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Article: Identification of Regulatory Modules That Stratify Lupus Disease Mechanism through Integrating Multi-Omics Data

TitleIdentification of Regulatory Modules That Stratify Lupus Disease Mechanism through Integrating Multi-Omics Data
Authors
Keywordssystemic lupus erythematosus
integrative analysis
gene expression
protein-protein interactions
transcription factor
Issue Date2020
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content
Citation
Molecular Therapy - Nucleic Acids, 2020, v. 19, p. 318-329 How to Cite?
AbstractAlthough recent advances in genetic studies have shed light on systemic lupus erythematosus (SLE), its detailed mechanisms remain elusive. In this study, using datasets on SLE transcriptomic profiles, we identified 750 differentially expressed genes (DEGs) in T and B lymphocytes and peripheral blood cells. Using transcription factor (TF) binding data derived from chromatin immunoprecipitation sequencing (ChIP-seq) experiments from the Encyclopedia of DNA Elements (ENCODE) project, we inferred networks of co-regulated genes (NcRGs) based on binding profiles of the upregulated DEGs by significantly enriched TFs. Modularization analysis of NcRGs identified co-regulatory modules among the DEGs and master TFs vital for each module. Remarkably, the co-regulatory modules stratified the common SLE interferon (IFN) signature and revealed SLE pathogenesis pathways, including the complement cascade, cell cycle regulation, NETosis, and epigenetic regulation. By integrative analyses of disease-associated genes (DAGs), DEGs, and enriched TFs, as well as proteins interacting with them, we identified a hierarchical regulatory cascade with TFs regulated by DAGs, which in turn regulates gene expression. Integrative analysis of multi-omics data provided valuable molecular insights into the molecular mechanisms of SLE.
Persistent Identifierhttp://hdl.handle.net/10722/285310
ISSN
2020 Impact Factor: 8.886
2015 SCImago Journal Rankings: 2.320
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWANG, TY-
dc.contributor.authorWang, YF-
dc.contributor.authorZhang, Y-
dc.contributor.authorSHEN, JJ-
dc.contributor.authorGUO, M-
dc.contributor.authorYang, J-
dc.contributor.authorLau, YL-
dc.contributor.authorYang, W-
dc.date.accessioned2020-08-18T03:52:18Z-
dc.date.available2020-08-18T03:52:18Z-
dc.date.issued2020-
dc.identifier.citationMolecular Therapy - Nucleic Acids, 2020, v. 19, p. 318-329-
dc.identifier.issn2162-2531-
dc.identifier.urihttp://hdl.handle.net/10722/285310-
dc.description.abstractAlthough recent advances in genetic studies have shed light on systemic lupus erythematosus (SLE), its detailed mechanisms remain elusive. In this study, using datasets on SLE transcriptomic profiles, we identified 750 differentially expressed genes (DEGs) in T and B lymphocytes and peripheral blood cells. Using transcription factor (TF) binding data derived from chromatin immunoprecipitation sequencing (ChIP-seq) experiments from the Encyclopedia of DNA Elements (ENCODE) project, we inferred networks of co-regulated genes (NcRGs) based on binding profiles of the upregulated DEGs by significantly enriched TFs. Modularization analysis of NcRGs identified co-regulatory modules among the DEGs and master TFs vital for each module. Remarkably, the co-regulatory modules stratified the common SLE interferon (IFN) signature and revealed SLE pathogenesis pathways, including the complement cascade, cell cycle regulation, NETosis, and epigenetic regulation. By integrative analyses of disease-associated genes (DAGs), DEGs, and enriched TFs, as well as proteins interacting with them, we identified a hierarchical regulatory cascade with TFs regulated by DAGs, which in turn regulates gene expression. Integrative analysis of multi-omics data provided valuable molecular insights into the molecular mechanisms of SLE.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content-
dc.relation.ispartofMolecular Therapy - Nucleic Acids-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectsystemic lupus erythematosus-
dc.subjectintegrative analysis-
dc.subjectgene expression-
dc.subjectprotein-protein interactions-
dc.subjecttranscription factor-
dc.titleIdentification of Regulatory Modules That Stratify Lupus Disease Mechanism through Integrating Multi-Omics Data-
dc.typeArticle-
dc.identifier.emailWang, YF: yfwangbm@connect.hku.hk-
dc.identifier.emailYang, J: jingy09@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.omtn.2019.11.019-
dc.identifier.pmid31877408-
dc.identifier.pmcidPMC6938958-
dc.identifier.scopuseid_2-s2.0-85076706746-
dc.identifier.hkuros312930-
dc.identifier.volume19-
dc.identifier.spage318-
dc.identifier.epage329-
dc.identifier.isiWOS:000519557700028-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2162-2531-

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