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

Genome-wide CRISPR screens using isogenic cells reveal vulnerabilities conferred by loss of tumor suppressors.

Feng X, Tang M, Dede M, Su D, Pei G, Jiang D, Wang C, Chen Z, Li M, Nie L, Xiong Y, Li S, Park JM, Zhang H, Huang M, Szymonowicz K, Zhao Z, Hart T, Chen J

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide ... [more]

Sci Adv Dec. 13, 2021; 8(19);eabm6638 [Pubmed: 35559673]

Throughput

  • High Throughput

Ontology Terms

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

Additional Notes

  • CRISPR GI screen
  • Cell Line:HEK-293A
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: TKO v3 (ADDGENE:90294)
  • Significance Threshold: BAGEL (QBF_X_TSG KO>5, QBF_X_WT_Average<3, and QBF_X_TSG KO - QBF_X_WT_Max>5, where X is any gene from TKOv3 library) and DrugZ (P<0.01)
  • Significance Threshold: BAGEL (QBF_X_TSG KO>5, QBF_X_WT_Average<3, and QBF_X_TSG KO - QBF_X_WT_Max>5, where X is any gene from TKOv3 library) and DrugZ (P<0.01)

Curated By

  • BioGRID