The role of epistasis in the genetic architecture of quantitative traits is controversial, despite
the biological plausibility that nonlinear molecular interactions underpin the genotype …

Despite considerable progress in genome-and proteome-based high-throughput screening
methods and in rational drug design, the increase in approved drugs in the past decade did …

INTRODUCTION Genetic interactions occur when mutations in two or more genes combine
to generate an unexpected phenotype. An extreme negative or synthetic lethal genetic …

Genetic interactions identify combinations of genetic variants that impinge on phenotype.
With whole-genome sequence information available for thousands of individuals within a …

Network “guilt by association”(GBA) is a proven approach for identifying novel disease
genes based on the observation that similar mutational phenotypes arise from functionally …

Despite advances in high-throughput sequencing that have revolutionized the discovery of
gene defects in rare Mendelian diseases, there are still gaps in translating individual …

Synthetic lethality occurs when the inhibition of two genes is lethal while the inhibition of
each single gene is not. It can be harnessed to selectively treat cancer by identifying inactive …

Synthetic lethality occurs when the simultaneous perturbation of two genes results in cellular
or organismal death. Synthetic lethality also occurs between genes and small molecules …

In any given cell, thousands of genes are expressed and work in concert to ensure the cell's
function, fitness, and survival. Each gene, in turn, must be expressed at the proper time and …

The remarkable gene knockdown technique of RNAi has opened exciting new avenues for
genetic screens in model organisms and human cells. Here we describe the current state of …