   
                   
                   
                   
                   
                   
                 during 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0031175 
                 2.06E−08 
                 2.788835 
                 33.87686 
                 63 
                 124 
                 neurite 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006366 
                 5.56E−07 
                 1.574135 
                 154.0851 
                 206 
                 564 
                 transcription 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 from RNA 
               
               
                   
                   
                   
                   
                   
                   
                 polymerase II 
               
               
                   
                   
                   
                   
                   
                   
                 promoter 
               
               
                 GO:0048598 
                 6.02E−07 
                 3.034178 
                 22.67564 
                 44 
                 83 
                 embryonic 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0006813 
                 7.63E−07 
                 2.392713 
                 36.60887 
                 63 
                 134 
                 potassium ion 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0048731 
                 2.51E−06 
                 1.509823 
                 163.7593 
                 214 
                 629 
                 system 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0007268 
                 4.80E−06 
                 2.061921 
                 46.00111 
                 73 
                 169 
                 synaptic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transmission 
               
               
                 GO:0001501 
                 6.53E−06 
                 2.073943 
                 43.98528 
                 70 
                 161 
                 skeletal 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0007166 
                 7.82E−06 
                 1.380202 
                 258.195 
                 316 
                 947 
                 cell surface 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 receptor linked 
               
               
                   
                   
                   
                   
                   
                   
                 signal 
               
               
                   
                   
                   
                   
                   
                   
                 transduction 
               
               
                 GO:0048663 
                 8.67E−06 
                 16.02797 
                 3.824807 
                 12 
                 14 
                 neuron fate 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 commitment 
               
               
                 GO:0009887 
                 1.12E−05 
                 1.725707 
                 77.15602 
                 110 
                 283 
                 organ 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0048858 
                 1.20E−05 
                 1.975596 
                 47.81009 
                 74 
                 175 
                 cell projection 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0007411 
                 1.37E−05 
                 3.379597 
                 14.20643 
                 29 
                 52 
                 axon guidance 
                 inside 
               
               
                 GO:0032989 
                 1.71E−05 
                 1.806973 
                 62.01652 
                 91 
                 227 
                 cellular structure 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0007417 
                 1.77E−05 
                 4.033628 
                 4.162579 
                 15 
                 210 
                 central nervous 
                 promoter/inside 
               
               
                   
                   
                   
                   
                   
                   
                 system 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0045165 
                 1.78E−05 
                 5.117343 
                 7.884457 
                 19 
                 29 
                 cell fate 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 commitment 
               
               
                 GO:0050877 
                 3.16E−05 
                 1.457508 
                 153.5387 
                 196 
                 562 
                 neurological 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 system process 
               
               
                 GO:0030182 
                 4.77E−05 
                 4.13478 
                 3.500752 
                 13 
                 180 
                 neuron 
                 promoter/inside 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0003002 
                 6.81E−05 
                 3.011824 
                 14.43907 
                 28 
                 53 
                 regionalization 
                 inside 
               
               
                 GO:0030198 
                 7.50E−05 
                 4.234686 
                 8.469216 
                 19 
                 31 
                 extracellular 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 matrix 
               
               
                   
                   
                   
                   
                   
                   
                 organization and 
               
               
                   
                   
                   
                   
                   
                   
                 biogenesis 
               
               
                 GO:0007165 
                 0.000112 
                 1.27058 
                 370.8697 
                 428 
                 1393 
                 signal 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transduction 
               
               
                 GO:0007498 
                 0.000119 
                 3.462613 
                 10.65482 
                 22 
                 39 
                 mesoderm 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006811 
                 0.000179 
                 1.761983 
                 50.34717 
                 73 
                 186 
                 ion transport 
                 inside/promoter 
               
               
                 GO:0016481 
                 0.000212 
                 1.621181 
                 69.11973 
                 95 
                 253 
                 negative 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 transcription 
               
               
                 GO:0008286 
                 0.000212 
                 4.1309 
                 7.649615 
                 17 
                 28 
                 insulin receptor 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                   
                   
                   
                   
                   
                   
                 pathway 
               
               
                 GO:0007223 
                 0.00022 
                 5.786819 
                 5.19081 
                 13 
                 19 
                 Wnt receptor 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                   
                   
                   
                   
                   
                   
                 pathway, 
               
               
                   
                   
                   
                   
                   
                   
                 calcium 
               
               
                   
                   
                   
                   
                   
                   
                 modulating 
               
               
                   
                   
                   
                   
                   
                   
                 pathway 
               
               
                 GO:0048518 
                 0.000234 
                 1.314643 
                 236.0452 
                 281 
                 864 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 biological 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0007156 
                 0.00028 
                 1.973959 
                 32.23766 
                 50 
                 118 
                 homophilic cell 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 adhesion 
               
               
                 GO:0007409 
                 0.000289 
                 2.697344 
                 14.67244 
                 27 
                 54 
                 axonogenesis 
                 inside/promoter 
               
               
                 GO:0006928 
                 0.000332 
                 1.539749 
                 81.96016 
                 109 
                 300 
                 cell motility 
                 inside 
               
               
                 GO:0000122 
                 0.000357 
                 1.94508 
                 32.51086 
                 50 
                 119 
                 negative 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 transcription 
               
               
                   
                   
                   
                   
                   
                   
                 from RNA 
               
               
                   
                   
                   
                   
                   
                   
                 polymerase II 
               
               
                   
                   
                   
                   
                   
                   
                 promoter 
               
               
                 GO:0051253 
                 0.000364 
                 1.720385 
                 49.72249 
                 71 
                 182 
                 negative 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 RNA metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0048869 
                 0.000389 
                 1.879478 
                 26.48193 
                 44 
                 1336 
                 cellular 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 developmental 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0030901 
                 0.000399 
                 30.11077 
                 0.158574 
                 3 
                 8 
                 midbrain 
                 promoter/inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0019933 
                 0.000447 
                 2.434235 
                 17.21163 
                 30 
                 63 
                 cAMP-mediated 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                 GO:0048523 
                 0.000503 
                 1.381743 
                 142.3193 
                 176 
                 525 
                 negative 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 cellular process 
               
               
                 GO:0009790 
                 0.000527 
                 3.008165 
                 10.78958 
                 21 
                 40 
                 embryonic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0007169 
                 0.000542 
                 3.862582 
                 2.834518 
                 10 
                 143 
                 transmembrane 
                 promoter/inside 
               
               
                   
                   
                   
                   
                   
                   
                 receptor protein 
               
               
                   
                   
                   
                   
                   
                   
                 tyrosine kinase 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                   
                   
                   
                   
                   
                   
                 pathway 
               
               
                 GO:0045941 
                 0.000581 
                 1.568199 
                 68.30013 
                 92 
                 250 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 transcription 
               
               
                 GO:0035107 
                 0.000665 
                 3.174262 
                 9.562018 
                 19 
                 35 
                 appendage 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0060173 
                 0.000665 
                 3.174262 
                 9.562018 
                 19 
                 35 
                 limb 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0035295 
                 0.00079 
                 1.99814 
                 26.22725 
                 41 
                 96 
                 tube 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0009792 
                 0.000941 
                 2.036269 
                 24.04165 
                 38 
                 88 
                 embryonic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                   
                   
                   
                   
                   
                   
                 ending in birth or 
               
               
                   
                   
                   
                   
                   
                   
                 egg hatching 
               
               
                 GO:0006817 
                 0.001021 
                 2.34154 
                 16.39203 
                 28 
                 60 
                 phosphate 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0035270 
                 0.001048 
                 3.649792 
                 7.092567 
                 15 
                 26 
                 endocrine 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 system 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0001709 
                 0.001066 
                 3.642225 
                 7.103214 
                 15 
                 26 
                 cell fate 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 determination 
               
               
                 GO:0030326 
                 0.001093 
                 3.244364 
                 8.469216 
                 17 
                 31 
                 embryonic limb 
                 inside/promoter 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0043583 
                 0.00125 
                 2.813623 
                 10.65482 
                 20 
                 39 
                 ear development 
                 inside 
               
               
                 GO:0051254 
                 0.001323 
                 1.583569 
                 56.00611 
                 76 
                 205 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 RNA metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0001649 
                 0.00135 
                 3.73849 
                 6.556812 
                 14 
                 24 
                 osteoblast 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0016477 
                 0.001648 
                 3.088396 
                 3.84543 
                 11 
                 194 
                 cell migration 
                 promoter 
               
               
                 GO:0001756 
                 0.001671 
                 5.336521 
                 4.098008 
                 10 
                 15 
                 somitogenesis 
                 inside 
               
               
                 GO:0030154 
                 0.001739 
                 1.236387 
                 282.3619 
                 323 
                 1062 
                 cell 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0009953 
                 0.001796 
                 3.338246 
                 7.376414 
                 15 
                 27 
                 dorsal/ventral 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 pattern 
               
               
                   
                   
                   
                   
                   
                   
                 formation 
               
               
                 GO:0007420 
                 0.0018 
                 2.174124 
                 17.64753 
                 29 
                 65 
                 brain 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0031325 
                 0.001905 
                 1.420589 
                 91.79537 
                 116 
                 336 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 cellular 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0031016 
                 0.002219 
                 7.112091 
                 3.005206 
                 8 
                 11 
                 pancreas 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0030878 
                 0.002221 
                 15.99486 
                 1.912404 
                 6 
                 7 
                 thyroid gland 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0045597 
                 0.002287 
                 2.243075 
                 15.57243 
                 26 
                 57 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of cell 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0042472 
                 0.002303 
                 3.398158 
                 6.830013 
                 14 
                 25 
                 inner ear 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0001654 
                 0.002407 
                 2.671956 
                 10.38162 
                 19 
                 38 
                 eye 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0048534 
                 0.002449 
                 1.718494 
                 34.96967 
                 50 
                 128 
                 hemopoietic or 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 lymphoid organ 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0001764 
                 0.002689 
                 2.838035 
                 9.015617 
                 17 
                 33 
                 neuron 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 migration 
               
               
                 GO:0009653 
                 0.002713 
                 1.700625 
                 35.04919 
                 50 
                 132 
                 anatomical 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 structure 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0007267 
                 0.002732 
                 1.482421 
                 66.00984 
                 86 
                 245 
                 cell-cell signaling 
                 inside 
               
               
                 GO:0045944 
                 0.002991 
                 1.705597 
                 34.42327 
                 49 
                 126 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 transcription 
               
               
                   
                   
                   
                   
                   
                   
                 from RNA 
               
               
                   
                   
                   
                   
                   
                   
                 polymerase II 
               
               
                   
                   
                   
                   
                   
                   
                 promoter 
               
               
                 GO:0048666 
                 0.003085 
                 4.51368 
                 4.323974 
                 10 
                 16 
                 neuron 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006812 
                 0.003153 
                 1.368558 
                 103.8162 
                 128 
                 380 
                 cation transport 
                 inside 
               
               
                 GO:0007507 
                 0.003355 
                 2.047192 
                 18.26662 
                 29 
                 67 
                 heart 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0003007 
                 0.003369 
                 4.446488 
                 4.371208 
                 10 
                 16 
                 heart 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0048513 
                 0.003421 
                 1.838106 
                 17.14586 
                 29 
                 865 
                 organ 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0042311 
                 0.003551 
                 11.5716 
                 0.317149 
                 3 
                 16 
                 vasodilation 
                 promoter 
               
               
                 GO:0030855 
                 0.003746 
                 3.114549 
                 7.103214 
                 14 
                 26 
                 epithelial cell 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0045761 
                 0.004025 
                 2.670723 
                 9.288818 
                 17 
                 34 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 adenylate 
               
               
                   
                   
                   
                   
                   
                   
                 cyclase activity 
               
               
                 GO:0007595 
                 0.004249 
                 10.74396 
                 0.336971 
                 3 
                 17 
                 lactation 
                 promoter 
               
               
                 GO:0007369 
                 0.004843 
                 3.66869 
                 5.19081 
                 11 
                 19 
                 gastrulation 
                 inside 
               
               
                 GO:0030902 
                 0.004843 
                 3.66869 
                 5.19081 
                 11 
                 19 
                 hindbrain 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0001935 
                 0.005025 
                 10.02667 
                 0.356792 
                 3 
                 18 
                 endothelial cell 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 proliferation 
               
