TitleA global genetic interaction network maps a wiring diagram of cellular function.
Publication TypeJournal Article
Year of Publication2016
AuthorsCostanzo, M, VanderSluis, B, Koch, EN, Baryshnikova, A, Pons, C, Tan, G, Wang, W, Usaj, M, Hanchard, J, Lee, SD, Pelechano, V, Styles, EB, Billmann, M, van Leeuwen, J, van Dyk, N, Lin, Z-Y, Kuzmin, E, Nelson, J, Piotrowski, JS, Srikumar, T, Bahr, S, Chen, Y, Deshpande, R, Kurat, CF, Li, SC, Li, Z, Usaj, MMattiazzi, Okada, H, Pascoe, N, San Luis, B-J, Sharifpoor, S, Shuteriqi, E, Simpkins, SW, Snider, J, Suresh, HGaradi, Tan, Y, Zhu, H, Malod-Dognin, N, Janjic, V, Przulj, N, Troyanskaya, OG, Stagljar, I, Xia, T, Ohya, Y, Gingras, A-C, Raught, B, Boutros, M, Steinmetz, LM, Moore, CL, Rosebrock, AP, Caudy, AA, Myers, CL, Andrews, B, Boone, C
JournalScience
Volume353
Issue6306
Date Published2016 09 23
ISSN1095-9203
KeywordsEpistasis, Genetic, Gene Regulatory Networks, Genes, Essential, Genes, Fungal, Genetic Pleiotropy, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Abstract

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.
DOI10.1126/science.aaf1420
Alternate JournalScience
PubMed ID27708008
PubMed Central IDPMC5661885
Grant ListR01 HG005084 / HG / NHGRI NIH HHS / United States
R01 HG005853 / HG / NHGRI NIH HHS / United States
294542 / / European Research Council / International
FDN-143265 / / CIHR / Canada
FDN-143264 / / CIHR / Canada
R01 GM104975 / GM / NIGMS NIH HHS / United States