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: a-549 cell (BTO:0000018)
  • phenotype: growth abnormality (HP:0001507)
  • phenotype: viability (PATO:0000169)
  • phenotype: hela cell (BTO:0000567)

Additional Notes

  • CRISPR GI screen
  • Cell Line: A-549 EFO:0001086/HeLa EFO:0001185
  • 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
PRKDC CHEK1
Protein-peptide
Protein-peptide

An interaction is detected between a protein and a peptide derived from an interaction partner. This includes phage display experiments.

Low-BioGRID
245123
CHEK1 PRKDC
Reconstituted Complex
Reconstituted Complex

An interaction is inferred between proteins in vitro. This can include proteins in recombinant form or proteins isolated directly from cells with recombinant or purified bait. For example, GST pull-down assays where a GST-tagged protein is first isolated and then used to fish interactors from cell lysates are considered reconstituted complexes (e.g. PUBMED: 14657240, Fig. 4A or PUBMED: 14761940, Fig. 5). This can also include gel-shifts, surface plasmon resonance, isothermal titration calorimetry (ITC) and bio-layer interferometry (BLI) experiments. The bait-hit directionality may not be clear for 2 interacting proteins. In these cases the directionality is up to the discretion of the curator.

Low-BioGRID
-

Curated By

  • BioGRID