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

  • 0.001405036 [Confidence Score]

Throughput

  • High Throughput

Additional Notes

  • CRISPR GI screen
  • Cell Line: IPC298_SKIN score (0.0014050356304632)
  • Experimental Setup: Timecourse-Synthetic Lethality
  • GIST: A-phenotypic negative genetic interaction
  • Library: Digenic Paralog CRISPR library
  • Significance Threshold: GEMINI FDR < 0.05

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
AP2A1 AP2A2
Co-fractionation
Co-fractionation

Interaction inferred from the presence of two or more protein subunits in a partially purified protein preparation. If co-fractionation is demonstrated between 3 or more proteins, then add them as a complex.

High0.836BioGRID
744619
AP2A2 AP2A1
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
3720111
AP2A1 AP2A2
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
-
AP2A2 AP2A1
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
3745327
AP2A2 AP2A1
Negative Genetic
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.

Low-BioGRID
3411596

Curated By

  • BioGRID