A global genetic interaction network maps a wiring diagram of cellular function

Costanzo M; VanderSluis B; Koch EN; Baryshnikova A; Pons C; Tan GH; Wang W; Usaj M; Hanchard J; Lee SD; Pelechano V; Styles EB; Billmann M; van Leeuwen J; van Dyk N; Lin ZY; Kuzmin E; Nelson J; Piotrowski JS; Srikumar T; Bahr S; Chen YQ; Deshpande R; Kurat CF; Li SC; Li ZJ; Usaj MM; Okada H; Pascoe N; San Luis BJ; Sharifpoor S; Shuteriqi E; Simpkins SW; Snider J; Suresh HG; Tan YZ; Zhu HW; Malod-Dognin N; Janjic V; Przulj N; Troyanskaya OG; Stagljar I; Xia T; Ohya Y; Gingras AC; Raught B; Boutros M; Steinmetz LM; Moore CL; Rosebrock AP; Caudy AA; Myers CL; Andrews B; Boone C

Science, Vol.353, No.6306, 1381-1381, 2016

DOI10.1126/science.aaf1420 Export Citation

A global genetic interaction network maps a wiring diagram of cellular function

Costanzo M, VanderSluis B, Koch EN, Baryshnikova A, Pons C, Tan GH, Wang W, Usaj M, Hanchard J, Lee SD, Pelechano V, Styles EB, Billmann M, van Leeuwen J, van Dyk N, Lin ZY, Kuzmin E, Nelson J, Piotrowski JS, Srikumar T, Bahr S, Chen YQ, Deshpande R, Kurat CF, Li SC, Li ZJ, Usaj MM, Okada H, Pascoe N, San Luis BJ, Sharifpoor S, Shuteriqi E, Simpkins SW, Snider J, Suresh HG, Tan YZ, Zhu HW, Malod-Dognin N, Janjic V, Przulj N, Troyanskaya OG, Stagljar I, Xia T, Ohya Y, Gingras AC, Raught B, Boutros M, Steinmetz LM, Moore CL, Rosebrock AP, Caudy AA, Myers CL, Andrews B, Boone C

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.