cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29291251.v1
title: The myoblast methylome: multiple types of associations with chromatin and transcription

description: Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (<i>e.g</i>., <i>SIM2</i> and <i>TWIST1</i>). In contrast, brain-specific <i>OLIG2</i> was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The <i>OLIG2</i>-linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.
DOI: 10.6084/m9.figshare.29291251.v2
title: The myoblast methylome: multiple types of associations with chromatin and transcription

description: Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (<i>e.g</i>., <i>SIM2</i> and <i>TWIST1</i>). In contrast, brain-specific <i>OLIG2</i> was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The <i>OLIG2</i>-linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.
DOI: 10.6084/m9.figshare.28730254
title: A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci

description: Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (<i>p</i> &lt; 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (<i>p</i> &lt; 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (<i>p</i> &lt; 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.
DOI: 10.6084/m9.figshare.28730254.v1
title: A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci

description: Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (<i>p</i> &lt; 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (<i>p</i> &lt; 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (<i>p</i> &lt; 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.
DOI: 10.6084/m9.figshare.28941785
title: DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study

description: Insulin resistance (IR) is a risk factor for cardiovascular diseases and type 2 diabetes. Associations between DNA methylation (DNAm) and IR have been less studied in African ancestry (AA) populations than those of European ancestry (EA). We aimed to identify associations between whole blood DNAm and IR in up to 1,811 AA and 964 EA participants from the Atherosclerosis Risk in Communities (ARIC) study. We quantified IR using three surrogate measures: the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose index (TyG), and the triglyceride glucose-body mass index (TyG-BMI). We used ancestry-stratified linear regression models to conduct epigenome-wide association studies of IR, adjusting for batch effects and relevant covariates. Among 484,436 tested CpG sites, 39 were significantly associated with IR, of which 31% (10 in AA and two in EA) were associated with TyG-BMI and not previously reported for IR or related traits. These include a positive association at cg18335991-<i>SEMA7A</i> in AA. <i>SEMA7A</i> inhibits adipogenesis of preadipocytes and lipogenesis of mature adipocytes. DNAm levels at cg18335991 have been reported to be negatively associated with <i>SEMA7A</i> expression in blood. After additionally adjusting for smoking and drinking status, 15 of the 39 significant CpG sites remained significant or suggestive. Our study identified novel IR-associated CpG sites, contributing to a broader understanding of the epigenetic mechanisms underlying IR in diverse populations. Associations between DNA methylation (DNAm) and insulin resistance (IR) have been primarily studied in individuals of European ancestry. The epigenetic regulation of IR, quantified using different surrogate measures, has not been extensively reported in diverse populations.This study aimed to identify associations between DNAm and IR in African and European ancestries and assessed how these associations differ by IR surrogate measures.Among 39 significant IR-associated CpG sites, 12 CpG sites, associated with the triglyceride glucose-body mass index, were potentially novel, and most were detected in African ancestry participants.This study improves our understanding of the epigenetic mechanisms underlying IR in diverse populations. Associations between DNA methylation (DNAm) and insulin resistance (IR) have been primarily studied in individuals of European ancestry. The epigenetic regulation of IR, quantified using different surrogate measures, has not been extensively reported in diverse populations. This study aimed to identify associations between DNAm and IR in African and European ancestries and assessed how these associations differ by IR surrogate measures. Among 39 significant IR-associated CpG sites, 12 CpG sites, associated with the triglyceride glucose-body mass index, were potentially novel, and most were detected in African ancestry participants. This study improves our understanding of the epigenetic mechanisms underlying IR in diverse populations.
DOI: 10.6084/m9.figshare.29218016
title: A novel lncRNA, Lnc21q22.11, suppresses gastric cancer growth by inhibiting MEK/ERK pathway

