dataesr/scientific-paragraphs-categorization huggingface dataset:
O8 International biobanking in the era of precision medicine Jim Vaught President, ISBER, Editor-in-Chief, Biopreservation & Biobanking, USA BMC Genomics 2016, 17(Suppl 6):O8 Biospecimens are collected from patients and other donors in a variety of ways for basic, clinical and epidemiologic research studies. Methods for collecting, processing, storing and analyzing biospecimens have usually been developed locally for diagnostic and research purposes, with little consideration for standardization or long-term quality management. Biospecimen management has developed into a more scientifically-based endeavor, as researchers have realized that biospecimens and data of consistent quality are required as we enter the era of precision medicine. Best practices have been developed by organizations such as the International Society for Biological and Environmental and Repositories (ISBER), the U.
With advances in molecular biology (i. e. , OMICs) and computational capabilities, society is on the verge of demystifying the causes of diseases with an expectation of better diagnostics, prognostics, and possible therapeutics for health and well-being. However, forensic science (for 30 years) embraced the field of genetics and built an entire infrastructure relying on DNA typing from biospecimen collection to final results integrated under strict and formal quality assurance guidelines. Both the medical and forensic disciplines rely on the accumulation of big data to perform precision, or personalized, analyses. These two disciplines have built biobanks and/or databanks with different rationales, designs and governance. Databanks and databases can be exploited to harness the power of emerging technologies and either enable detection of putative genes or potential suspects, and promote development of innovative biomarkers and treatments.
Both resources must provide value, have proper ethical/conduct governance, develop capabilities to store and retrieve samples and annotated data, and be managed and maintained. Medical databases typically are governed by institutions (often not government agencies, although constrained by laws) and can be either free to those who donate samples or consumers pay for tests. Samples and metadata are provided on a voluntary consent basis, and the resource may be available to many interested parties. Forensic databases are controlled by the government, access is limited to law enforcement, and sample donation often is mandatory. Medical and forensic big data resources, views of data sharing, experiences of both systems users are discussed. Another resource, the human microbiome, should be considered.
O14 From association to causality: translation of GWAS findings for genomic medicine Ahmed Rebai Laboratory of Molecular and Cellular Screening Processes (Bioinformatics Group), Centre of Biotechnology of Sfax, P. O. Box "1177", Sfax, Tunisia BMC Genomics 2016, 17(Suppl 6):O14 With the decrease of the cost of high throughput genotyping and sequencing, Genome wide Association Studies (GWAS) have become a good approach to identify sequence variations and mainly Single nucleotide polymorphisms (SNP) that are related to complex and common diseases. However, GWAS data allow only associational inference and is only able to identify sequence variants that are statistically associated with the disease status. The last seven years have seen an exponential growth in the number of GWAS which resulted in over 15 thousand associated Single Nucleotide polymorphisms (SNPs) identified in more than 2100 published studies.
Here I build on recent works within the Bayesian networks modeling framework, to present an original approach to test causality based on observation data only. Based on standard GWAS data alone, this approach provides a measure for ranking causal effects of associated variants. The accuracy and stability of this measure is assessed and compared to other approaches. Selecting the most likely causal variants from GWAS results will allow the prioritization and designs of targeted experiments to unravel causal mechanisms underlying association and effective clinical translation of GWAS findings for genomic medicine, including individual risk prediction, advanced clinical strategies and personalized treatments. Genome-wide association study data is used widely to identify the genetic variants associated with complex traits or common disease.
Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP) is a refined database, containing ∼ 8. 87 million SNP associations reported in 2044 studies and ~178 thousand phenotypes, derived from GWAS data. GRASP v2. 0 users face difficulties in access and correlation of SNPs with traits. Thus we aimed to design an interactive database providing detailed information of SNPs required for better data interpretation, communication between possible collaborators and new hypotheses to be generated. To develop a web application, we used ASP. net as front-end tool; SQL server, MatLab, D3. js, D3Plus. js and jQuery data table as back-end tools; JavaScript and Ajax for client-side purpose. MATLAB was used to analyse the statistical replication and evolutionary information of each SNPs and all SNPs were mapped to genome position of human genome build 38 (hg38) using LiftOver.
