Negative Genetic

Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. This term is reserved for high or low throughput studies with scores.

Publication

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

Shen JP, Zhao D, Sasik R, Luebeck J, Birmingham A, Bojorquez-Gomez A, Licon K, Klepper K, Pekin D, Beckett AN, Sanchez KS, Thomas A, Kuo CC, Du D, Roguev A, Lewis NE, Chang AN, Kreisberg JF, Krogan N, Qi L, Ideker T, Mali P

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 pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these ... [more]

Nat. Methods Mar. 20, 2017; 0(); [Pubmed: 28319113]

Throughput

  • High Throughput

Ontology Terms

  • phenotype: hek-293t cell (BTO:0002181)
  • phenotype: viability (PATO:0000169)
  • phenotype: growth abnormality (HP:0001507)
  • phenotype: a-549 cell (BTO:0000018)

Additional Notes

  • CRISPR GI screen
  • Cell Line: A-549 EFO:0001086/HEK293T EFO:0001184
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: Dual-guide CRISPRn library
  • Significance Threshold:FDR ~ 0.3

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
IGF1R PRKDC
Affinity Capture-MS
Affinity Capture-MS

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner is identified by mass spectrometric methods.

High0BioGRID
3504952
IGF1R PRKDC
Proximity Label-MS
Proximity Label-MS

An interaction is inferred when a bait-enzyme fusion protein selectively modifies a vicinal protein with a diffusible reactive product, followed by affinity capture of the modified protein and identification by mass spectrometric methods.

High0.02BioGRID
3505182

Curated By

  • BioGRID