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

Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer.

Vichas A, Riley AK, Nkinsi NT, Kamlapurkar S, Parrish PCR, Lo A, Duke F, Chen J, Fung I, Watson J, Rees M, Gabel AM, Thomas JD, Bradley RK, Lee JK, Hatch EM, Baine MK, Rekhtman N, Ladanyi M, Piccioni F, Berger AH

CRISPR-based cancer dependency maps are accelerating advances in cancer precision medicine, but adequate functional maps are limited to the most common oncogenes. To identify opportunities for therapeutic intervention in other rarer subsets of cancer, we investigate the oncogene-specific dependencies conferred by the lung cancer oncogene, RIT1. Here, genome-wide CRISPR screening in KRAS, EGFR, and RIT1-mutant isogenic lung cancer cells identifies ... [more]

Nat Commun Dec. 09, 2020; 12(1);4789 [Pubmed: 34373451]

Throughput

  • High Throughput

Ontology Terms

  • growth abnormality (HP:0001507) [viability (PATO:0000169)]

Additional Notes

  • CRISPR GI screen
  • Cell Line: PC9-Cas9-RIT1M90I
  • Experimental Setup: Negative selection in the presence of 40 nM erlotinib
  • GIST: A-phenotypic negative genetic interaction
  • Library: Brunello Library
  • Significance Threshold:
  • CS
  • >0.5 and p<0.05

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
ATP6V1B2 RIT1
Cross-Linking-MS (XL-MS)
Cross-Linking-MS (XL-MS)

An interaction is detected between two proteins using chemically reactive or photo-activatable cross-linking reagents that covalently link amino acids in close proximity, followed by mass spectrometry analysis to identify the linked peptides (reviewed in PMID 37406423, 37104977). Experiments may be carried with live cells or cell lysates in which all proteins are expressed at endogenous levels (e.g. PMID 34349018, 35235311) or with recombinant proteins (e.g., PMID 28537071).

High-BioGRID
3793112

Curated By

  • BioGRID