We developed a new web application called E-GRASP using an advance tool and different filter code to retrieve and represent data in better way leading to fast and easy data analysis. We retrieved and retained all information of GRASP in E-GRASP and added new information including statistical replication and evolutionary information of each SNPs. E-GRASP provides information under following categories: (i) SNPs view-provides information about SNPid, PMID, P-value, chromosome, position, number of studies and phenotypes for each SNPs; (ii) Study view-explains about unique SNPs replication in each studies and phenotypes, and (iii) Evolutionary view-describes evolutionary information including E-value for SNP phenotype association, E-rank of the evolutionary rate and time span of the position retrieved from the "E-rank Web Server" for each SNP.
Results Our interactome analysis combined experimental and predicted PPIs  [2, 3]. PPIs that were coming from different databases showed a small overlap, and also male infertility proteins are not well known and knowledge of their interactors are based on low throughput studies. Only 26 proteins were found to be annotated in the ReactomeDB  [4]. Our curated network representing Antioxidant Response pathway proteins and their interactors consists of 101 nodes and 235 edges. Conclusions Almost 40 % of human genes do not have a PfamA or GO annotation, no current studies provide a list of potential functions  [3, 4]. We found that only two proteins, superoxide dismutase 1 and 2 (SOD1 and SOD2) had genetic interactions, while SOD3 had only one physical interaction which was inferred from mouse, also nitric oxidase 4 (NOX4) and glutathione peroxidase 5 (GPX5) didn't show any interactions Other proteins showed physical interactions and more than 90 % those proteins had minimum 4 unique interactors.
Materials and methods To identity genes that co-operate with Ptch1 in MB development, we have performed a Sleeping Beauty insertional mutagenesis screen in this murine model. To identify the genes responsible for this enhanced tumour formation we have used Splinkerette-PCR and 454-FLX sequencing to define SB insertion sites within 40 tumours. Monte Carlo and Kernel Convolution statistical methods were applied on these data to identify statistically significant candidate MB genes defined by common insertion sites (CISs). Sophisticated bioinformatic analysis were conducted in human gene expression datasets to identify a plausible neuronal network. Illumina beads microarray was carried out on mutagenised mice primary tumour samples.
P32 An integrated database of GWAS SNVs and their evolutionary properties Heba Abusamra 1 , Sajjad Karim 1 , Hend F Nour eldin 1 , Elham M Alhathli 1 , Nada Salem 1 , Sudhir Kumar Background Genome-wide repository of associations between SNPs and phenotypes (GRASP) is a centralized repository of publically available genome-wide association study (GWAS) results. GRASP v2. 0 contains ∼ 8. 87 million SNP associations reported in 2044 studies and ~178 thousand phenotypes  [1]. However, this database does not contain evolutionary information about individual SNVs, particularly the prioritization of SNVs by using evolutionary conservation of SNVs.
P37 E-GRASP: Adding an evolutionary component to the genome-wide repository of associations (GRASP) resource Hend F Nour Eldin 1 , Sajjad Karim Background Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP) is an extensive database of publicly available genomewide association study (GWAS) results, which are the genetic variants (single nucleotide variants, SNVs) associated with complex traits and diseases  [1]. This resource is primarily a population genetics resource, which currently ignores the evolutionary information available for the positions harboring SNVs. We have developed a web application to make the information available in the GRASP2 resource along with the evolutionary information.
Results We developed a new web application and database named "E-GRASP" to enable easy and fast data retrieval of SNVs in GRASP and associated evolutionary information. E-GRASP presents three different views. (a) SNV View that contains information about each SNV such as SNPid, PMID, P value, chromosome number, position, number of studies reporting the SNV, and number of phenotypes associated with each SNV. (b) Study View that presents information on individual studies and basic information, including PMID, list of SNVs, their replication, phenotypes. (c) Evolutionary View that contains evolutionary conservation information as well as the E-rank  [2]  of SNVs in individual studies (plus P value, E value, P-rank, E-rank, and MAF) (Fig. 13 ). Conclusions E-GRASP will enable users to examine the GWAS data along with evolutionary information.
