The Genetic Landscape of a Cell

TLDR

The authors built a genome‑scale genetic interaction map by testing 5.4 million gene‑gene pairs, yielding quantitative interaction profiles for ~75 % of Saccharomyces cerevisiae genes. The resulting network maps a functional architecture of the yeast cell, clustering genes by biological process, revealing cross‑process connections, and showing that interaction degree correlates with gene attributes, thereby aiding interpretation of chemical‑genetic interactions and drug target discovery.

Abstract

A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for approximately 75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.