» Articles » PMID: 20093466

The Genetic Landscape of a Cell

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.

Citing Articles

Characterization and optimization of mnn11Δ-mediated enhancement in heterologous protein production in Kluyveromyces marxianus.

Zhou S, Wu P, Ren H, Zhou J, Yu Y, Lu H Microb Cell Fact. 2025; 24(1):50.

PMID: 40033357 PMC: 11877904. DOI: 10.1186/s12934-025-02676-2.


dotears: Scalable and consistent directed acyclic graph estimation using observational and interventional data.

Xue A, Rao J, Sankararaman S, Pimentel H iScience. 2025; 28(2):111673.

PMID: 39944273 PMC: 11814701. DOI: 10.1016/j.isci.2024.111673.


Simplicity within biological complexity.

Przulj N, Malod-Dognin N Bioinform Adv. 2025; 5(1):vbae164.

PMID: 39927291 PMC: 11805345. DOI: 10.1093/bioadv/vbae164.


Saturated Transposon Analysis in Yeast as a one-step method to quantify the fitness effects of gene disruptions on a genome-wide scale.

Kingma E, Dolsma F, Inigo de la Cruz L, Laan L PLoS One. 2025; 20(2):e0312437.

PMID: 39913404 PMC: 11801604. DOI: 10.1371/journal.pone.0312437.


Coordination between ESCRT function and Rab conversion during endosome maturation.

Ott D, Desai S, Solinger J, Kaech A, Spang A EMBO J. 2025; .

PMID: 39910226 DOI: 10.1038/s44318-025-00367-7.


References
1.
Huber A, Bodenmiller B, Uotila A, Stahl M, Wanka S, Gerrits B . Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis. Genes Dev. 2009; 23(16):1929-43. PMC: 2725941. DOI: 10.1101/gad.532109. View

2.
Leidel S, Pedrioli P, Bucher T, Brost R, Costanzo M, Schmidt A . Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA. Nature. 2009; 458(7235):228-32. DOI: 10.1038/nature07643. View

3.
Sevier C, Qu H, Heldman N, Gross E, Fass D, Kaiser C . Modulation of cellular disulfide-bond formation and the ER redox environment by feedback regulation of Ero1. Cell. 2007; 129(2):333-44. DOI: 10.1016/j.cell.2007.02.039. View

4.
Mani R, St Onge R, Hartman 4th J, Giaever G, Roth F . Defining genetic interaction. Proc Natl Acad Sci U S A. 2008; 105(9):3461-6. PMC: 2265146. DOI: 10.1073/pnas.0712255105. View

5.
Fong P, Boss D, Yap T, Tutt A, Wu P, Mergui-Roelvink M . Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009; 361(2):123-34. DOI: 10.1056/NEJMoa0900212. View