RT Journal
A1 Bellay, Jeremy
A1 Atluri, Gowtham
A1 Sing, Tina L.
A1 Toufighi, Kiana
A1 Costanzo, Michael
A1 Ribeiro, Philippe Souza Moraes
A1 Pandey, Gaurav
A1 Baller, Joshua
A1 VanderSluis, Benjamin
A1 Michaut, Magali
A1 Han, Sangjo
A1 Kim, Philip
A1 Brown, Grant W.
A1 Andrews, Brenda J.
A1 Boone, Charles
A1 Kumar, Vipin
A1 Myers, Chad L.
T1 Putting genetic interactions in context through a global modular decomposition
JF Genome Research 
JO Genome Research 
YR 2011 
FD August 01 
VO 21 
IS 8 
SP 1375 
OP 1387 
DO 10.1101/gr.117176.110 
UL http://genome.cshlp.org/content/21/8/1375.abstract 
AB Genetic interactions provide a powerful perspective into gene function, but our knowledge of the specific mechanisms that give rise to these interactions is still relatively limited. The availability of a global genetic interaction map in Saccharomyces cerevisiae, covering ∼30% of all possible double mutant combinations, provides an unprecedented opportunity for an unbiased assessment of the native structure within genetic interaction networks and how it relates to gene function and modular organization. Toward this end, we developed a data mining approach to exhaustively discover all block structures within this network, which allowed for its complete modular decomposition. The resulting modular structures revealed the importance of the context of individual genetic interactions in their interpretation and revealed distinct trends among genetic interaction hubs as well as insights into the evolution of duplicate genes. Block membership also revealed a surprising degree of multifunctionality across the yeast genome and enabled a novel association of VIP1 and IPK1 with DNA replication and repair, which is supported by experimental evidence. Our modular decomposition also provided a basis for testing the between-pathway model of negative genetic interactions and within-pathway model of positive genetic interactions. While we find that most modular structures involving negative genetic interactions fit the between-pathway model, we found that current models for positive genetic interactions fail to explain 80% of the modular structures detected. We also find differences between the modular structures of essential and nonessential genes.