               
                 GO:0042136 
                 0.005064 
                 5.333333 
                 3.278406 
                 8 
                 12 
                 neurotransmitter 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 biosynthetic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0048839 
                 0.005371 
                 6.288015 
                 0.713585 
                 4 
                 36 
                 inner ear 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0002052 
                 0.005562 
                 Inf 
                 1.092802 
                 4 
                 4 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 neuroblast 
               
               
                   
                   
                   
                   
                   
                   
                 proliferation 
               
               
                 GO:0009249 
                 0.005562 
                 Inf 
                 1.092802 
                 4 
                 4 
                 protein 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 lipoylation 
               
               
                 GO:0021871 
                 0.005562 
                 Inf 
                 1.092802 
                 4 
                 4 
                 forebrain 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regionalization 
               
               
                 GO:0045885 
                 0.005562 
                 Inf 
                 1.092802 
                 4 
                 4 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 survival gene 
               
               
                   
                   
                   
                   
                   
                   
                 product activity 
               
               
                 GO:0001505 
                 0.005663 
                 1.970186 
                 18.03123 
                 28 
                 66 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 neurotransmitter 
               
               
                   
                   
                   
                   
                   
                   
                 levels 
               
               
                 GO:0048732 
                 0.005765 
                 2.527244 
                 9.547686 
                 17 
                 35 
                 gland 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006814 
                 0.005976 
                 1.839114 
                 22.12924 
                 33 
                 81 
                 sodium ion 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0006023 
                 0.006192 
                 3.81075 
                 4.644409 
                 10 
                 17 
                 aminoglycan 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 biosynthetic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0042127 
                 0.006293 
                 1.345211 
                 97.53259 
                 119 
                 357 
                 regulation of cell 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 proliferation 
               
               
                 GO:0030324 
                 0.006442 
                 2.403541 
                 10.38162 
                 18 
                 38 
                 lung 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0002062 
                 0.006821 
                 7.996328 
                 2.185604 
                 6 
                 8 
                 chondrocyte 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0040018 
                 0.006821 
                 7.996328 
                 2.185604 
                 6 
                 8 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 multicellular 
               
               
                   
                   
                   
                   
                   
                   
                 organism growth 
               
               
                 GO:0007611 
                 0.006957 
                 2.306642 
                 11.20122 
                 19 
                 41 
                 learning and/or 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 memory 
               
               
                 GO:0045661 
                 0.007037 
                 13.32416 
                 1.639203 
                 5 
                 6 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 myoblast 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0045773 
                 0.007037 
                 13.32416 
                 1.639203 
                 5 
                 6 
                 positive 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 axon extension 
               
               
                 GO:0007154 
                 0.007222 
                 1.475146 
                 52.15117 
                 68 
                 2631 
                 cell 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 communication 
               
               
                 GO:0009880 
                 0.007599 
                 2.891016 
                 6.830013 
                 13 
                 25 
                 embryonic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 pattern 
               
               
                   
                   
                   
                   
                   
                   
                 specification 
               
               
                 GO:0030321 
                 0.007689 
                 19.97143 
                 0.138753 
                 2 
                 7 
                 transepithelial 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0031018 
                 0.007689 
                 19.97143 
                 0.138753 
                 2 
                 7 
                 endocrine 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 pancreas 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0008015 
                 0.007821 
                 3.285874 
                 2.279507 
                 7 
                 115 
                 blood circulation 
                 promoter 
               
               
                 GO:0000165 
                 0.008109 
                 1.644346 
                 30.87166 
                 43 
                 113 
                 MAPKKK cascade 
                 inside 
               
               
                 GO:0007215 
                 0.008131 
                 3.260608 
                 5.46401 
                 11 
                 20 
                 glutamate 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                   
                   
                   
                   
                   
                   
                 pathway 
               
               
                 GO:0051056 
                 0.008464 
                 1.474653 
                 50.8153 
                 66 
                 186 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 small GTPase 
               
               
                   
                   
                   
                   
                   
                   
                 mediated signal 
               
               
                   
                   
                   
                   
                   
                   
                 transduction 
               
               
                 GO:0007204 
                 0.008553 
                 5.435497 
                 0.812694 
                 4 
                 41 
                 elevation of 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 cytosolic calcium 
               
               
                   
                   
                   
                   
                   
                   
                 ion 
               
               
                   
                   
                   
                   
                   
                   
                 concentration 
               
               
                 GO:0006936 
                 0.008566 
                 3.225464 
                 2.319151 
                 7 
                 117 
                 muscle 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 contraction 
               
               
                 GO:0040011 
                 0.008827 
                 1.964954 
                 16.11883 
                 25 
                 59 
                 locomotion 
                 inside 
               
               
                 GO:0030900 
                 0.008854 
                 2.292153 
                 10.64347 
                 18 
                 39 
                 forebrain 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0031324 
                 0.009247 
                 1.322222 
                 98.62539 
                 119 
                 361 
                 negative 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 regulation of 
               
               
                   
                   
                   
                   
                   
                   
                 cellular 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0042592 
                 0.009255 
                 1.337753 
                 90.42937 
                 110 
                 331 
                 homeostatic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0002009 
                 0.009685 
                 2.920795 
                 6.26769 
                 12 
                 23 
                 morphogenesis 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 of an epithelium 
               
               
                 GO:0001656 
                 0.009895 
                 2.910563 
                 6.283612 
                 12 
                 23 
                 metanephros 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0042445 
                 0.00997 
                 2.136582 
                 12.29402 
                 20 
                 45 
                 hormone 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 Gene ontology functional categories enriched in hypomethylated C-DMRs 
               
               
                 (P &lt; 0.01) 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 GOBPID 
                 Pvalue 
                 OddsRatio 
                 ExpCount 
                 Count 
                 Size 
                 Term 
                 Region 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 GO:0032501 
                 7.53E−07 
                 1.311239 
                 504.7175 
                 590 
                 2357 
                 multicellular 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 organismal process 
               
               
                 GO:0007155 
                 2.18E−06 
                 1.601385 
                 112.8494 
                 157 
                 527 
                 cell adhesion 
                 inside 
               
               
                 GO:0032502 
                 5.33E−05 
                 1.245694 
                 503.4327 
                 572 
                 2351 
                 developmental 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0006816 
                 9.88E−05 
                 2.422182 
                 18.41566 
                 34 
                 86 
                 calcium ion 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0007165 
                 0.000127 
                 1.308432 
                 258.2146 
                 308 
                 1226 
                 signal transduction 
                 inside 
               
               
                 GO:0009887 
                 0.000132 
                 1.632507 
                 64.02653 
                 91 
                 299 
                 organ 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0051056 
                 0.000185 
                 1.814148 
                 39.82921 
                 61 
                 186 
                 regulation of small 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 GTPase mediated 
               
               
                   
                   
                   
                   
                   
                   
                 signal transduction 
               
               
                 GO:0007399 
                 0.000207 
                 1.405645 
                 134.4771 
                 171 
                 628 
                 nervous system 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0048731 
                 0.000231 
                 1.401666 
                 134.76 
                 171 
                 641 
                 system 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006812 
                 0.000257 
                 1.522005 
                 81.37151 
                 110 
                 380 
                 cation transport 
                 inside 
               
               
                 GO:0007154 
                 0.000309 
                 1.636925 
                 55.3083 
                 79 
                 271 
                 cell communication 
                 inside 
               
               
                 GO:0006817 
                 0.00031 
                 2.64056 
                 12.84813 
                 25 
                 60 
                 phosphate 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0048667 
                 0.000336 
                 2.058652 
                 23.98318 
                 40 
                 112 
                 neuron 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                   
                   
                   
                   
                   
                   
                 during 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0007409 
                 0.00043 
                 2.069855 
                 22.69837 
                 38 
                 106 
                 axonogenesis 
                 inside 
               
               
                 GO:0001525 
                 0.000486 
                 2.076003 
                 22.05596 
                 37 
                 103 
                 angiogenesis 
                 inside 
               
               
                 GO:0003015 
                 0.000486 
                 3.163871 
                 8.351286 
                 18 
                 39 
                 heart process 
                 inside 
               
               
                 GO:0032989 
                 0.000504 
                 1.657806 
                 48.60877 
                 70 
                 227 
                 cellular structure 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0035023 
                 0.000542 
                 2.353129 
                 15.41776 
                 28 
                 72 
                 regulation of Rho 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 protein signal 
               
               
                   
                   
                   
                   
                   
                   
                 transduction 
               
               
                 GO:0030879 
                 0.000937 
                 7.363679 
                 2.569627 
                 8 
                 12 
                 mammary gland 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0008016 
                 0.001128 
                 3.10623 
                 7.494744 
                 16 
                 35 
                 regulation of heart 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 contraction 
               
               
                 GO:0006811 
                 0.001488 
                 2.18175 
                 15.51374 
                 27 
                 74 
                 ion transport 
                 inside 
               
               
                 GO:0031175 
                 0.001662 
                 1.828747 
                 26.55281 
                 41 
                 124 
                 neurite 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0006820 
                 0.001971 
                 1.806743 
                 26.76694 
                 41 
                 125 
                 anion transport 
                 inside 
               
               
                 GO:0048858 
                 0.002059 
                 1.654343 
                 37.47372 
                 54 
                 175 
                 cell projection 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 morphogenesis 
               
               
                 GO:0050801 
                 0.002091 
                 1.644364 
                 38.33026 
                 55 
                 179 
                 ion homeostasis 
                 inside 
               
               
                 GO:0001568 
                 0.002126 
                 1.768872 
                 28.48003 
                 43 
                 133 
                 blood vessel 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0048661 
                 0.002212 
                 18.39035 
                 1.284813 
                 5 
                 6 
                 positive regulation 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 of smooth muscle 
               
               
                   
                   
                   
                   
                   
                   
                 cell proliferation 
               
               
                 GO:0007268 
                 0.002312 
                 1.542972 
                 50.32185 
                 69 
                 235 
                 synaptic 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transmission 
               
               
                 GO:0006813 
                 0.002495 
                 1.749208 
                 28.69416 
                 43 
                 134 
                 potassium ion 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transport 
               
               
                 GO:0030324 
                 0.00321 
                 2.681625 
                 8.137151 
                 16 
                 38 
                 lung development 
                 inside 
               
               
                 GO:0050877 
                 0.003314 
                 1.32209 
                 120.3442 
                 147 
                 562 
                 neurological system 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0006029 
                 0.003629 
                 10.84488 
                 0.312344 
                 3 
                 30 
                 proteoglycan 
                 promoter 
               
               
                   
                   
                   
                   
                   
                   
                 metabolic process 
               
               
                 GO:0051147 
                 0.004404 
                 7.357712 
                 1.92722 
                 6 
                 9 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 muscle cell 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0008299 
                 0.005816 
                 5.151501 
                 2.569627 
                 7 
                 12 
                 isoprenoid 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 biosynthetic 
               
               
                   
                   
                   
                   
                   
                   
                 process 
               
               
                 GO:0007265 
                 0.005855 
                 1.529967 
                 41.75643 
                 57 
                 195 
                 Ras protein signal 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 transduction 
               
               
                 GO:0005513 
                 0.006372 
                 9.194002 
                 1.498949 
                 5 
                 7 
                 detection of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 calcium ion 
               
               
                 GO:0009395 
                 0.006372 
                 9.194002 
                 1.498949 
                 5 
                 7 
                 phospholipid 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 catabolic process 
               
               
                 GO:0003001 
                 0.007507 
                 2.029051 
                 13.2764 
                 22 
                 62 
                 generation of a 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signal involved in 
               
               
                   
                   
                   
                   
                   
                   
                 cell-cell signaling 
               
               
                 GO:0043062 
                 0.008118 
                 1.973458 
                 14.13295 
                 23 
                 66 
                 extracellular 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 structure 
               
               
                   
                   
                   
                   
                   
                   
                 organization and 
               
               
                   
                   
                   
                   
                   
                   
                 biogenesis 
               
               
                 GO:0007528 
                 0.009022 
                 5.517581 
                 2.141355 
                 6 
                 10 
                 neuromuscular 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 junction 
               
               
                   
                   
                   
                   
                   
                   
                 development 
               
               
                 GO:0007613 
                 0.009022 
                 5.517581 
                 2.141355 
                 6 
                 10 
                 memory 
                 inside 
               
               
                 GO:0045884 
                 0.009022 
                 5.517581 
                 2.141355 
                 6 
                 10 
                 regulation of 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 survival gene 
               
               
                   
                   
                   
                   
                   
                   
                 product expression 
               
               
                 GO:0048659 
                 0.009022 
                 5.517581 
                 2.141355 
                 6 
                 10 
                 smooth muscle cell 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 proliferation 
               
               
                 GO:0007242 
                 0.0098 
                 1.194127 
                 242.8297 
                 274 
                 1134 
                 intracellular 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 signaling cascade 
               
               
                 GO:0030949 
                 0.009808 
                 Inf 
                 0.642407 
                 3 
                 3 
                 positive regulation 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 of vascular 
               
               
                   
                   
                   
                   
                   
                   
                 endothelial growth 
               
               
                   
                   
                   
                   
                   
                   
                 factor receptor 
               
               
                   
                   
                   
                   
                   
                   
                 signaling pathway 
               
               
                 GO:0035313 
                 0.009808 
                 Inf 
                 0.642407 
                 3 
                 3 
                 wound healing, 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 spreading of 
               
               
                   
                   
                   
                   
                   
                   
                 epidermal cells 
               
               
                 GO:0045662 
                 0.009808 
                 Inf 
                 0.642407 
                 3 
                 3 
                 negative regulation 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 of myoblast 
               
               
                   
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 GO:0045740 
                 0.009808 
                 Inf 
                 0.642407 
                 3 
                 3 
                 positive regulation 
                 inside 
               
               
                   
                   
                   
                   
                   
                   
                 of DNA replication 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 Regions with Tissue-Specific Differential Methylation 
               
               
                 (T-DMRs) at a FDR of 5% in mus musculus. 
               