description: Gastric cancer (GC) is one of the most common malignancies with limited treatment options and poor prognosis. Therefore, it is necessary to identify new markers for the development of novel therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as pivotal players in cancer. However, RNA-based cancer therapy has been challenged by non-specificity and adverse immune effects. Thus, a comprehensive understanding of the functional roles of lncRNAs and their regulatory networks in downstream pathways may provide more specific targets. In this study, we identified a novel lncRNA, Lnc21q22.11, encoded by the region of chromosome 21q22.11. The full-length transcript was 1202 nt, and its expression was reduced in GC. The expression of Lnc21q22.11 was regulated by histone methylation. Lnc21q22.11 inhibited GC cell proliferation, colony formation, invasion, and migration. Lnc21q22.11 suppressed N87 cell xenograft growth in mice. Mechanistically, Lnc21q22.11 inhibited the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway by interacting with MYH9 in GC cells. Loss of or reduced Lnc21q22.11 expression sensitized GC cells to MEK inhibitor. In conclusion, Lnc21q22.11 is a novel lncRNA in gastric cancer. It suppresses gastric cancer growth by inhibiting the MEK/ERK signaling pathway both <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 is a novel lncRNA with the full length obtained. • The expression of Lnc21q22.11 is regulated by histone modification. • Lnc21q22.11 suppresses gastric cancer growth both <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 inhibits MEK/ERK signaling pathway by interacting with MYH9.
DOI: 10.6084/m9.figshare.29218016.v1
title: A novel lncRNA, Lnc21q22.11, suppresses gastric cancer growth by inhibiting MEK/ERK pathway

description: Gastric cancer (GC) is one of the most common malignancies with limited treatment options and poor prognosis. Therefore, it is necessary to identify new markers for the development of novel therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as pivotal players in cancer. However, RNA-based cancer therapy has been challenged by non-specificity and adverse immune effects. Thus, a comprehensive understanding of the functional roles of lncRNAs and their regulatory networks in downstream pathways may provide more specific targets. In this study, we identified a novel lncRNA, Lnc21q22.11, encoded by the region of chromosome 21q22.11. The full-length transcript was 1202 nt, and its expression was reduced in GC. The expression of Lnc21q22.11 was regulated by histone methylation. Lnc21q22.11 inhibited GC cell proliferation, colony formation, invasion, and migration. Lnc21q22.11 suppressed N87 cell xenograft growth in mice. Mechanistically, Lnc21q22.11 inhibited the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway by interacting with MYH9 in GC cells. Loss of or reduced Lnc21q22.11 expression sensitized GC cells to MEK inhibitor. In conclusion, Lnc21q22.11 is a novel lncRNA in gastric cancer. It suppresses gastric cancer growth by inhibiting the MEK/ERK signaling pathway both <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 is a novel lncRNA with the full length obtained. • The expression of Lnc21q22.11 is regulated by histone modification. • Lnc21q22.11 suppresses gastric cancer growth both <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 inhibits MEK/ERK signaling pathway by interacting with MYH9.
DOI: 10.6084/m9.figshare.29062481
title: Chromatin accessibility profiling of Treg cells in acute urticaria

description: Acute urticaria can be a presenting symptom of anaphylaxis characterized by transient red swellings or fulminant wheals, often accompanied by severe pruritus. Numerous studies have substantiated the important involvement of regulatory T cells (Tregs) in the occurrence of allergic diseases and autoimmune diseases. However, the role of Tregs in the pathogenesis of acute urticaria is unclear. In this study, we found that the frequency of Tregs in peripheral blood mononuclear cells (PBMCs) was decreased in patients with acute urticaria compared with normal controls by flow cytometry. Analysis of Assay for transposase-accessible chromatin with sequencing (ATAC-seq) data identified 28 differentially accessible regions comparing Tregs from healthy individuals and patients with acute urticaria, all showing increased chromatin accessibility in the Tregs from acute urticaria. IL-1b was highly expressed in sera of patients with acute urticaria and the level of IL-1b was moderately positively related to white blood cell count. The elevated expression of IL-1b may be due to the diminished immune-suppressive function following the decline of Tregs in this study. We found that <i>IL1B</i> gene expression was also significantly increased in the skin lesions of both chronic spontaneous urticaria and solar urticaria compared to healthy controls. IL1B might play a key role in the development of acute urticaria and IL1B could be a potential prognostic biomarker and therapeutic target in urticaria. In patients with acute urticaria, the proportion of special immune cells called regulatory T cells in their blood was lower compared to healthy individuals.A special test called ATAC-seq found 28 areas in the DNA of regulatory T cells that are more easily accessed in patient with acute urticaria than in healthy individuals.A molecule called IL1B was found to be increased in the blood and skin of patients with different forms of urticaria and might be involved in the condition. In patients with acute urticaria, the proportion of special immune cells called regulatory T cells in their blood was lower compared to healthy individuals. A special test called ATAC-seq found 28 areas in the DNA of regulatory T cells that are more easily accessed in patient with acute urticaria than in healthy individuals. A molecule called IL1B was found to be increased in the blood and skin of patients with different forms of urticaria and might be involved in the condition.
DOI: 10.6084/m9.figshare.29062481.v1
title: Chromatin accessibility profiling of Treg cells in acute urticaria

