An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function

Hao Li, Xu Wang, Daria Rukina, Qingyao Huang, Tao Lin, Vincenzo Sorrentino, Hongbo Zhang, Maroun Bou Sleiman, Danny Arends, Aaron McDaid, Peiling Luan, Naveed Ziari, Laura A. Velázquez-Villegas, Karim Gariani, Zoltan Kutalik, Kristina Schoonjans, Richard A. Radcliffe, Pjotr Prins, Stephan Morgenthaler, Robert WilliamsJohan Auwerx

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Identifying genetic and environmental factors that impact complex traits and common diseases is a high biomedical priority. Here, we developed, validated, and implemented a series of multi-layered systems approaches, including (expression-based) phenome-wide association, transcriptome-/proteome-wide association, and (reverse-) mediation analysis, in an open-access web server (systems-genetics.org) to expedite the systems dissection of gene function. We applied these approaches to multi-omics datasets from the BXD mouse genetic reference population, and identified and validated associations between genes and clinical and molecular phenotypes, including previously unreported links between Rpl26 and body weight, and Cpt1a and lipid metabolism. Furthermore, through mediation and reverse-mediation analysis we established regulatory relations between genes, such as the co-regulation of BCKDHA and BCKDHB protein levels, and identified targets of transcription factors E2F6, ZFP277, and ZKSCAN1. Our multifaceted toolkit enabled the identification of gene-gene and gene-phenotype links that are robust and that translate well across populations and species, and can be universally applied to any populations with multi-omics datasets. Li et al. here develop and implement a series of systems tools and establish a web resource using multi-omics datasets of the BXD mouse cohort to identify novel associations between genes and phenotypes.

Original languageEnglish (US)
Pages (from-to)90-102.e4
JournalCell Systems
Volume6
Issue number1
DOIs
StatePublished - Jan 24 2018

Fingerprint

Genes
E2F6 Transcription Factor
Phenotype
Population Genetics
Proteome
Transcriptome
Lipid Metabolism
Population
Dissection
Body Weight
Datasets
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Li, H., Wang, X., Rukina, D., Huang, Q., Lin, T., Sorrentino, V., ... Auwerx, J. (2018). An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. Cell Systems, 6(1), 90-102.e4. https://doi.org/10.1016/j.cels.2017.10.016

An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. / Li, Hao; Wang, Xu; Rukina, Daria; Huang, Qingyao; Lin, Tao; Sorrentino, Vincenzo; Zhang, Hongbo; Bou Sleiman, Maroun; Arends, Danny; McDaid, Aaron; Luan, Peiling; Ziari, Naveed; Velázquez-Villegas, Laura A.; Gariani, Karim; Kutalik, Zoltan; Schoonjans, Kristina; Radcliffe, Richard A.; Prins, Pjotr; Morgenthaler, Stephan; Williams, Robert; Auwerx, Johan.

In: Cell Systems, Vol. 6, No. 1, 24.01.2018, p. 90-102.e4.

Research output: Contribution to journalArticle

Li, H, Wang, X, Rukina, D, Huang, Q, Lin, T, Sorrentino, V, Zhang, H, Bou Sleiman, M, Arends, D, McDaid, A, Luan, P, Ziari, N, Velázquez-Villegas, LA, Gariani, K, Kutalik, Z, Schoonjans, K, Radcliffe, RA, Prins, P, Morgenthaler, S, Williams, R & Auwerx, J 2018, 'An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function', Cell Systems, vol. 6, no. 1, pp. 90-102.e4. https://doi.org/10.1016/j.cels.2017.10.016
Li H, Wang X, Rukina D, Huang Q, Lin T, Sorrentino V et al. An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. Cell Systems. 2018 Jan 24;6(1):90-102.e4. https://doi.org/10.1016/j.cels.2017.10.016
Li, Hao ; Wang, Xu ; Rukina, Daria ; Huang, Qingyao ; Lin, Tao ; Sorrentino, Vincenzo ; Zhang, Hongbo ; Bou Sleiman, Maroun ; Arends, Danny ; McDaid, Aaron ; Luan, Peiling ; Ziari, Naveed ; Velázquez-Villegas, Laura A. ; Gariani, Karim ; Kutalik, Zoltan ; Schoonjans, Kristina ; Radcliffe, Richard A. ; Prins, Pjotr ; Morgenthaler, Stephan ; Williams, Robert ; Auwerx, Johan. / An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. In: Cell Systems. 2018 ; Vol. 6, No. 1. pp. 90-102.e4.
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