            
           
           
               
               
               
               
            
               
                   
                 chromosome 
                 start 
                 end 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 chr10 
                 126979292 
                 126980671 
               
               
                   
                 chr10 
                 127656871 
                 127658217 
               
               
                   
                 chr10 
                 24887401 
                 24889329 
               
               
                   
                 chr10 
                 28888124 
                 28888716 
               
               
                   
                 chr10 
                 33988268 
                 33988975 
               
               
                   
                 chr10 
                 53437662 
                 53438762 
               
               
                   
                 chr10 
                 67306310 
                 67306619 
               
               
                   
                 chr10 
                 76555574 
                 76556749 
               
               
                   
                 chr10 
                 79735316 
                 79736395 
               
               
                   
                 chr11 
                 100635649 
                 100638591 
               
               
                   
                 chr11 
                 102212266 
                 102212933 
               
               
                   
                 chr11 
                 115107596 
                 115109335 
               
               
                   
                 chr11 
                 115111691 
                 115113355 
               
               
                   
                 chr11 
                 120394702 
                 120395960 
               
               
                   
                 chr1 
                 134507754 
                 134508470 
               
               
                   
                 chr11 
                 3811935 
                 3812582 
               
               
                   
                 chr1 
                 157570104 
                 157573766 
               
               
                   
                 chr11 
                 57912170 
                 57913262 
               
               
                   
                 chr1 
                 158417149 
                 158418321 
               
               
                   
                 chr11 
                 58766015 
                 58766738 
               
               
                   
                 chr11 
                 59954757 
                 59955965 
               
               
                   
                 chr1 
                 162825603 
                 162826433 
               
               
                   
                 chr1 
                 162979500 
                 162980205 
               
               
                   
                 chr11 
                 63695421 
                 63696067 
               
               
                   
                 chr11 
                 70847335 
                 70849134 
               
               
                   
                 chr11 
                 78365131 
                 78365880 
               
               
                   
                 chr11 
                 79408077 
                 79409420 
               
               
                   
                 chr11 
                 81782037 
                 81782297 
               
               
                   
                 chr11 
                 83112200 
                 83113213 
               
               
                   
                 chr11 
                 84336675 
                 84338372 
               
               
                   
                 chr1 
                 186509025 
                 186510266 
               
               
                   
                 chr1 
                 186697870 
                 186699731 
               
               
                   
                 chr1 
                 193522768 
                 193523343 
               
               
                   
                 chr11 
                 98586369 
                 98587025 
               
               
                   
                 chr11 
                 98587096 
                 98589090 
               
               
                   
                 chr12 
                 108421230 
                 108422853 
               
               
                   
                 chr12 
                 113167928 
                 113169389 
               
               
                   
                 chr12 
                 30114031 
                 30115188 
               
               
                   
                 chr12 
                 30240986 
                 30242545 
               
               
                   
                 chr12 
                 31879295 
                 31880075 
               
               
                   
                 chr12 
                 53621042 
                 53623143 
               
               
                   
                 chr12 
                 55778410 
                 55779489 
               
               
                   
                 chr12 
                 58362526 
                 58363068 
               
               
                   
                 chr12 
                 60013490 
                 60014134 
               
               
                   
                 chr12 
                 70826084 
                 70826557 
               
               
                   
                 chr12 
                 70827383 
                 70827994 
               
               
                   
                 chr12 
                 71143556 
                 71145601 
               
               
                   
                 chr12 
                 71263656 
                 71264508 
               
               
                   
                 chr12 
                 73151554 
                 73155106 
               
               
                   
                 chr12 
                 83257544 
                 83259350 
               
               
                   
                 chr12 
                 99300922 
                 99301356 
               
               
                   
                 chr13 
                 49157646 
                 49158486 
               
               
                   
                 chr13 
                 52165707 
                 52166249 
               
               
                   
                 chr13 
                 55162752 
                 55164518 
               
               
                   
                 chr13 
                 55477782 
                 55479287 
               
               
                   
                 chr13 
                 58353772 
                 58354380 
               
               
                   
                 chr13 
                 58818797 
                 58820212 
               
               
                   
                 chr13 
                 70203147 
                 70204256 
               
               
                   
                 chr13 
                 70633047 
                 70633499 
               
               
                   
                 chr14 
                 102537320 
                 102538579 
               
               
                   
                 chr14 
                 104219050 
                 104219694 
               
               
                   
                 chr14 
                 20310849 
                 20311379 
               
               
                   
                 chr14 
                 24418637 
                 24419041 
               
               
                   
                 chr14 
                 30097079 
                 30098320 
               
               
                   
                 chr14 
                 50925011 
                 50925826 
               
               
                   
                 chr14 
                 53864878 
                 53866395 
               
               
                   
                 chr14 
                 54043521 
                 54045533 
               
               
                   
                 chr14 
                 54515663 
                 54516328 
               
               
                   
                 chr14 
                 64214773 
                 64215654 
               
               
                   
                 chr14 
                 84989766 
                 84990308 
               
               
                   
                 chr15 
                 100321886 
                 100322823 
               
               
                   
                 chr15 
                 101114047 
                 101116123 
               
               
                   
                 chr15 
                 102016174 
                 102017697 
               
               
                   
                 chr15 
                 102321308 
                 102321977 
               
               
                   
                 chr15 
                 27417171 
                 27417674 
               
               
                   
                 chr15 
                 27968069 
                 27968486 
               
               
                   
                 chr15 
                 39684465 
                 39687107 
               
               
                   
                 chr15 
                 68759467 
                 68761004 
               
               
                   
                 chr15 
                 68761548 
                 68763148 
               
               
                   
                 chr15 
                 78543180 
                 78543923 
               
               
                   
                 chr15 
                 79602362 
                 79603288 
               
               
                   
                 chr15 
                 82533583 
                 82534176 
               
               
                   
                 chr15 
                 85508940 
                 85510281 
               
               
                   
                 chr15 
                 85564473 
                 85565120 
               
               
                   
                 chr15 
                 89202174 
                 89205204 
               
               
                   
                 chr15 
                 91204682 
                 91205405 
               
               
                   
                 chr15 
                 96467000 
                 96469097 
               
               
                   
                 chr15 
                 96570462 
                 96571826 
               
               
                   
                 chr16 
                 24114726 
                 24115655 
               
               
                   
                 chr16 
                 32564545 
                 32567256 
               
               
                   
                 chr16 
                 42108443 
                 42109471 
               
               
                   
                 chr16 
                 85052975 
                 85055043 
               
               
                   
                 chr17 
                 12502541 
                 12503011 
               
               
                   
                 chr17 
                 27384570 
                 27385268 
               
               
                   
                 chr17 
                 28786279 
                 28786821 
               
               
                   
                 chr17 
                 34443844 
                 34444281 
               
               
                   
                 chr17 
                 34739247 
                 34740179 
               
               
                   
                 chr17 
                 56073635 
                 56074076 
               
               
                   
                 chr17 
                 63187176 
                 63187802 
               
               
                   
                 chr17 
                 73446574 
                 73447083 
               
               
                   
                 chr17 
                 73983627 
                 73984097 
               
               
                   
                 chr17 
                 80466736 
                 80468474 
               
               
                   
                 chr17 
                 84696081 
                 84698211 
               
               
                   
                 chr18 
                 25868426 
                 25868929 
               
               
                   
                 chr18 
                 34988882 
                 34989739 
               
               
                   
                 chr18 
                 36789615 
                 36790328 
               
               
                   
                 chr18 
                 37945287 
                 37947408 
               
               
                   
                 chr18 
                 38992510 
                 38993187 
               
               
                   
                 chr18 
                 60729232 
                 60731679 
               
               
                   
                 chr18 
                 61044585 
                 61044998 
               
               
                   
                 chr18 
                 65349251 
                 65349859 
               
               
                   
                 chr18 
                 75560629 
                 75561096 
               
               
                   
                 chr1 
                 91413137 
                 91414588 
               
               
                   
                 chr19 
                 25178728 
                 25179405 
               
               
                   
                 chr19 
                 34813801 
                 34814130 
               
               
                   
                 chr19 
                 44354649 
                 44355473 
               
               
                   
                 chr19 
                 45043522 
                 45045155 
               
               
                   
                 chr19 
                 46817593 
                 46818555 
               
               
                   
                 chr19 
                 54252753 
                 54254455 
               
               
                   
                 chr19 
                 55802705 
                 55803957 
               
               
                   
                 chr19 
                 5955473 
                 5957745 
               
               
                   
                 chr19 
                 8906711 
                 8907458 
               
               
                   
                 chr2 
                 104208681 
                 104210622 
               
               
                   
                 chr2 
                 130849724 
                 130850548 
               
               
                   
                 chr2 
                 163238725 
                 163239474 
               
               
                   
                 chr2 
                 179955182 
                 179957788 
               
               
                   
                 chr2 
                 33190742 
                 33192554 
               
               
                   
                 chr2 
                 65841897 
                 65843222 
               
               
                   
                 chr2 
                 93621671 
                 93622925 
               
               
                   
                 chr3 
                 121522532 
                 121522894 
               
               
                   
                 chr3 
                 121522949 
                 121524010 
               
               
                   
                 chr3 
                 121802762 
                 121803376 
               
               
                   
                 chr3 
                 127151720 
                 127152797 
               
               
                   
                 chr3 
                 135373833 
                 135375158 
               
               
                   
                 chr3 
                 83096129 
                 83096809 
               
               
                   
                 chr3 
                 83137592 
                 83139735 
               
               
                   
                 chr3 
                 87004578 
                 87005432 
               
               
                   
                 chr4 
                 117381676 
                 117383055 
               
               
                   
                 chr4 
                 125561574 
                 125562182 
               
               
                   
                 chr4 
                 136994230 
                 136995186 
               
               
                   
                 chr4 
                 138238001 
                 138239488 
               
               
                   
                 chr4 
                 148063477 
                 148065006 
               
               
                   
                 chr4 
                 150869280 
                 150870206 
               
               
                   
                 chr4 
                 154185273 
                 154188604 
               
               
                   
                 chr4 
                 35285562 
                 35286638 
               
               
                   
                 chr4 
                 42972011 
                 42973852 
               
               
                   
                 chr4 
                 42973973 
                 42974614 
               
               
                   
                 chr4 
                 59310854 
                 59311432 
               
               
                   
                 chr4 
                 98613661 
                 98614914 
               
               
                   
                 chr5 
                 107645478 
                 107646164 
               
               
                   
                 chr5 
                 113458417 
                 113459346 
               
               
                   
                 chr5 
                 115071773 
                 115072276 
               
               
                   
                 chr5 
                 124865500 
                 124866267 
               
               
                   
                 chr5 
                 143070755 
                 143071267 
               
               
                   
                 chr5 
                 143233197 
                 143234288 
               
               
                   
                 chr5 
                 65627192 
                 65629135 
               
               
                   
