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

Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers.

Ito T, Young MJ, Li R, Jain S, Wernitznig A, Krill-Burger JM, Lemke CT, Monducci D, Rodriguez DJ, Chang L, Dutta S, Pal D, Paolella BR, Rothberg MV, Root DE, Johannessen CM, Parida L, Getz G, Vazquez F, Doench JG, Zamanighomi M, Sellers WR

Although single-gene perturbation screens have revealed a number of new targets, vulnerabilities specific to frequently altered drivers have not been uncovered. An important question is whether the compensatory relationship between functionally redundant genes masks potential therapeutic targets in single-gene perturbation studies. To identify digenic dependencies, we developed a CRISPR paralog targeting library to investigate the viability effects of disrupting 3,284 ... [more]

Nat Genet Dec. 01, 2021; 53(12);1664-1672 [Pubmed: 34857952]

Quantitative Score

  • 0.007089196 [Confidence Score]

Throughput

  • High Throughput

Additional Notes

  • CRISPR GI screen
  • Cell Line: A549_LUNG score (0.0070891962702983)
  • Cell Line: HSC5_SKIN score (0.0032825136712831)
  • Cell Line: IPC298_SKIN score (0.0014487898478886)
  • Experimental Setup: Timecourse-Synthetic Lethality
  • GIST: A-phenotypic negative genetic interaction
  • Library: Digenic Paralog CRISPR library
  • Significance Threshold: GEMINI FDR < 0.05

Curated By

  • BioGRID