Comprehensively charting the biologically causal circuits that govern the phenotypic space
of human cells has often been viewed as an insurmountable challenge. However, in the last …

The accurate and complete replication of genomic DNA is essential for all life. In eukaryotic
cells, the assembly of the multi-enzyme replisomes that perform replication is divided into …

Genetic robustness, or the ability of an organism to maintain fitness in the presence of
harmful mutations, can be achieved via protein feedback loops. Previous work has …

Seminal yeast studies have established the value of comprehensively map** genetic
interactions (GIs) for inferring gene function. Efforts in human cells using focused gene sets …

We developed a systematic approach to map human genetic networks by combinatorial
CRISPR–Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all …

Hunger is a complex behavioural state that elicits intense food seeking and consumption.
These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP …

The concept of synthetic lethality has been widely applied to identify therapeutic targets in
cancer, with varying degrees of success. The standard approach normally involves …

Identification of effective combination therapies is critical to address the emergence of drug-
resistant cancers, but direct screening of all possible drug combinations is infeasible. Here …

A central goal of systems biology is to elucidate the structural and functional architecture of
the cell. To this end, large and complex networks of molecular interactions are being rapidly …

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