                 chr5 
                 90008195 
                 90009248 
               
               
                   
                 chr6 
                 101163944 
                 101165305 
               
               
                   
                 chr6 
                 119284067 
                 119284606 
               
               
                   
                 chr6 
                 124825932 
                 124826609 
               
               
                   
                 chr6 
                 147219158 
                 147219979 
               
               
                   
                 chr6 
                 38843094 
                 38844092 
               
               
                   
                 chr6 
                 55608676 
                 55609270 
               
               
                   
                 chr6 
                 83108264 
                 83109323 
               
               
                   
                 chr6 
                 83150997 
                 83151731 
               
               
                   
                 chr6 
                 83403666 
                 83405735 
               
               
                   
                 chr6 
                 85995461 
                 85996279 
               
               
                   
                 chr6 
                 90432664 
                 90433797 
               
               
                   
                 chr7 
                 113850061 
                 113850390 
               
               
                   
                 chr7 
                 121496715 
                 121497551 
               
               
                   
                 chr7 
                 127061589 
                 127063103 
               
               
                   
                 chr7 
                 127063311 
                 127064541 
               
               
                   
                 chr7 
                 130484240 
                 130486315 
               
               
                   
                 chr7 
                 139037295 
                 139038319 
               
               
                   
                 chr7 
                 140624014 
                 140624754 
               
               
                   
                 chr7 
                 140757459 
                 140759046 
               
               
                   
                 chr7 
                 15951594 
                 15952451 
               
               
                   
                 chr7 
                 18081819 
                 18082463 
               
               
                   
                 chr7 
                 24596110 
                 24596727 
               
               
                   
                 chr7 
                 24954217 
                 24954966 
               
               
                   
                 chr7 
                 26968540 
                 26971209 
               
               
                   
                 chr7 
                 27442446 
                 27443207 
               
               
                   
                 chr7 
                 29225581 
                 29226432 
               
               
                   
                 chr7 
                 30151377 
                 30151814 
               
               
                   
                 chr7 
                 30822453 
                 30823520 
               
               
                   
                 chr7 
                 45652166 
                 45653161 
               
               
                   
                 chr7 
                 49647288 
                 49647932 
               
               
                   
                 chr7 
                 55711682 
                 55712182 
               
               
                   
                 chr7 
                 79389572 
                 79390003 
               
               
                   
                 chr7 
                 96825159 
                 96825599 
               
               
                   
                 chr8 
                 111425321 
                 111427570 
               
               
                   
                 chr8 
                 111588936 
                 111589513 
               
               
                   
                 chr8 
                 111633592 
                 111634305 
               
               
                   
                 chr8 
                 112137088 
                 112141065 
               
               
                   
                 chr8 
                 112859398 
                 112860273 
               
               
                   
                 chr8 
                 124619935 
                 124620738 
               
               
                   
                 chr8 
                 4257372 
                 4258328 
               
               
                   
                 chr8 
                 47706238 
                 47707539 
               
               
                   
                 chr8 
                 48784788 
                 48786354 
               
               
                   
                 chr8 
                 87673614 
                 87674328 
               
               
                   
                 chr8 
                 87782082 
                 87783422 
               
               
                   
                 chr9 
                 106313871 
                 106314629 
               
               
                   
                 chr9 
                 106534209 
                 106534400 
               
               
                   
                 chr9 
                 108047150 
                 108047903 
               
               
                   
                 chr9 
                 108453798 
                 108454337 
               
               
                   
                 chr9 
                 110094621 
                 110095928 
               
               
                   
                 chr9 
                 110100907 
                 110102298 
               
               
                   
                 chr9 
                 114690009 
                 114691953 
               
               
                   
                 chr9 
                 21385742 
                 21386110 
               
               
                   
                 chr9 
                 36584091 
                 36585669 
               
               
                   
                 chr9 
                 44627976 
                 44630076 
               
               
                   
                 chr9 
                 45183701 
                 45184379 
               
               
                   
                 chr9 
                 64820556 
                 64821893 
               
               
                   
                 chr9 
                 66150149 
                 66150724 
               
               
                   
                 chr9 
                 69092444 
                 69093502 
               
               
                   
                 chr9 
                 83050145 
                 83051215 
               
               
                   
                 chr9 
                 95362984 
                 95365053 
               
               
                   
                 chr9 
                 99241977 
                 99242273 
               
               
                   
                 chr9 
                 99242400 
                 99245369 
               
               
                   
                 chrX 
                 147681816 
                 147682532 
               
               
                   
                 chr10 
                 28888088 
                 28888716 
               
               
                   
                 chr10 
                 53437662 
                 53438762 
               
               
                   
                 chr10 
                 80900473 
                 80901327 
               
               
                   
                 chr1 
                 108000968 
                 108002063 
               
               
                   
                 chr11 
                 102212266 
                 102212933 
               
               
                   
                 chr11 
                 109235707 
                 109237233 
               
               
                   
                 chr11 
                 22662409 
                 22662984 
               
               
                   
                 chr11 
                 3811935 
                 3812546 
               
               
                   
                 chr11 
                 53612110 
                 53613003 
               
               
                   
                 chr1 
                 158417149 
                 158418321 
               
               
                   
                 chr11 
                 58765982 
                 58766738 
               
               
                   
                 chr1 
                 162979533 
                 162980205 
               
               
                   
                 chr1 
                 166291190 
                 166292146 
               
               
                   
                 chr11 
                 69841848 
                 69842984 
               
               
                   
                 chr11 
                 70847302 
                 70848750 
               
               
                   
                 chr11 
                 83464295 
                 83464906 
               
               
                   
                 chr1 
                 186430240 
                 186431931 
               
               
                   
                 chr1 
                 186697939 
                 186699731 
               
               
                   
                 chr1 
                 187102071 
                 187102469 
               
               
                   
                 chr11 
                 94938664 
                 94939659 
               
               
                   
                 chr11 
                 96105595 
                 96107038 
               
               
                   
                 chr11 
                 96133733 
                 96134386 
               
               
                   
                 chr11 
                 96143071 
                 96143511 
               
               
                   
                 chr11 
                 97613914 
                 97614906 
               
               
                   
                 chr11 
                 98587132 
                 98589159 
               
               
                   
                 chr12 
                 111186780 
                 111187702 
               
               
                   
                 chr12 
                 30241655 
                 30242545 
               
               
                   
                 chr12 
                 45197481 
                 45198904 
               
               
                   
                 chr12 
                 53621042 
                 53623212 
               
               
                   
                 chr12 
                 55778410 
                 55779555 
               
               
                   
                 chr12 
                 70827419 
                 70827994 
               
               
                   
                 chr12 
                 71263656 
                 71264541 
               
               
                   
                 chr12 
                 73151554 
                 73155106 
               
               
                   
                 chr12 
                 83257544 
                 83259284 
               
               
                   
                 chr12 
                 99300922 
                 99301392 
               
               
                   
                 chr13 
                 21513212 
                 21513649 
               
               
                   
                 chr13 
                 35745963 
                 35748082 
               
               
                   
                 chr13 
                 49157646 
                 49158525 
               
               
                   
                 chr13 
                 52540971 
                 52542658 
               
               
                   
                 chr13 
                 55477782 
                 55479254 
               
               
                   
                 chr13 
                 58353808 
                 58354380 
               
               
                   
                 chr13 
                 58818728 
                 58820212 
               
               
                   
                 chr14 
                 104219050 
                 104219694 
               
               
                   
                 chr1 
                 41549409 
                 41549774 
               
               
                   
                 chr14 
                 19166845 
                 19167417 
               
               
                   
                 chr14 
                 30097112 
                 30098248 
               
               
                   
                 chr14 
                 51166853 
                 51167672 
               
               
                   
                 chr14 
                 53733790 
                 53734791 
               
               
                   
                 chr14 
                 53865226 
                 53866395 
               
               
                   
                 chr14 
                 54043521 
                 54045602 
               
               
                   
                 chr14 
                 63546684 
                 63549154 
               
               
                   
                 chr14 
                 64214773 
                 64215754 
               
               
                   
                 chr14 
                 65819186 
                 65820690 
               
               
                   
                 chr14 
                 7008650 
                 7010062 
               
               
                   
                 chr15 
                 100321886 
                 100322856 
               
               
                   
                 chr15 
                 27417132 
                 27417674 
               
               
                   
                 chr15 
                 27968069 
                 27968486 
               
               
                   
                 chr15 
                 37079209 
                 37080133 
               
               
                   
                 chr15 
                 39490076 
                 39490510 
               
               
                   
                 chr1 
                 55352211 
                 55352609 
               
               
                   
                 chr15 
                 68759313 
                 68760932 
               
               
                   
                 chr15 
                 79919013 
                 79919906 
               
               
                   
                 chr15 
                 85508940 
                 85509726 
               
               
                   
                 chr15 
                 97252471 
                 97253256 
               
               
                   
                 chr16 
                 42108443 
                 42109435 
               
               
                   
                 chr16 
                 57391719 
                 57392402 
               
               
                   
                 chr16 
                 58352052 
                 58352837 
               
               
                   
                 chr1 
                 66402075 
                 66402928 
               
               
                   
                 chr16 
                 81084948 
                 81085859 
               
               
                   
                 chr16 
                 85051940 
                 85055848 
               
               
                   
                 chr17 
                 34443844 
                 34444281 
               
               
                   
                 chr17 
                 5451100 
                 5452848 
               
               
                   
                 chr1 
                 77394488 
                 77395317 
               
               
                   
                 chr18 
                 25868426 
                 25868929 
               
               
                   
                 chr18 
                 32701107 
                 32702376 
               
               
                   
                 chr18 
                 34988219 
                 34989670 
               
               
                   
                 chr18 
                 37945468 
                 37947408 
               
               
                   
                 chr18 
                 60745072 
                 60745914 
               
               
                   
                 chr18 
                 61044585 
                 61044998 
               
               
                   
                 chr18 
                 69685663 
                 69686202 
               
               
                   
                 chr1 
                 91765466 
                 91766315 
               
               
                   
                 chr19 
                 43658075 
                 43659637 
               
               
                   
                 chr19 
                 5117032 
                 5117184 
               
               
                   
                 chr19 
                 55802945 
                 55803713 
               
               
                   
                 chr19 
                 58130598 
                 58131158 
               
               
                   
                 chr2 
                 113628540 
                 113629780 
               
               
                   
                 chr2 
                 148368993 
                 148369534 
               
               
                   
                 chr2 
                 148369553 
                 148369951 
               
               
                   
                 chr2 
                 179955743 
                 179957821 
               
               
                   
                 chr2 
                 92232293 
                 92234278 
               
               
                   
                 chr2 
                 93621635 
                 93622925 
               
               
                   
                 chr3 
                 127151720 
                 127152764 
               
               
                   
                 chr3 
                 135374094 
                 135375194 
               
               
                   
                 chr3 
                 136611345 
                 136612055 
               
               
                   
                 chr3 
                 138741405 
                 138741737 
               
               
                   
                 chr3 
                 144130403 
                 144131566 
               
               
                   
                 chr3 
                 28784766 
                 28785098 
               
               
                   
                 chr3 
                 87004578 
                 87005465 
               
               
                   
                 chr4 
                 114409124 
                 114411976 
               
               
                   
                 chr4 
                 125561505 
                 125562182 
               
               
                   
                 chr4 
                 133522280 
                 133523272 
               
               
                   
                 chr4 
                 135299619 
                 135300935 
               
               
                   
                 chr4 
                 148149542 
                 148150642 
               
               
                   
                 chr4 
                 154186710 
                 154188227 
               
               
                   
                 chr4 
                 41756406 
                 41756948 
               
               
                   
                 chr5 
                 113546929 
                 113547504 
               
               
                   
                 chr5 
                 116169864 
                 116171999 
               
               
                   
                 chr5 
                 143070791 
                 143071297 
               
               
                   
                 chr5 
                 52679340 
                 52680512 
               
               
                   
                 chr6 
                 119284067 
                 119284606 
               
               
                   
                 chr6 
                 145003894 
                 145005549 
               
               
                   
                 chr6 
                 147219194 
                 147220132 
               
               
                   
                 chr6 
                 52105770 
                 52106804 
               
               
                   
                 chr6 
                 52109489 
                 52110473 
               
               
                   
                 chr6 
                 52118616 
                 52120690 
               
               
                   
                 chr6 
                 52130359 
                 52133065 
               
               
                   