Materials and methods This prospective proteomic study analyzed proteins in spermatozoa from infertile men. Briefly, spermatozoa from infertile patients (n = 5) were fractionated on density gradient (80, 60 and 40 %) layers. Fraction 1 (F1) refers to the least mature stage having lowest density whereas the fraction 4 (F4) comprises of the most dense and morphologically mature motile spermatozoa. Fraction 2 (F2) and fraction 3 (F3) are the intermediate stages. Proteins were extracted and separated by 1-D gel. Bands were digested with trypsin and analyzed on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Protein identification was done using Mascot, SEQUEST and X! Tandem which were set up to search the human reference with database assuming trypsin as the digestion enzyme. Functional analyses of proteins were performed using gene ontology analyses.
P48 An evolutionary re-assessment of GWAS single nucleotide variants implicated in the Cholesterol traits Elham M Alhathli 1 , Sajjad Karim Background A number of loci associated with total cholesterol concentration and cardiovascular diseases are identified by genome-wide association studies (GWAS). The Genome-Wide Repository of association between SNPs and phenotype (GRASP v2. 0) database has most of the publically available data for diverse phenotypes including total cholesterol  [1]. These direct association results do not account for difference in evolutionary conservation of positions and the power of the test, which may not identify all SNPs with significant associations  [2]. We applied the E-ranking approach, based on P value, allele frequency, and evolutionary conservation score, on total cholesterol data in GRASP to reassess the significant and reproducible genetic disease associations  [2].
Conclusions Evolutionary ranking of genomic positions to filter disease associated SNPs can improve the reproducibility of SNPs at faster evolving sites and can enhance SNP discovery in published GWAS. These results are based on replication in studies with a limited number of significant SNPs, therefore, using full dataset can contribute significantly for improvement of the discovery of genetic variants in future work. Background Adult cartilage has limited intrinsic self-repair capacity and poor regeneration. New hope come from using stem cells for cartilage tissue engineering  [1]. Mesenchymal stem cells especially those from the Wharton's Jelly of the human umbilical cord (hWJSCs) represent an attractive source for chondrogenic differentiation, given their capacity for self-renewal, ease of access and lack of immunogenic or tumorigenic activities  [2].
Materials and methods An in silico approach based on well-established computational methods in quantitative structure-activity relationship, pharmacophore identification and computational docking software named CLC drug discovery Workbench were used  [6]. Protein Data Bank was used to download the protein structure of FTO (3LFM). Selected natural compounds known to suppress the FTO action involved in obesity and lipid metabolism such as (a)Luteolin (Reseda luteola),(b)Quercetin(Emblica officinalis),(c) Capsaicin(Capsicum),(d)Abscisic acid(Abscisin II), (e)Ajoene(Allium sativum), and(f) Diosgenin(Dioscorea villosa) were subjected to comparative docking analysis. Subsequent in vitro validation of the selected compounds using cell culture will be envisioned.
Materials and methods Two different in silico approaches were used; the first (forward) started from a list of genes which expression is changed during aging, that are available in the GenAge database (http://genomics. senescence. info/genes/) or described in the literature as having their expression affected by telomere shortening. These genes were then filtered based on their proximity to telomere, their involvement in age-related diseases, and other attributes (gene size, signaling and regulation pathways, expression profile, etc. ) using a weighted score. A set of 24 genes (with a standardized cut-off score of 0. 5) was identified as genes of high interest for further experimental validation. The second (backward) approach consisted of a genome scan of all the genes located within 10 Mb from telomere using a machine-learning based procedure (Bayesian networks).
Results Preliminary results showed modest sensitivity of the approach, which is expected given the reduced size of the training dataset and the nonavailability of well characterized distinctive features of this class of genes and a deep understanding of TPE-OLD mechanisms. In fact, the main challenge in the backward approach is to define a training set with 'positive' and 'negative' genes, that is large enough to ensure high precision of the model learning process. The second challenge in this approach is choosing the gene features that are relevant and highly predictive of the TPE-OLD regulation status.
