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Klaus, V. ; Schriever, S.C. ; Monroy Kuhn, J.M. ; Peter, A. ; Irmler, M. ; Tokarz, J. ; Prehn, C. ; Kastenmüller, G. ; Beckers, J. ; Adamski, J. ; Königsrainer, A.* ; Müller, T.D. ; Heni, M. ; Tschöp, M.H. ; Pfluger, P.T. ; Lutter, D.

Correlation guided Network Integration (CoNI) reveals novel genes affecting hepatic metabolism.

Mol. Metab. 53, 101295 (2021)

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	Open Access Gold

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Technological advances have brought a steady increase in the availability of various types of omics data, from genomics to metabolomics. Integrating these multi-omics data is a chance and challenge for systems biology, yet tools to fully tap their potential remain scarce. We here present a fully unsupervised and versatile correlation-based method, termed Correlation guided Network Integration (CoNI), to integrate multi-omics data into a hypergraph structure that allows for the identification of effective modulators of metabolism. Our approach yields single transcripts of potential relevance that map to specific, densely connected metabolic sub-graphs or pathways. By applying our method on transcriptomics and metabolomics data from murine livers under standard Chow or high-fat diet, we identified eleven genes with potential regulatory effects on hepatic metabolism. Five candidates, including the hepatokine INHBE, were validated in human liver biopsies to correlate with diabetes-related traits such as overweight, hepatic fat content, and insulin resistance (HOMA-IR). Our method's successful application to an independent omics dataset confirmed that the novel CoNI framework is a transferable, entirely data-driven, flexible, and versatile tool for multiple omics data integration and interpretation.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Data Integration ; Hepatic Steatosis ; Multi Omics ; Systems Biology; Insulin-resistance; Transgenic Mice; Myc; Aquaporin-7; Homeostasis; Obesity; Atlas

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 53, Pages: 101295

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)

Grants Initiative and Networking Fund of the Helmholtz Association
Helmholtz Alliance Aging and Metabolic Programming (AMPro)
Helmholtz Initiative for Personalized Medicine (iMed)
DZD tandem grant funds (SCS, PP, MH)
Alexander von Humboldt Foundation
Helmholtz Portfolio Program "Metabolic Dysfunction"
German Research Foundation (DFG)
German Federal Ministry of Education and Research (BMBF)