                 chr6 
                 52134341 
                 52135335 
               
               
                   
                 chr6 
                 55608676 
                 55609444 
               
               
                   
                 chr6 
                 88170526 
                 88171206 
               
               
                   
                 chr6 
                 88839352 
                 88840134 
               
               
                   
                 chr7 
                 121496679 
                 121497518 
               
               
                   
                 chr7 
                 130484240 
                 130486315 
               
               
                   
                 chr7 
                 18081786 
                 18082427 
               
               
                   
                 chr7 
                 26968690 
                 26971209 
               
               
                   
                 chr7 
                 44735606 
                 44736776 
               
               
                   
                 chr7 
                 44919263 
                 44920252 
               
               
                   
                 chr7 
                 45652130 
                 45653257 
               
               
                   
                 chr7 
                 62297270 
                 62297671 
               
               
                   
                 chr7 
                 79389605 
                 79390003 
               
               
                   
                 chr7 
                 96825159 
                 96825491 
               
               
                   
                 chr8 
                 108238955 
                 108239740 
               
               
                   
                 chr8 
                 111425321 
                 111427570 
               
               
                   
                 chr8 
                 112137124 
                 112138948 
               
               
                   
                 chr8 
                 112139103 
                 112141065 
               
               
                   
                 chr8 
                 122007273 
                 122007887 
               
               
                   
                 chr8 
                 124535330 
                 124537432 
               
               
                   
                 chr8 
                 124620001 
                 124620738 
               
               
                   
                 chr8 
                 127546771 
                 127548576 
               
               
                   
                 chr8 
                 14113008 
                 14113968 
               
               
                   
                 chr8 
                 60218064 
                 60218813 
               
               
                   
                 chr9 
                 106313871 
                 106314527 
               
               
                   
                 chr9 
                 108119711 
                 108121117 
               
               
                   
                 chr9 
                 108453798 
                 108454337 
               
               
                   
                 chr9 
                 21385742 
                 21386077 
               
               
                   
                 chr9 
                 45183767 
                 45185397 
               
               
                   
                 chr9 
                 66150221 
                 66150724 
               
               
                   
                 chr9 
                 72490554 
                 72492061 
               
               
                   
                 chr9 
                 83601188 
                 83601727 
               
               
                   
                 chr9 
                 89629425 
                 89629895 
               
               
                   
                 chr10 
                 126979364 
                 126980638 
               
               
                   
                 chr10 
                 127020412 
                 127022913 
               
               
                   
                 chr10 
                 127656943 
                 127658217 
               
               
                   
                 chr10 
                 41890728 
                 41891096 
               
               
                   
                 chr10 
                 80692225 
                 80693889 
               
               
                   
                 chr1 
                 108001004 
                 108001925 
               
               
                   
                 chr11 
                 103160706 
                 103161842 
               
               
                   
                 chr11 
                 109293793 
                 109294485 
               
               
                   
                 chr11 
                 115111730 
                 115113316 
               
               
                   
                 chr11 
                 120237470 
                 120237940 
               
               
                   
                 chr11 
                 120611069 
                 120611503 
               
               
                   
                 chr11 
                 120766874 
                 120767062 
               
               
                   
                 chr11 
                 22662409 
                 22662984 
               
               
                   
                 chr1 
                 135191990 
                 135192493 
               
               
                   
                 chr1 
                 139952104 
                 139952436 
               
               
                   
                 chr1 
                 163084626 
                 163084958 
               
               
                   
                 chr11 
                 69180232 
                 69180594 
               
               
                   
                 chr11 
                 69180685 
                 69181225 
               
               
                   
                 chr11 
                 78365131 
                 78365880 
               
               
                   
                 chr1 
                 193522768 
                 193523343 
               
               
                   
                 chr12 
                 113168003 
                 113169353 
               
               
                   
                 chr12 
                 118743027 
                 118744363 
               
               
                   
                 chr12 
                 31879325 
                 31880075 
               
               
                   
                 chr12 
                 58362526 
                 58363068 
               
               
                   
                 chr12 
                 60013490 
                 60014101 
               
               
                   
                 chr12 
                 71144570 
                 71145463 
               
               
                   
                 chr12 
                 84942362 
                 84943216 
               
               
                   
                 chr12 
                 86635810 
                 86637096 
               
               
                   
                 chr12 
                 87778503 
                 87779744 
               
               
                   
                 chr13 
                 40897757 
                 40899363 
               
               
                   
                 chr13 
                 52165707 
                 52166249 
               
               
                   
                 chr13 
                 52987856 
                 52990349 
               
               
                   
                 chr13 
                 92215958 
                 92216461 
               
               
                   
                 chr14 
                 120387491 
                 120388301 
               
               
                   
                 chr14 
                 46395955 
                 46396851 
               
               
                   
                 chr14 
                 50829932 
                 50832484 
               
               
                   
                 chr14 
                 50832626 
                 50833966 
               
               
                   
                 chr14 
                 56055810 
                 56057340 
               
               
                   
                 chr15 
                 102015649 
                 102016017 
               
               
                   
                 chr15 
                 10928320 
                 10928886 
               
               
                   
                 chr15 
                 37079176 
                 37080133 
               
               
                   
                 chr15 
                 76133841 
                 76134551 
               
               
                   
                 chr15 
                 78236579 
                 78237388 
               
               
                   
                 chr15 
                 85564542 
                 85565081 
               
               
                   
                 chr15 
                 88692381 
                 88692779 
               
               
                   
                 chr15 
                 89202174 
                 89205168 
               
               
                   
                 chr15 
                 89384916 
                 89385488 
               
               
                   
                 chr15 
                 97252471 
                 97253256 
               
               
                   
                 chr16 
                 24114972 
                 24115619 
               
               
                   
                 chr16 
                 57391719 
                 57392402 
               
               
                   
                 chr1 
                 66935142 
                 66935648 
               
               
                   
                 chr16 
                 84715521 
                 84716705 
               
               
                   
                 chr16 
                 92895397 
                 92895810 
               
               
                   
                 chr17 
                 12502580 
                 12503011 
               
               
                   
                 chr17 
                 24422788 
                 24423243 
               
               
                   
                 chr17 
                 28786279 
                 28786785 
               
               
                   
                 chr17 
                 45349645 
                 45350289 
               
               
                   
                 chr17 
                 80466736 
                 80468438 
               
               
                   
                 chr17 
                 84696258 
                 84698178 
               
               
                   
                 chr18 
                 36789687 
                 36790328 
               
               
                   
                 chr18 
                 60729268 
                 60731718 
               
               
                   
                 chr18 
                 60732259 
                 60732978 
               
               
                   
                 chr18 
                 65349251 
                 65349859 
               
               
                   
                 chr18 
                 70653550 
                 70654152 
               
               
                   
                 chr18 
                 75548120 
                 75548380 
               
               
                   
                 chr19 
                 25178692 
                 25179405 
               
               
                   
                 chr19 
                 29115205 
                 29115927 
               
               
                   
                 chr19 
                 34813837 
                 34814130 
               
               
                   
                 chr19 
                 34942556 
                 34943841 
               
               
                   
                 chr19 
                 37238481 
                 37239098 
               
               
                   
                 chr19 
                 37328982 
                 37330121 
               
               
                   
                 chr19 
                 43654651 
                 43655382 
               
               
                   
                 chr1 
                 94901325 
                 94902392 
               
               
                   
                 chr19 
                 54252753 
                 54254134 
               
               
                   
                 chr19 
                 5955777 
                 5957547 
               
               
                   
                 chr2 
                 163238827 
                 163239474 
               
               
                   
                 chr2 
                 30028984 
                 30029874 
               
               
                   
                 chr2 
                 58379608 
                 58380903 
               
               
                   
                 chr2 
                 58381061 
                 58381699 
               
               
                   
                 chr3 
                 121523021 
                 121523974 
               
               
                   
                 chr3 
                 121894506 
                 121894976 
               
               
                   
                 chr3 
                 83096129 
                 83096809 
               
               
                   
                 chr3 
                 83137592 
                 83139768 
               
               
                   
                 chr4 
                 105959139 
                 105959501 
               
               
                   
                 chr4 
                 105959592 
                 105960239 
               
               
                   
                 chr4 
                 135411138 
                 135412272 
               
               
                   
                 chr4 
                 138238949 
                 138239419 
               
               
                   
                 chr4 
                 140403814 
                 140404461 
               
               
                   
                 chr4 
                 148149575 
                 148150570 
               
               
                   
                 chr4 
                 148628253 
                 148628720 
               
               
                   
                 chr4 
                 149697690 
                 149698580 
               
               
                   
                 chr4 
                 150869421 
                 150870134 
               
               
                   
                 chr4 
                 35285775 
                 35286638 
               
               
                   
                 chr4 
                 40456117 
                 40456761 
               
               
                   
                 chr4 
                 59310821 
                 59311432 
               
               
                   
                 chr4 
                 97328719 
                 97329291 
               
               
                   
                 chr5 
                 113197288 
                 113198073 
               
               
                   
                 chr5 
                 113458495 
                 113459346 
               
               
                   
                 chr5 
                 116706401 
                 116708027 
               
               
                   
                 chr5 
                 118239146 
                 118240513 
               
               
                   
                 chr5 
                 123395820 
                 123396041 
               
               
                   
                 chr5 
                 124865500 
                 124866234 
               
               
                   
                 chr5 
                 65627192 
                 65629135 
               
               
                   
                 chr6 
                 119382061 
                 119382708 
               
               
                   
                 chr6 
                 124629874 
                 124631263 
               
               
                   
                 chr6 
                 31119916 
                 31120566 
               
               
                   
                 chr6 
                 85903153 
                 85903656 
               
               
                   
                 chr6 
                 88156373 
                 88156597 
               
               
                   
                 chr7 
                 127061589 
                 127063136 
               
               
                   
                 chr7 
                 132958148 
                 132959237 
               
               
                   
                 chr7 
                 140624014 
                 140624754 
               
               
                   
                 chr7 
                 140757459 
                 140757896 
               
               
                   
                 chr7 
                 15951594 
                 15952415 
               
               
                   
                 chr7 
                 29942884 
                 29943006 
               
               
                   
                 chr7 
                 30662992 
                 30664459 
               
               
                   
                 chr7 
                 49211159 
                 49211842 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                 Regions with Consistent Cancer-Specific Differential Methylation (C-DMRs) at a FDR of 5%. 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                 TSS 
                   
                   
               
               
                 chr 
                 start 
                 end 
                 deltaM 
                 fdr 
                 gene name 
                 relation 
                 distance 
                 CGI 
                 distToCGI 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 chr7 
                 153219537 
                 153220325 
                 −1.02674 
                 0.00000131 
                 DPP6 
                 inside 
                 1096601 
                 Far 
                 −2938 
               
               
                 chr21 
                 37858785 
                 37859555 
                 −1.08401 
                 0.00000164 
                 DYRK1A 
                 upstream 
                 49238 
                 Shore 
                 −369 
               
               
                 chr11 
                 117907224 
                 117907958 
                 1.00157 
                 0.00000328 
                 TMEM25 
                 inside 
                 3800 
                 Shore 
                 0 
               
               
                 chr19 
                 5159412 
                 5160095 
                 −1.02228 
                 0.00000628 
                 PTPRS 
                 inside 
                 131718 
                 Shore 
                 1469 
               
               
                 chr11 
                 65947037 
                 65948698 
                 −0.88203 
                 0.00000638 
                 NPAS4 
                 inside 
                 2054 
                 Shore 
                 −1064 
               
               
                 chr22 
                 35335058 
                 35337265 
                 −0.87143 
                 0.00000665 
                 CACNG2 
                 inside 
                 91583 
                 Far 
                 −44058 
               
               
                 chr19 
                 60702504 
                 60703541 
                 −0.94123 
                 0.00000892 
                 NAT14 
                 upstream 
                 11758 
                 Far 
                 3082 
               
               
                 chrX 
                 135941512 
                 135943110 
                 0.904877 
                 0.0000093 
                 GPR101 
                 promoter 
                 14 
                 Island 
                 0 
               
               
                 chr6 
                 52637426 
                 52638797 
                 −0.88756 
                 0.000013 
                 TMEM14A 
                 downstream 
                 20544 
                 Shore 
                 0 
               
               
                 chr7 
                 27106893 
                 27108203 
                 0.870706 
                 0.0000156 
                 HOXA2 
                 inside 
                 715 
                 Shore 
                 1503 
               
