Gene

Quantum mechanics

Engineering

Biology

Theoretical computer science

Perturbation (astronomy)

Computer science

Destiny (ISS module)

Computational biology

Evolutionary biology

Mechanical engineering

Genetics

Physics

Mathematics

Astronomy

Combinatorics

Cell

Topology (electrical circuits)

Manifold (fluid mechanics)

Phenotype

Science

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

Exploring genetic interaction manifolds constructed from rich single-cell phenotypes