Global Mapping of the Yeast Genetic Interaction Network

Abstract

A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

Systematic interpretation of genetic interactions using protein networks

“…These interactions comprise a physical network, which correlates with the network of genetic interactions and provides potential clues as to the mechanisms behind particular synthetic-lethal effects. Previous studies have demonstrated this correlated structure in yeast, by showing that two proteins in the same region of the genetic network are likely to also physically interact 8,10 , that genes with similar patterns of genetic interactions often occur within the same protein complex 10 and that a protein with many interactions in the physical network typically has many interactions in the genetic network also 20 .…”

“…1). The first was generated by SGA, a large-scale screen 10 crossing 132 yeast gene deletion strains versus each of the ~4,700 available deletion strains 22 and resulting in 2,012 observed synthetic-lethal interactions and 2,113 synthetic-sick interactions. The second data source consisted of an additional 687 synthetic-lethal interactions culled from the literature and catalogued at the Munich Information Center for Protein Sequences (MIPS) 23 .…”

“…1 online and Tong et al 8,10 ), but demonstrate a need for structured models to efficiently separate signal from noise. Towards this goal, we implemented a probabilistic modeling procedure to capture the between-pathway interpretation of genetic interactions.…”

“…However, interpreting the functional significance of each result remains a relatively slow process. The problem is compounded by the large number of genetic interactions measured when screening one gene versus all others (~34 on average 10 ) as well as possible false positives if the interactions are not confirmed by tetrad or random spore analysis. Thus, without further methods to aid in characterizing synthetic lethals, large-scale interpretation is a daunting prospect.…”

Expanding the Functional Repertoire of CTD Kinase I and RNA Polymerase II: Novel PhosphoCTD-Associating Proteins in the Yeast Proteome

“…Similar profiles were observed for almost all such complexes as described in either ref 70 or ref 69 (see Table 1 of Supporting Information and Discussion). Intriguingly, in addition to such physical interactions, these proteins also interact with each other genetically [SGD, Saccharomyces Genome Database, http://www.yeastgenome.org/ (58,71,72)], indicating that the observed physical interactions also have functional significance in vivo (Table 2 of Supporting Information). In addition, several of the proteins have been found to interact genetically with genes encoding transcription elongation-related functions, such as CDC73 (58,71,72).…”