Materials and methods We have obtained Affymetrix Microarray CEL files from Gene Expression Omnibus (GEO) (GSE49515). The CEL files were then analyzed using Genespring™ GX 13. 1 software (Agilent, USA). Statistical analysis was done using unpaired Student's t-test to obtain differentially expressed genes (P < 0. 05) with 2-fold cut-off between normal liver tissue and HCC samples. The differentially expressed genes were then subjected to Hierarchical Clustering to obtain HCC specific gene clusters. Furthermore, we have used Ingenuity Pathway Analysis (IPA) software (Ingenuity Systems, USA) to obtain differentially expressed canonical pathways and novel gene networks in HCC.
Materials and methods We present two affected male children from a consanguineous family having developmental delay and seizures. We performed exome sequencing on one of the siblings and both parents on the Illumina HiSeq 2500. Base calling was performed using CASAVA v1. 8. 2 and reads were mapped to the hg19 reference sequence using the BWAbacktrack algorithm from BWA v0. 5. 9. Variant calling was performed using GATK 1. 1-28. Variants were classified into loss of functions and missense. The rare variants were defined as those at < 5 % frequency in 1000 Genomes, NHBLI Exome Sequencing Project, Exome Aggregation Consortium and one in-house databases.
Materials and methods High throughput data, obtained from individual patients, using advanced technological platforms such as microarrays, next generation sequencing (NGS) methodologies were examined using freewares like R and commercial platforms like Genespring GX13. 1 (Agilent, USA), Partek Genomics Suite (Partek Inc. , USA), JMP Genomics Software (SAS, USA) etc. , The differential expression patterns of immune genes has been analysed using the Database for Annotation and Visualization and Integrated Discovery (DAVID), and commercial knowledge bases like Pathway Analysis (IPA) (Ingenuity Systems, Qiagen USA), Pathway Studio (Elsevier, Netherlands) etc. , to decipher biomarkers and novel immune-regulatory pathways.
The NCCs (211 detected) were more prevalent than PCC (162). PCC-containing proteins are significantly longer than those having NCCs (p = 2. 10 16 ). The most prevalent virus families having PCC and NCC were Herpesviridae followed by Papillomaviridae. However, the single-strand RNA group has on average three times more NCC than PCC. According to the functional domain classification, a significant difference in distribution was observed between PCC and NCC (p = 2. 10 -8 ) with the occurrence of NCCs being more frequent in C-terminal region while PCC more often fall within functional domains. Only 29 proteins sequences contained both NCC and PCC. Moreover, 101 NCC were conserved in 84 proteins while only 62 PCC were conserved in 60 protein sequences. To understand the mechanism by which the membrane translocation functionalities are embedded in viral proteins, we screened our PCC for sequences corresponding to cell-penetrating peptides (CPPs) using two online databases: CellPPd and CPPpred.
Materials and methods Proteins selected for the present study are VP35 glycoprotein PDB ID: 3FKE (Fig. 36 ), whose 3D structure was acquired from PDB [http:// www. rcsb. org/pdb/] with resolution range 1. 40 Ǻ. Antiviral compounds used for virtual screening were taken from PubChem database. The active site residues in the target proteins were determined by using CastP. Ligand preparation was done using Discovery studio software and their binding affinity with target components were analysed using Autodock 4. 0.
Materials and methods Examination of study participants shall be conducted according to the criteria of the Diagnostic_ and Statistical_ Manual of Mental Disorders, (DSM-IV-TR). Furthermore, defined in-and exclusion criteria shall apply. Whole exome sequencing shall be performed on the Illumina next sequencing platform at the King Fahad Medical Research Center, including methodology for sample preparation and quality control assessment, and production sequencing. Informatics upstream data analysis and interpretation shall be employed at the The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.