               
                 chr5 
                 1718233 
                 1720117 
                 −0.85903 
                 0.0000205 
                 MRPL36 
                 downstream 
                 132828 
                 Shore 
                 70 
               
               
                 chr19 
                 5297115 
                 5297780 
                 −0.93292 
                 0.0000226 
                 PTPRS 
                 upstream 
                 5302 
                 Far 
                 −5054 
               
               
                 chr2 
                 147061970 
                 147063253 
                 −0.86015 
                 0.0000229 
                 ACVR2A 
                 downstream 
                 1341608 
                 Shore 
                 −121 
               
               
                 chr8 
                 819298 
                 820365 
                 −0.87447 
                 0.0000243 
                 ERICH1 
                 upstream 
                 148073 
                 Shore 
                 1879 
               
               
                 chr22 
                 48414225 
                 48414719 
                 −0.96407 
                 0.0000249 
                 C22orf34 
                 inside 
                 22470 
                 Shore 
                 −1806 
               
               
                 chr13 
                 113615559 
                 113616275 
                 −0.91383 
                 0.000027 
                 FAM70B 
                 inside 
                 35597 
                 cover 
                 0 
               
               
                 chr15 
                 58474612 
                 58476390 
                 −0.81855 
                 0.0000399 
                 ANXA2 
                 inside 
                 1086 
                 Shore 
                 651 
               
               
                 chr7 
                 3984567 
                 3985861 
                 −0.84076 
                 0.0000663 
                 SDK1 
                 inside 
                 285898 
                 Far 
                 134310 
               
               
                 chr20 
                 33650044 
                 33650409 
                 0.946503 
                 0.0000695 
                 SPAG4 
                 downstream 
                 21969 
                 Shore 
                 1724 
               
               
                 chr13 
                 24843229 
                 24844069 
                 0.886019 
                 0.0000738 
                 ATP8A2 
                 downstream 
                 649349 
                 Shore 
                 0 
               
               
                 chr4 
                 62618513 
                 62619190 
                 −0.87267 
                 0.0000761 
                 LPHN3 
                 inside 
                 1571 
                 Far 
                 −552670 
               
               
                 chr3 
                 193607217 
                 193607552 
                 −0.93573 
                 0.0001116 
                 FGF12 
                 inside 
                 1153 
                 Shore 
                 960 
               
               
                 chr10 
                 5774977 
                 5775480 
                 0.88404 
                 0.00012066 
                 ASB13 
                 upstream 
                 26431 
                 Far 
                 −7274 
               
               
                 chr3 
                 82629728 
                 82630444 
                 −0.83773 
                 0.00014135 
                 GBE1 
                 upstream 
                 736294 
                 Far 
                 309227 
               
               
                 chr15 
                 70198455 
                 70199761 
                 −0.825 
                 0.00014832 
                 SENP8 
                 inside 
                 20595 
                 Shore 
                 −399 
               
               
                 chr8 
                 144543158 
                 144544971 
                 −0.7704 
                 0.00017229 
                 RHPN1 
                 upstream 
                 7196 
                 Far 
                 −9061 
               
               
                 chr19 
                 63146186 
                 63149398 
                 −0.7009 
                 0.00020946 
                 ZNF256 
                 inside 
                 1490 
                 Shore 
                 1100 
               
               
                 chr7 
                 27121979 
                 27122917 
                 0.793013 
                 0.00021477 
                 HOXA3 
                 inside 
                 2821 
                 Shore 
                 −28 
               
               
                 chr10 
                 129973472 
                 129974329 
                 −0.79104 
                 0.00024398 
                 MKI67 
                 upstream 
                 158828 
                 Far 
                 −19204 
               
               
                 chr5 
                 175019374 
                 175020470 
                 −0.78658 
                 0.00032057 
                 HRH2 
                 downstream 
                 23691 
                 Shore 
                 −1012 
               
               
                 chr15 
                 90735153 
                 90736013 
                 −0.77464 
                 0.0003365 
                 ST8SIA2 
                 downstream 
                 76946 
                 Shore 
                 1668 
               
               
                 chr20 
                 15408602 
                 15408931 
                 −0.87712 
                 0.00036397 
                 C20orf133 
                 inside 
                 572907 
                 Far 
                 1092905 
               
               
                 chr12 
                 128898887 
                 128900474 
                 −0.72032 
                 0.00038766 
                 TMEM132D 
                 inside 
                 53691 
                 Far 
                 5162 
               
               
                 chr20 
                 56858718 
                 56860982 
                 0.659681 
                 0.00039705 
                 GNAS 
                 inside 
                 58661 
                 cover 
                 0 
               
               
                 chr8 
                 118032349 
                 118033443 
                 −0.77052 
                 0.00039943 
                 LOC441376 
                 upstream 
                 7947 
                 Far 
                 −12209 
               
               
                 chr19 
                 55631492 
                 55632172 
                 −0.78998 
                 0.00040909 
                 MYBPC2 
                 inside 
                 29216 
                 Far 
                 −4003 
               
               
                 chr7 
                 27151538 
                 27154015 
                 0.661581 
                 0.00040909 
                 HOXA6 
                 covers 
                 0 
                 Shore 
                 0 
               
               
                 chr22 
                 36144969 
                 36145868 
                 0.759849 
                 0.00041153 
                 LRRC62 
                 upstream 
                 43445 
                 Shore 
                 0 
               
               
                 chr20 
                 16499527 
                 16500276 
                 −0.77576 
                 0.00043547 
                 C20orf23 
                 inside 
                 1801 
                 Shore 
                 1560 
               
               
                 chr7 
                 4865828 
                 4866751 
                 −0.75229 
                 0.00043806 
                 PAPOLB 
                 inside 
                 1399 
                 Shore 
                 1111 
               
               
                 chr8 
                 17060922 
                 17062917 
                 −0.68442 
                 0.0005137 
                 ZDHHC2 
                 inside 
                 61694 
                 Shore 
                 −1761 
               
               
                 chr12 
                 108883476 
                 108884015 
                 −0.79921 
                 0.00055912 
                 GIT2 
                 inside 
                 34467 
                 Far 
                 34165 
               
               
                 chr1 
                 14092469 
                 14093393 
                 0.743518 
                 0.00056075 
                 PRDM2 
                 upstream 
                 68308 
                 Shore 
                 −145 
               
               
                 chr9 
                 101171277 
                 101172098 
                 −0.75185 
                 0.00056896 
                 SEC61B 
                 upstream 
                 138557 
                 Far 
                 −72243 
               
               
                 chr7 
                 27129188 
                 27131713 
                 0.62826 
                 0.00063513 
                 HOXA3 
                 inside 
                 1450 
                 cover 
                 0 
               
               
                 chr9 
                 94987821 
                 94990808 
                 0.598843 
                 0.00069825 
                 WNK2 
                 inside 
                 131865 
                 Shore 
                 −165 
               
               
                 chr7 
                 145026589 
                 145027407 
                 −0.73801 
                 0.00073506 
                 CNTNAP2 
                 downstream 
                 2721611 
                 Far 
                 416556 
               
               
                 chr5 
                 16236219 
                 16237106 
                 −0.72798 
                 0.00074772 
                 FBXL7 
                 upstream 
                 243320 
                 Far 
                 −2799 
               
               
                 chr6 
                 168586102 
                 168588777 
                 0.621865 
                 0.00078025 
                 SMOC2 
                 inside 
                 221818 
                 Shore 
                 −153 
               
               
                 chr7 
                 27147025 
                 27148381 
                 0.688088 
                 0.00079587 
                 HOXA5 
                 overlaps 3′ 
                 1430 
                 Shore 
                 757 
               
               
                 chr6 
                 50873235 
                 50873811 
                 −0.77277 
                 0.00080038 
                 TFAP2B 
                 downstream 
                 45822 
                 Far 
                 21434 
               
               
                 chr9 
                 136758751 
                 136759638 
                 −0.72195 
                 0.000835 
                 COL5A1 
                 inside 
                 116868 
                 Far 
                 40696 
               
               
                 chr17 
                 74692733 
                 74693892 
                 −0.71657 
                 0.00085162 
                 LOC146713 
                 downstream 
                 237673 
                 Shore 
                 −909 
               
               
                 chr20 
                 44094989 
                 44097479 
                 −0.68354 
                 0.00086367 
                 SLC12A5 
                 inside 
                 24716 
                 Shore 
                 −634 
               
               
                 chr12 
                 128900559 
                 128905004 
                 −0.58154 
                 0.00089325 
                 TMEM132D 
                 inside 
                 49161 
                 Shore 
                 632 
               
               
                 chr9 
                 137437549 
                 137438193 
                 −0.74586 
                 0.00103239 
                 KIAA0649 
                 downstream 
                 82366 
                 Far 
                 6096 
               
               
                 chr8 
                 1032932 
                 1034329 
                 −0.68718 
                 0.00109097 
                 ERICH1 
                 upstream 
                 361707 
                 Shore 
                 1637 
               
               
                 chr20 
                 56841054 
                 56842229 
                 −0.67616 
                 0.00110609 
                 GNAS 
                 downstream 
                 77414 
                 Far 
                 5761 
               
               
                 chr11 
                 2190993 
                 2192468 
                 −0.65402 
                 0.00113066 
                 TH 
                 upstream 
                 41383 
                 Far 
                 −46172 
               
               
                 chr7 
                 80386676 
                 80389252 
                 −0.60191 
                 0.00118778 
                 SEMA3C 
                 promoter 
                 74 
                 Shore 
                 −14 
               
               
                 chr8 
                 846979 
                 849372 
                 −0.59665 
                 0.00119103 
                 ERICH1 
                 upstream 
                 175754 
                 Far 
                 −6574 
               
               
                 chr3 
                 191521264 
                 191521946 
                 −0.73631 
                 0.00122064 
                 CLDN1 
                 inside 
                 962 
                 Shore 
                 562 
               
               
                 chr3 
                 193338227 
                 193339771 
                 −0.67305 
                 0.00123738 
                 FGF12 
                 downstream 
                 268934 
                 Far 
                 268741 
               
               
                 chr16 
                 86201868 
                 86205260 
                 −0.67852 
                 0.00127148 
                 JPH3 
                 inside 
                 83999 
                 Shore 
                 327 
               
               
                 chr22 
                 48392638 
                 48393144 
                 −0.76072 
                 0.00128536 
                 C22orf34 
                 downstream 
                 44045 
                 Shore 
                 1818 
               
               
                 chr8 
                 966339 
                 968246 
                 −0.6265 
                 0.00129586 
                 ERICH1 
                 upstream 
                 295114 
                 Shore 
                 −581 
               
               
                 chr11 
                 73980533 
                 73981178 
                 −0.78485 
                 0.00133142 
                 POLD3 
                 downstream 
                 50234 
                 Shore 
                 0 
               
               
                 chr18 
                 32022373 
                 32023451 
                 −0.68242 
                 0.00135317 
                 MOCOS 
                 inside 
                 79230 
                 Shore 
                 −230 
               
               
                 chr18 
                 73809395 
                 73809862 
                 −0.76199 
                 0.00144347 
                 GALR1 
                 upstream 
                 698315 
                 Far 
                 9620 
               
               
                 chr13 
                 113548528 
                 113549312 
                 0.70947 
                 0.00145514 
                 GAS6 
                 inside 
                 41083 
                 Shore 
                 −393 
               
               
                 chr3 
                 129687744 
                 129688211 
                 0.759315 
                 0.00151474 
                 GATA2 
                 inside 
                 6506 
                 Shore 
                 0 
               
               
                 chr14 
                 95577239 
                 95578964 
                 −0.6455 
                 0.00151879 
                 C14orf132 
                 inside 
                 50921 
                 Shore 
                 −1084 
               
               
                 chr7 
                 92075312 
                 92075740 
                 −0.77713 
                 0.00152285 
                 CDK6 
                 inside 
                 225407 
                 Far 
                 −17503 
               
               
                 chr12 
                 16648850 
                 16649638 
                 0.700737 
                 0.00155156 
                 LMO3 
                 inside 
                 1059 
                 Far 
                 −693049 
               
               
                 chr19 
                 43436533 
                 43438474 
                 0.71493 
                 0.00159765 
                 PPP1R14A 
                 inside 
                 537 
                 Shore 
                 4 
               