description: Acute urticaria can be a presenting symptom of anaphylaxis characterized by transient red swellings or fulminant wheals, often accompanied by severe pruritus. Numerous studies have substantiated the important involvement of regulatory T cells (Tregs) in the occurrence of allergic diseases and autoimmune diseases. However, the role of Tregs in the pathogenesis of acute urticaria is unclear. In this study, we found that the frequency of Tregs in peripheral blood mononuclear cells (PBMCs) was decreased in patients with acute urticaria compared with normal controls by flow cytometry. Analysis of Assay for transposase-accessible chromatin with sequencing (ATAC-seq) data identified 28 differentially accessible regions comparing Tregs from healthy individuals and patients with acute urticaria, all showing increased chromatin accessibility in the Tregs from acute urticaria. IL-1b was highly expressed in sera of patients with acute urticaria and the level of IL-1b was moderately positively related to white blood cell count. The elevated expression of IL-1b may be due to the diminished immune-suppressive function following the decline of Tregs in this study. We found that <i>IL1B</i> gene expression was also significantly increased in the skin lesions of both chronic spontaneous urticaria and solar urticaria compared to healthy controls. IL1B might play a key role in the development of acute urticaria and IL1B could be a potential prognostic biomarker and therapeutic target in urticaria. In patients with acute urticaria, the proportion of special immune cells called regulatory T cells in their blood was lower compared to healthy individuals.A special test called ATAC-seq found 28 areas in the DNA of regulatory T cells that are more easily accessed in patient with acute urticaria than in healthy individuals.A molecule called IL1B was found to be increased in the blood and skin of patients with different forms of urticaria and might be involved in the condition. In patients with acute urticaria, the proportion of special immune cells called regulatory T cells in their blood was lower compared to healthy individuals. A special test called ATAC-seq found 28 areas in the DNA of regulatory T cells that are more easily accessed in patient with acute urticaria than in healthy individuals. A molecule called IL1B was found to be increased in the blood and skin of patients with different forms of urticaria and might be involved in the condition.
DOI: 10.6084/m9.figshare.30836710
title: Exploring the association between DNA methylation and pancreatic cancer susceptibility through epigenome-wide Mendelian randomization and multi-omics data integration

