Exploring genetic interaction manifolds constructed from rich single-cell phenotypes

Manifold destiny Mapping of genetic interactions (GIs) is usually based on cell fitness as the phenotypic readout, which obscures the mechanistic origin of interactions. Norman et al. developed a framework for mapping and understanding GIs. This approach leverages high-dimensional single-cell RNA sequencing data gathered from CRISPR-mediated, pooled perturbation screens. Diverse transcriptomic phenotypes construct a “manifold” representing all possible states of the cell. Each perturbation and GI projects the cell state to a particular position on this manifold, enabling unbiased ordering of genes in pathways and systematic classifications of GIs. Science , this issue p. 786