               
                 chr7 
                 50436490 
                 50438081 
                 −0.63917 
                 0.00161044 
                 IKZF1 
                 overlaps 5′ 
                 0 
                 Shore 
                 −596 
               
               
                 chr13 
                 42886712 
                 42887185 
                 −0.75536 
                 0.00161901 
                 PIG38 
                 inside 
                 252469 
                 Far 
                 370673 
               
               
                 chr8 
                 100031420 
                 100033208 
                 0.611014 
                 0.00162763 
                 OSR2 
                 inside 
                 291 
                 Shore 
                 −806 
               
               
                 chr16 
                 31139986 
                 31140921 
                 −0.70124 
                 0.00167576 
                 TRIM72 
                 inside 
                 3089 
                 Far 
                 2105 
               
               
                 chr13 
                 87123702 
                 87125116 
                 0.642127 
                 0.00169358 
                 SLITRK5 
                 inside 
                 4752 
                 cover 
                 0 
               
               
                 chr2 
                 172826386 
                 172826961 
                 −0.72901 
                 0.00172973 
                 DLX2 
                 upstream 
                 150663 
                 Far 
                 −18042 
               
               
                 chr12 
                 88272781 
                 88274261 
                 −0.65038 
                 0.00193625 
                 DUSP6 
                 promoter 
                 2355 
                 Shore 
                 −506 
               
               
                 chr7 
                 50103520 
                 50103993 
                 −0.74337 
                 0.00198218 
                 ZPBP 
                 promoter 
                 149 
                 Shore 
                 −53 
               
               
                 chr7 
                 1182527 
                 1183550 
                 −0.70109 
                 0.00201859 
                 ZFAND2A 
                 upstream 
                 16204 
                 Far 
                 −15857 
               
               
                 chrX 
                 23042002 
                 23042541 
                 −0.75918 
                 0.00206093 
                 DDX53 
                 upstream 
                 111878 
                 Far 
                 217664 
               
               
                 chr8 
                 98356982 
                 98358151 
                 −0.64161 
                 0.00212045 
                 TSPYL5 
                 inside 
                 1200 
                 Shore 
                 629 
               
               
                 chr11 
                 132451645 
                 132454794 
                 −0.55186 
                 0.00212594 
                 OPCML 
                 inside 
                 452818 
                 Far 
                 2108 
               
               
                 chr4 
                 172202321 
                 172202941 
                 −0.71014 
                 0.00212594 
                 GALNT17 
                 downstream 
                 1996342 
                 Far 
                 767368 
               
               
                 chr11 
                 133791126 
                 133793856 
                 −0.56461 
                 0.00224415 
                 B3GAT1 
                 upstream 
                 4105 
                 Far 
                 −2997 
               
               
                 chr7 
                 129912706 
                 129913314 
                 −0.69892 
                 0.00255614 
                 MEST 
                 overlaps 3′ 
                 20050 
                 Shore 
                 0 
               
               
                 chr12 
                 38783104 
                 38784488 
                 0.607732 
                 0.00260186 
                 SLC2A13 
                 inside 
                 1439 
                 Shore 
                 741 
               
               
                 chr13 
                 112142200 
                 112143003 
                 −0.6783 
                 0.00268194 
                 C13orf28 
                 upstream 
                 5199 
                 Far 
                 11335 
               
               
                 chr7 
                 90064351 
                 90065026 
                 0.683928 
                 0.00268194 
                 PFTK1 
                 downstream 
                 612813 
                 Shore 
                 −51 
               
               
                 chr11 
                 103540808 
                 103541706 
                 −0.6721 
                 0.0027228 
                 PDGFD 
                 promoter 
                 572 
                 Shore 
                 −540 
               
               
                 chr21 
                 42057698 
                 42059424 
                 −0.5888 
                 0.00274344 
                 RIPK4 
                 inside 
                 893 
                 Shore 
                 0 
               
               
                 chr2 
                 4028568 
                 4028969 
                 −0.73928 
                 0.00285588 
                 ALLC 
                 upstream 
                 300436 
                 Island 
                 0 
               
               
                 chr11 
                 2243752 
                 2244711 
                 −0.64164 
                 0.00286305 
                 ASCL2 
                 downstream 
                 4046 
                 Shore 
                 1969 
               
               
                 chr5 
                 11954677 
                 11955633 
                 −0.64541 
                 0.00287742 
                 CTNND2 
                 inside 
                 1476 
                 Shore 
                 917 
               
               
                 chr5 
                 7900127 
                 7901165 
                 −0.66262 
                 0.00292092 
                 FASTKD3 
                 downstream 
                 20949 
                 Shore 
                 1780 
               
               
                 chr13 
                 109229281 
                 109231903 
                 −0.54967 
                 0.00303226 
                 IRS2 
                 inside 
                 5011 
                 Shore 
                 564 
               
               
                 chr13 
                 110126656 
                 110127336 
                 0.674417 
                 0.00312403 
                 FLJ12118 
                 inside 
                 29127 
                 Shore 
                 1831 
               
               
                 chr20 
                 48778557 
                 48780262 
                 −0.59546 
                 0.00331501 
                 PARD6B 
                 downstream 
                 23421 
                 Shore 
                 510 
               
               
                 chr14 
                 100997052 
                 100997806 
                 −0.66962 
                 0.00337263 
                 DIO3 
                 downstream 
                 101733 
                 Shore 
                 −1304 
               
               
                 chr3 
                 28591265 
                 28591843 
                 0.687621 
                 0.00340596 
                 ZCWPW2 
                 upstream 
                 49632 
                 Shore 
                 0 
               
               
                 chr11 
                 133445524 
                 133446466 
                 −0.65981 
                 0.0036033 
                 JAM3 
                 inside 
                 80392 
                 Shore 
                 −633 
               
               
                 chr5 
                 132392 
                 134453 
                 −0.57597 
                 0.00364751 
                 KIAA1909 
                 downstream 
                 108624 
                 Shore 
                 1975 
               
               
                 chrX 
                 142544143 
                 142544478 
                 −0.74381 
                 0.0037556 
                 SLITRK4 
                 inside 
                 6206 
                 Far 
                 4598 
               
               
                 chr20 
                 4928754 
                 4929383 
                 0.695671 
                 0.00377388 
                 SLC23A2 
                 inside 
                 761 
                 Far 
                 111977 
               
               
                 chr12 
                 112557273 
                 112558104 
                 −0.69254 
                 0.00396112 
                 LHX5 
                 upstream 
                 163014 
                 Far 
                 −43138 
               
               
                 chr16 
                 85092993 
                 85096638 
                 0.487544 
                 0.0039899 
                 FOXF1 
                 downstream 
                 8931 
                 Shore 
                 0 
               
               
                 chr10 
                 1437553 
                 1439129 
                 −0.58557 
                 0.00404802 
                 ADARB2 
                 inside 
                 330540 
                 Far 
                 −7539 
               
               
                 chr2 
                 242632887 
                 242634574 
                 −0.66358 
                 0.00405778 
                 FLJ33590 
                 upstream 
                 168241 
                 Shore 
                 1740 
               
               
                 chr2 
                 4028054 
                 4028513 
                 −0.72737 
                 0.00406756 
                 ALLC 
                 upstream 
                 299922 
                 Shore 
                 11 
               
               
                 chr19 
                 35406489 
                 35407329 
                 0.646091 
                 0.00410688 
                 ZNF536 
                 downstream 
                 333475 
                 Shore 
                 60 
               
               
                 chr7 
                 42233455 
                 42234204 
                 0.645604 
                 0.0041366 
                 GLI3 
                 upstream 
                 4036 
                 Shore 
                 0 
               
               
                 chr3 
                 174341049 
                 174341237 
                 −0.80111 
                 0.00415651 
                 SPATA16 
                 inside 
                 457 
                 Far 
                 254724 
               
               
                 chr5 
                 3586182 
                 3587073 
                 −0.70608 
                 0.00415651 
                 IRX1 
                 downstream 
                 67442 
                 Shore 
                 1557 
               
               
                 chr8 
                 22469866 
                 22470840 
                 −0.62573 
                 0.00420667 
                 SORBS3 
                 inside 
                 18110 
                 Far 
                 −4286 
               
               
                 chr6 
                 10501022 
                 10502013 
                 0.654216 
                 0.00428802 
                 TFAP2A 
                 downstream 
                 18579 
                 Shore 
                 −1938 
               
               
                 chr11 
                 31966319 
                 31967492 
                 −0.63749 
                 0.00433957 
                 RCN1 
                 downstream 
                 116160 
                 Shore 
                 −699 
               
               
                 chr1 
                 206062462 
                 206063805 
                 0.576185 
                 0.00447616 
                 LOC148696 
                 overlaps 5′ 
                 0 
                 Far 
                 44680 
               
               
                 chr22 
                 47267034 
                 47267870 
                 −0.63064 
                 0.00447616 
                 FAM19A5 
                 downstream 
                 265877 
                 Shore 
                 −1327 
               
               
                 chr6 
                 80711271 
                 80712497 
                 −0.59439 
                 0.00450821 
                 ELOVL4 
                 inside 
                 1443 
                 Shore 
                 966 
               
               
                 chr22 
                 47455137 
                 47456387 
                 −0.58401 
                 0.00455126 
                 FAM19A5 
                 inside 
                 77360 
                 Far 
                 −4801 
               
               
                 chr11 
                 134186796 
                 134187368 
                 −0.6669 
                 0.00469367 
                 B3GAT1 
                 upstream 
                 399775 
                 Far 
                 −48599 
               
               
                 chr19 
                 13474169 
                 13475470 
                 −0.62291 
                 0.00469367 
                 CACNA1A 
                 inside 
                 2846 
                 Far 
                 2282 
               
               
                 chr16 
                 25608094 
                 25609031 
                 −0.61772 
                 0.00474948 
                 HS3ST4 
                 downstream 
                 447477 
                 Shore 
                 1425 
               
               
                 chr8 
                 117611158 
                 117611838 
                 −0.64748 
                 0.00474948 
                 EIF3S3 
                 downstream 
                 225404 
                 Far 
                 225273 
               
               
                 chr20 
                 3603573 
                 3604604 
                 −0.59867 
                 0.00496688 
                 ADAM33 
                 inside 
                 6133 
                 Shore 
                 −800 
               
               
                 chr20 
                 59905352 
                 59906092 
                 −0.67681 
                 0.00503732 
                 CDH4 
                 inside 
                 39601 
                 Shore 
                 −1622 
               
               
                 chr14 
                 52326048 
                 52327382 
                 −0.59637 
                 0.00514462 
                 GNPNAT1 
                 inside 
                 750 
                 Shore 
                 32 
               
               
                 chr22 
                 46984389 
                 46985561 
                 −0.58562 
                 0.00514462 
                 LOC388915 
                 upstream 
                 66632 
                 Shore 
                 −218 
               
               
                 chr7 
                 152249022 
                 152250754 
                 −0.63648 
                 0.00515666 
                 ACTR3B 
                 upstream 
                 65627 
                 Far 
                 2095 
               
               
                 chr7 
                 27108458 
                 27111260 
                 0.508493 
                 0.00515666 
                 HOXA2 
                 overlaps 5′ 
                 0 
                 cover 
                 0 
               
               
                 chr5 
                 158465126 
                 158466712 
                 0.548688 
                 0.00532789 
                 EBF1 
                 upstream 
                 5780 
                 cover 
                 0 
               
               
                 chr7 
                 149667109 
                 149668386 
                 0.570024 
                 0.00536522 
                 RARRES2 
                 inside 
                 1252 
                 Shore 
                 6 
               
               
                 chr10 
                 3499370 
                 3500060 
                 −0.64479 
                 0.00540278 
                 PITRM1 
                 upstream 
                 294368 
                 Far 
                 −8794 
               
               
                 chr11 
                 31780765 
                 31782111 
                 0.582076 
                 0.00542795 
                 PAX6 
                 inside 
                 7322 
                 Shore 
                 208 
               
               
                 chr7 
                 139121471 
                 139122253 
                 0.621564 
                 0.00552964 
                 TBXAS1 
                 downstream 
                 244217 
                 Shore 
                 1622 
               
               
                 chr17 
                 14831980 
                 14832519 
                 −0.66274 
                 0.00555532 
                 FLJ45831 
                 upstream 
                 207736 
                 Far 
                 272136 
               
               
                 chr3 
                 148446946 
                 148448043 
                 −0.61085 
                 0.00563299 
                 ZIC4 
                 downstream 
                 159053 
                 Far 
                 111759 
               