description: Investigating the role of DNA methylation in the development of pancreatic cancer (PC) may facilitate identification of potential targets for both diagnosis and treatment. We carried out a comprehensive epigenome-wide Mendelian randomization (EWMR) analysis to investigate the correlation of genetically predicted blood CpG sites with PC. Following this, we conducted various sensitivity analyses and repeated analyses using different selection criteria for instrumental variables and conditional Bayesian colocalization to guarantee the reliability of the results. External validation and a meta-analysis were then performed to further validate these results. Next, we conducted CpG site enrichment analysis, overlap with phenome-wide association studies (PheWAS) catalog analysis, overlap with epigenome-wide association studies (EWAS) Toolkit analysis, and drug target analysis to explore the enrichment, biological functions, and potential therapeutic targets associated with these sites. Finally, we used the SMR-IVW software to perform mediation analysis, aiming to uncover potential tumorigenesis pathways of PC at the transcriptional level from three distinct perspectives. Results showed 253 CpG sites passing sensitivity analysis were significantly associated with PC and 159 CpG sites were validated in at least one replication. After meta-analysis, 38 CpG sites were retained, and all 253 CpG sites were classified into three tiers. Among these, cg26373071 (CLPTM1L), cg14271713, cg11652496 (PSTPIP1), and cg20575191 (PSTPIP1) were placed in tier 1 with strong support. Finally, this study identified genetic susceptibility linked to 253 PC-related CpG sites. This study provides insights into the disease’s origins and underscores potential targets for future research.
DOI: 10.6084/m9.figshare.30836710.v1
title: Exploring the association between DNA methylation and pancreatic cancer susceptibility through epigenome-wide Mendelian randomization and multi-omics data integration

description: Investigating the role of DNA methylation in the development of pancreatic cancer (PC) may facilitate identification of potential targets for both diagnosis and treatment. We carried out a comprehensive epigenome-wide Mendelian randomization (EWMR) analysis to investigate the correlation of genetically predicted blood CpG sites with PC. Following this, we conducted various sensitivity analyses and repeated analyses using different selection criteria for instrumental variables and conditional Bayesian colocalization to guarantee the reliability of the results. External validation and a meta-analysis were then performed to further validate these results. Next, we conducted CpG site enrichment analysis, overlap with phenome-wide association studies (PheWAS) catalog analysis, overlap with epigenome-wide association studies (EWAS) Toolkit analysis, and drug target analysis to explore the enrichment, biological functions, and potential therapeutic targets associated with these sites. Finally, we used the SMR-IVW software to perform mediation analysis, aiming to uncover potential tumorigenesis pathways of PC at the transcriptional level from three distinct perspectives. Results showed 253 CpG sites passing sensitivity analysis were significantly associated with PC and 159 CpG sites were validated in at least one replication. After meta-analysis, 38 CpG sites were retained, and all 253 CpG sites were classified into three tiers. Among these, cg26373071 (CLPTM1L), cg14271713, cg11652496 (PSTPIP1), and cg20575191 (PSTPIP1) were placed in tier 1 with strong support. Finally, this study identified genetic susceptibility linked to 253 PC-related CpG sites. This study provides insights into the disease’s origins and underscores potential targets for future research.
DOI: 10.6084/m9.figshare.28776613
title: Differential methylation in blood pressure control genes is associated to essential hypertension in African Brazilian populations

description: While genetic studies have provided insights into essential hypertension (EH, defined by high blood pressure ≥140/90 mmHg), investigation through epigenetics may address gaps in understanding its heritability. This study focused on African Brazilian populations in Vale do Ribeira River region, due to their high hypertension prevalence. We aimed to determine if DNA methylation is linked to hypertension susceptibility, through a genome-wide evaluation of 80 peripheral blood samples from normotensive (39) and hypertensive (41) individuals, with Infinium Methylation EPIC BeadChip platform. Data were analyzed using ChAMP package and cross-referenced with information from databases such as EWAS Atlas, GWAS catalog, GeneCards, literature, and tools such as VarElect and EWAS Toolkit. The comparison between hypertensive and normotensive revealed 190 differentially methylated CpG positions (DMPs) and 46 differentially methylated regions (DMRs), both with <i>p</i>-value ≤0.05. Among the DMPs, 27 were found to have a plausible role in blood pressure. Among the DMRs, those mapped to <i>ABAT, BLCAP, CERS3, EIF4E, FMN1, GABBR1, HLA-DQB2, HOXA5, IL5RA, KCNH2, MIR487B, MIR539, MIR886, MKRN3, NUDT12, PON3, RNF39, RWDD3,</i> and <i>TSHBS1</i> were highlighted because of their lowest <i>p</i>-values, current literature, and/or VarElect prioritization. Our findings suggest that differences in methylation contribute to the high susceptibility to essential hypertension in these populations.