Results This project has started to recruit study participants according to the criteria outlined above. Literature review identified a number of case-control studies on biomarkers in ASD patients from Saudi Arabia which may support interpretation of our anticipated results. We propose that application of whole exome sequencing shall not only lead to the identification of possible pathogenic impairments in known ASD-related genes as listed in the Autism Database, (AutDB http://autism. mindspec. org/autdb/Welcome. do), but shall also result in identification of suspected ASD-related genes and ASD-related biological networks and pathways. Furthermore, we attempt to unravel novel genes not yet known to be related to ASD but may have a regional prevalence. This study aims also to contribute to leverage the involvement of the Canadian project partners in the international Autism Sequencing Consortium, which aims to decode approximately 10,000 autistic genomes.
Materials and methods We adopted a reductionist strategy and co-crystallised central core fragment of Aβ (16-21) with phospholipase A 2 (PLA 2 ) and report the complex structure at 1. 2 Å resolution (PDB id: 3JQL) determined by X-ray crystallography. The X-ray intensity data were collected on EMBL beamline X-11 at DESY, Hamburg with λ = 0. 98 Å, using MAR CCD detector. The data were processed using the programs DENZO and SCALEPACK  [5]. The crystals belong to space group P4 1 with unit cell parameters a = b = 42. 0 Å, c = 64. 1 Å containing four molecules in the unit cell. Good electron density for the peptide was observed at the active site of PLA 2.
These DSCs have direct impact on biological sex determination, embryonic development and require some medical, social and educational care  [4]. In Saudi Arabia, a systematic screening for DSCs is not implemented yet and only referred cases receive this diagnostic service. The objective is to assess the prevalence of most common DSCs in a Genomic Diagnostic Unit in KSA, determine the characteristics of the target population, and provide recommendations toward more comprehensive and multidisciplinary care for patients with DSCs. This study was performed using blood samples from 2256 consent patients referred to DGMU at CEGMR for subsequent cytogenetic or molecular analyses. Results Cytogenetic data analysis revealed an incidence of chromosomal abnormalities of 18. 35 % among all cases referred to DGMU.
Conclusions In this study we report that combination of RTK inhibitors with mTOR inhibitors show synergistic inhibition of AML cell lines and therefore offers a promising approach to deal with AML. However, not all SNVs occur at functionally equivalent positions, and it is important to consider the strength of functional importance of positions when prioritizing variants. We conducted a reanalysis of GWAS data by using the E-rank approach [1] that integrates evolutionary dimension into P-value in order to examine if additional bona-fide variant can be discovered.
Materials and methods We used data from an asthma GWAS of ~550,000 SNVs (PMID: 20860503)  [2]. For these variants, E-ranks and P-ranks were obtained from myPEG server. For the top 5000 E-rank variants, we obtained their replication which was reported to be significant in 45 sthma-related studies. This was done by querying the Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP v2. 0)  [3]. Written codes in "R" were used to compare E-rank and P-rank with replication and to estimate the genetic variance (GV) explained for each SNV according to this formula: GVi = 2 × log(ORi) 2 x MAFi (1-MAFi)  [4].
The heterozygous mother had mild cognitive impairment. Her X-chromosome inactivation pattern was not skewed. We identified a novel missense mutation (c. 1193G > A) in the OGT gene. This mutation was inherited by the affected males, and segregated with the abnormal phenotype. Rusults A single missense mutation (c. 1193G > A) was identified by X-exome sequencing of two patients, according to our filters this mutation is considered to be pathogenic. This mutation is absent from public databases of control individuals. Sanger sequencing was performed to confirm this novel mutation in all three affected boys as well as in the mother, also the unaffected brother X-exome sequencing revealed no mutation. This substitution is predicted to be deleterious by SIFT software (score: 0) and polyphen score was one which considered to be damaging.
Materials and methods The crystal structure of human PR (Id: 1SQN) was retrieved from Protein Data Bank as a template for docking DEHP and MEHP. The structures of DEHP and MEHP were obtained from PubChem database. Docking of DEHP and MEHP into the binding site of PR was performed using AutoDock 4. 2 with Lamarckian Genetic Algorithm to predict the bound conformation. The interacting residues for the ligand-receptor binding were visualized using Chimera.