               
                 chr18 
                 11140361 
                 11141025 
                 −0.64161 
                 0.00567218 
                 FAM38B 
                 upstream 
                 452548 
                 Shore 
                 −425 
               
               
                 chr19 
                 4505154 
                 4505834 
                 −0.63538 
                 0.00569843 
                 SEMA6B 
                 inside 
                 3668 
                 Shore 
                 1102 
               
               
                 chr4 
                 81341228 
                 81342411 
                 0.593058 
                 0.0057248 
                 PRDM8 
                 inside 
                 2092 
                 Shore 
                 121 
               
               
                 chr13 
                 100427954 
                 100428562 
                 −0.65947 
                 0.00583131 
                 VGCNL1 
                 downstream 
                 438251 
                 Far 
                 −302230 
               
               
                 chr1 
                 221053963 
                 221054618 
                 −0.65816 
                 0.00595319 
                 FLJ43505 
                 upstream 
                 63194 
                 Shore 
                 249 
               
               
                 chr9 
                 97304533 
                 97306772 
                 0.538529 
                 0.00598058 
                 PTCH1 
                 inside 
                 3879 
                 Shore 
                 1524 
               
               
                 chr10 
                 134597978 
                 134600218 
                 −0.58526 
                 0.00606339 
                 C10orf93 
                 inside 
                 5835 
                 Far 
                 5435 
               
               
                 chr10 
                 24025367 
                 24026498 
                 −0.60529 
                 0.00611915 
                 C10orf67 
                 upstream 
                 351590 
                 Shore 
                 −383 
               
               
                 chr19 
                 50669649 
                 50670313 
                 0.642613 
                 0.00611915 
                 FOSB 
                 overlaps 5′ 
                 0 
                 Shore 
                 −1547 
               
               
                 chr18 
                 491107 
                 491721 
                 0.648047 
                 0.006232 
                 COLEC12 
                 promoter 
                 423 
                 Shore 
                 −385 
               
               
                 chr17 
                 41333049 
                 41334735 
                 −0.54819 
                 0.00626049 
                 MAPT 
                 inside 
                 126808 
                 Far 
                 −2213 
               
               
                 chr12 
                 52430235 
                 52431320 
                 0.598153 
                 0.00636111 
                 CALCOCO1 
                 upstream 
                 22750 
                 Island 
                 0 
               
               
                 chr13 
                 67580738 
                 67581346 
                 −0.63959 
                 0.00640466 
                 PCDH9 
                 upstream 
                 878275 
                 Far 
                 875559 
               
               
                 chr5 
                 134553843 
                 134554689 
                 0.606657 
                 0.00641924 
                 H2AFY 
                 downstream 
                 208137 
                 Shore 
                 137 
               
               
                 chr12 
                 122813965 
                 122816002 
                 −0.551 
                 0.00652206 
                 ATP6V0A2 
                 upstream 
                 3575 
                 Shore 
                 −758 
               
               
                 chr20 
                 24399131 
                 24400197 
                 0.576626 
                 0.00652206 
                 C20orf39 
                 inside 
                 194969 
                 Island 
                 0 
               
               
                 chr2 
                 100303439 
                 100304155 
                 0.61944 
                 0.00664131 
                 LONRF2 
                 upstream 
                 11041 
                 Shore 
                 56 
               
               
                 chr13 
                 21140646 
                 21141533 
                 0.594077 
                 0.0067472 
                 FGF9 
                 downstream 
                 32650 
                 Shore 
                 0 
               
               
                 chr8 
                 132984463 
                 132985363 
                 −0.6234 
                 0.00679303 
                 KIAA0143 
                 downstream 
                 109587 
                 Shore 
                 141 
               
               
                 chr11 
                 1861791 
                 1862726 
                 −0.59254 
                 0.006901 
                 LSP1 
                 inside 
                 7341 
                 Shore 
                 −1881 
               
               
                 chr10 
                 101273278 
                 101274941 
                 0.562231 
                 0.00691655 
                 NKX2-3 
                 downstream 
                 11326 
                 Shore 
                 −348 
               
               
                 chr13 
                 113850844 
                 113851732 
                 0.592061 
                 0.00694773 
                 RASA3 
                 inside 
                 64464 
                 Far 
                 2436 
               
               
                 chr7 
                 32076356 
                 32076652 
                 0.715435 
                 0.00699473 
                 PDE1C 
                 inside 
                 863 
                 Shore 
                 0 
               
               
                 chr11 
                 45645190 
                 45645996 
                 −0.6053 
                 0.00701046 
                 CHST1 
                 promoter 
                 1443 
                 Shore 
                 −1119 
               
               
                 chr19 
                 16876450 
                 16876750 
                 −0.74637 
                 0.00701046 
                 CPAMD8 
                 inside 
                 121718 
                 Far 
                 −6593 
               
               
                 chr8 
                 53636408 
                 53637226 
                 −0.60042 
                 0.00702621 
                 UNQ9433 
                 inside 
                 3338 
                 Far 
                 2871 
               
               
                 chr15 
                 24571127 
                 24572559 
                 −0.55445 
                 0.00705782 
                 GABRB3 
                 promoter 
                 1108 
                 Shore 
                 −1091 
               
               
                 chr6 
                 133605067 
                 133606789 
                 0.529372 
                 0.00708955 
                 EYA4 
                 inside 
                 287568 
                 Shore 
                 0 
               
               
                 chr12 
                 88266873 
                 88268978 
                 −0.49621 
                 0.0072177 
                 DUSP6 
                 inside 
                 1448 
                 Shore 
                 321 
               
               
                 chr17 
                 782607 
                 784014 
                 −0.56251 
                 0.00723386 
                 NXN 
                 inside 
                 45745 
                 Far 
                 12943 
               
               
                 chr19 
                 36535076 
                 36535822 
                 0.607202 
                 0.00734784 
                 TSHZ3 
                 upstream 
                 73062 
                 Shore 
                 0 
               
               
                 chr13 
                 20184925 
                 20186542 
                 −0.53392 
                 0.00741367 
                 IL17D 
                 inside 
                 8693 
                 Far 
                 7069 
               
               
                 chr17 
                 22902924 
                 22903499 
                 −0.63407 
                 0.00763111 
                 KSR1 
                 inside 
                 71344 
                 Far 
                 53125 
               
               
                 chr1 
                 32992405 
                 32992989 
                 0.632486 
                 0.00780208 
                 KIAA1522 
                 inside 
                 20168 
                 Shore 
                 0 
               
               
                 chr15 
                 32835765 
                 32836849 
                 −0.56319 
                 0.00792371 
                 CX36 
                 promoter 
                 1785 
                 Shore 
                 −993 
               
               
                 chr12 
                 130718351 
                 130718755 
                 −0.68171 
                 0.00801157 
                 SFRS8 
                 downstream 
                 131479 
                 Far 
                 −5588 
               
               
                 chr13 
                 36392772 
                 36394298 
                 0.523296 
                 0.00801157 
                 ALG5 
                 downstream 
                 77178 
                 Shore 
                 −20 
               
               
                 chr20 
                 61186047 
                 61186916 
                 −0.58658 
                 0.00801157 
                 BHLHB4 
                 upstream 
                 77261 
                 Shore 
                 1296 
               
               
                 chr11 
                 19323912 
                 19324590 
                 0.644909 
                 0.00802925 
                 E2F8 
                 upstream 
                 104830 
                 inside 
                 0 
               
               
                 chr12 
                 111302662 
                 111303588 
                 0.576207 
                 0.00820783 
                 RPL6 
                 downstream 
                 28237 
                 Island 
                 0 
               
               
                 chr15 
                 97011564 
                 97012941 
                 0.531506 
                 0.0082802 
                 IGF1R 
                 inside 
                 306092 
                 Shore 
                 0 
               
               
                 chr16 
                 49141667 
                 49142498 
                 −0.59792 
                 0.00837144 
                 NKD1 
                 inside 
                 83643 
                 Shore 
                 −701 
               
               
                 chr14 
                 57669356 
                 57669957 
                 −0.63311 
                 0.00853784 
                 C14orf37 
                 inside 
                 18642 
                 Far 
                 18087 
               
               
                 chr8 
                 144372893 
                 144373912 
                 −0.59142 
                 0.0085565 
                 LOC338328 
                 promoter 
                 2476 
                 Far 
                 9171 
               
               
                 chr9 
                 124022303 
                 124023189 
                 0.590922 
                 0.00861269 
                 LHX6 
                 inside 
                 7615 
                 Shore 
                 0 
               
               
                 chr19 
                 3240846 
                 3241458 
                 −0.61842 
                 0.0086692 
                 BRUNOL5 
                 inside 
                 6612 
                 Far 
                 2809 
               
               
                 chr16 
                 4101996 
                 4102769 
                 0.594061 
                 0.00884063 
                 ADCY9 
                 inside 
                 3417 
                 Far 
                 2040 
               
               
                 chr12 
                 4889938 
                 4890628 
                 0.61045 
                 0.00889841 
                 KCNA1 
                 close to 3′ 
                 1662 
                 inside 
                 0 
               
               
                 chr3 
                 151719593 
                 151721472 
                 −0.52881 
                 0.00895651 
                 SERP1 
                 downstream 
                 25645 
                 Far 
                 24824 
               
               
                 chr19 
                 41058856 
                 41059386 
                 −0.6366 
                 0.00903448 
                 APLP1 
                 inside 
                 3151 
                 Shore 
                 −1192 
               
               
                 chr7 
                 71437052 
                 71438143 
                 −0.55387 
                 0.00903448 
                 CALN1 
                 inside 
                 1752 
                 Shore 
                 550 
               
               
                 chr9 
                 37023001 
                 37023958 
                 0.572428 
                 0.00919216 
                 PAX5 
                 inside 
                 517 
                 Shore 
                 177 
               
               
                 chr20 
                 33336228 
                 33337040 
                 −0.58612 
                 0.00921203 
                 FAM83C 
                 overlaps 3′ 
                 6598 
                 Shore 
                 −75 
               
               
                 chr7 
                 5360426 
                 5361424 
                 0.575878 
                 0.00931195 
                 SLC29A4 
                 upstream 
                 50199 
                 Shore 
                 974 
               
               
                 chr18 
                 75366596 
                 75367142 
                 −0.77008 
                 0.00935217 
                 NFATC1 
                 inside 
                 23167 
                 Far 
                 4639 
               
               
                 chr6 
                 7413675 
                 7414250 
                 −0.61922 
                 0.00939254 
                 RIOK1 
                 upstream 
                 50409 
                 Far 
                 72267 
               
               
                 chr11 
                 64244495 
                 64245421 
                 −0.57059 
                 0.00943306 
                 NRXN2 
                 inside 
                 1814 
                 Shore 
                 1648 
               
               
                 chr16 
                 7291114 
                 7292175 
                 −0.5578 
                 0.00949411 
                 A2BP1 
                 inside 
                 408671 
                 Far 
                 2159 
               
               
                 chr8 
                 3257254 
                 3257862 
                 −0.61199 
                 0.00949411 
                 CSMD1 
                 inside 
                 1581873 
                 Far 
                 −389899 
               
               
                 chr5 
                 88221043 
                 88221995 
                 0.573951 
                 0.00955551 
                 MEF2C 
                 upstream 
                 6264 
                 Island 
                 0 
               
               
                 chr13 
                 99440030 
                 99441015 
                 0.573722 
                 0.00959662 
                 ZIC2 
                 upstream 
                 3012 
                 Shore 
                 0 
               
               
                 chr10 
                 102811316 
                 102812341 
                 −0.55274 
                 0.00965857 
                 KAZALD1 
                 overlaps 3′ 
                 2996 
                 inside 
                 0 
               
               
                 chr17 
                 71291527 
                 71292204 
                 −0.59686 
                 0.00988864 
                 H3F3B 
                 upstream 
                 4073 
                 Shore 
                 237 
               
               
                 chr10 
                 112248574 
                 112249464 
                 0.566331 
                 0.00999474 
                 DUSP5 
                 inside 
                 11825 
                 Shore 
                 0 
               
               
                   
               
               
                 DeltaM is cancer minus normal. 
               
               
                 FDR is false discovery rate. 
               
               
                 Columns are chromosome, start, end, delta M, fdr, gene, relation to gene, distance to TSS, relation to CGI, distance to CGI