Global Genetic Networks and the Genotype-to-Phenotype Relationship

Pioneering yeast genetic interaction maps between all gene pairs enabled systematic determination of gene function, identification of protein complexes, and definition of gene regulatory networks.

“Pioneering efforts in yeast to construct systematic GI maps between all gene pairs have enabled systematic determination of gene function, identification of protein complexes and definition of gene regulatory networks in a principled and unbiased manner (1, 2).”

Genes that exhibit phenotypes when expressed alone have a higher rate of genetic interactions with other genes.

“Genes that exhibit phenotypes when expressed alone have a higher rate of genetic interactions with other genes (1, 2).”

The structure of the CRISPRa genetic interaction map, like past loss-of-function maps, can assign function to individual genes by similarity of genetic interaction profiles.

“Thus the structure of the CRISPRa GI map, like past efforts based on loss-of-function alleles, can assign function to individual genes by the similarity of GI profiles (1, 2).”

Functionally related genes interact similarly, making the genetic interaction manifold highly constrained and enabling imputation strategies.

“We and others have established that functionally related genes interact similarly—in geometric terms the GI manifold is therefore highly constrained, enabling imputation strategies (1, 2, 7, 12, 29).”

Costanzo et al. assembled a hierarchy of biological processes using data from a large-scale screen of genetic interactions that examined cell growth for most double mutants of yeast genes, identifying about one million genetic interactions.

“As another example, Costanzo et al. assembled a hierarchy of biological processes using data from a large scale screen of genetic interactions, which examined cell growth for most double mutants of yeast genes, identifying ~1 million genetic interactions (Costanzo et al., 2016, 2019).”