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https://doi.org/10.1016/j.cels.2017.10.016
Title: | An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function | Authors: | Li, Hao Wang, Xu Rukina, Daria Huang, Qingyao Lin, Tao Sorrentino, Vincenzo Zhang, Hongbo Sleiman, Maroun Bou Arends, Danny McDaid, Aaron Luan, Peiling Ziari, Naveed Velazquez-Villegas, Laura A Gariani, Karim Kutalik, Zoltan Schoonjans, Kristina Radcliffe, Richard A Prins, Pjotr Morgenthaler, Stephan Williams, Robert W Auwerx, Johan |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Cell Biology GENOME-WIDE ASSOCIATION CANCER GENOMICS COMPLEX TRAITS EXPRESSION DISEASE IDENTIFICATION ARCHITECTURE TRANSPORTER DISSECTION PHENOTYPE |
Issue Date: | 24-Jan-2018 | Publisher: | CELL PRESS | Citation: | Li, Hao, Wang, Xu, Rukina, Daria, Huang, Qingyao, Lin, Tao, Sorrentino, Vincenzo, Zhang, Hongbo, Sleiman, Maroun Bou, Arends, Danny, McDaid, Aaron, Luan, Peiling, Ziari, Naveed, Velazquez-Villegas, Laura A, Gariani, Karim, Kutalik, Zoltan, Schoonjans, Kristina, Radcliffe, Richard A, Prins, Pjotr, Morgenthaler, Stephan, Williams, Robert W, Auwerx, Johan (2018-01-24). An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. CELL SYSTEMS 6 (1) : 90-102. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cels.2017.10.016 | 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. | Source Title: | CELL SYSTEMS | URI: | https://scholarbank.nus.edu.sg/handle/10635/247800 | ISSN: | 2405-4712 2405-4720 |
DOI: | 10.1016/j.cels.2017.10.016 |
Appears in Collections: | Staff Publications Elements |
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