Integrative Analysis of Transcriptomic and Epigenomic Data to Reveal Regulation Patterns for Osteoporosis Risk
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE62589 | GEO | 2014/10/22
SECONDARY ACCESSION(S): PRJNA264477
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-22 | E-GEOD-62589 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
2014-10-22 | E-GEOD-62588 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
2014-11-19 | E-GEOD-63446 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. 5 high hip BMD subjects and 5 low hip BMD subjects
2014-10-17 | E-GEOD-62402 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.
2014-10-22 | GSE62588 | GEO
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.
2014-10-17 | GSE62402 | GEO
Project description:In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.
2014-11-19 | GSE63446 | GEO
Project description:Integration of multiple profiling data and construction of functional gene networks may provide additional insights into the molecular mechanisms of complex diseases. Osteoporosis is a worldwide public health problem, but the complex gene-gene interactions, post-transcriptional modifications and regulation of functional networks are still unclear. To gain a comprehensive understanding of osteoporosis etiology, transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing were performed simultaneously in 5 high hip BMD (Bone Mineral Density) subjects and 5 low hip BMD subjects. SPIA (Signaling Pathway Impact Analysis) and PCST (Prize Collecting Steiner Tree) algorithm were used to perform pathway-enrichment analysis and construct the interaction networks. Through integrating the transcriptomic and epigenomic data, firstly we identified 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) which showed the consistent association evidence from both gene expression and methylation data; secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status. In conclusion, the integration of multiple layers of omics can yield in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.
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Project description:Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases.
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Project description:BackgroundRegulation of transcription is central to the emergence of new cell types during development, and it often involves activation of genes via proximal and distal regulatory regions. The activity of regulatory elements is determined by transcription factors (TFs) and epigenetic marks, but despite extensive mapping of such patterns, the extraction of regulatory principles remains challenging.ResultsHere we study differentially and similarly expressed genes along with their associated epigenomic profiles, chromatin accessibility and DNA methylation, during lineage specification at gastrulation in mice. Comparison of the three lineages allows us to identify genomic and epigenomic features that distinguish the two classes of genes. We show that differentially expressed genes are primarily regulated by distal elements, while similarly expressed genes are controlled by proximal housekeeping regulatory programs. Differentially expressed genes are relatively isolated within topologically associated domains, while similarly expressed genes tend to be located in gene clusters. Transcription of differentially expressed genes is associated with differentially open chromatin at distal elements including enhancers, while that of similarly expressed genes is associated with ubiquitously accessible chromatin at promoters.ConclusionBased on these associations of (linearly) distal genes' transcription start sites (TSSs) and putative enhancers for developmental genes, our findings allow us to link putative enhancers to their target promoters and to infer lineage-specific repertoires of putative driver transcription factors, within which we define subgroups of pioneers and co-operators.
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