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

Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.

Wong AS, Choi GC, Cui CH, Pregernig G, Milani P, Adam M, Perli SD, Kazer SW, Gaillard A, Hermann M, Shalek AK, Fraenkel E, Lu TK

The orchestrated action of genes controls complex biological phenotypes, yet the systematic discovery of gene and drug combinations that modulate these phenotypes in human cells is labor intensive and challenging to scale. Here, we created a platform for the massively parallel screening of barcoded combinatorial gene perturbations in human cells and translated these hits into effective drug combinations. This technology ... [more]

Proc. Natl. Acad. Sci. U.S.A. Mar. 01, 2016; 113(9);2544-9 [Pubmed: 26864203]

Throughput

  • High Throughput

Ontology Terms

  • phenotype: growth abnormality (HP:0001507) [ovcar-8/adr cell (BTO:0004189)]

Additional Notes

  • CRISPR GI screen
  • Cell Line: OVCAR-8/ADR cell BTO:0004189
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Identified 61 gene combinations as top hits that resulted in antiproliferative effects (log2 ratio < -0.90) in both biological replicates (Q-value < 0.01).
  • Library: Gecko v2
  • Pooled screen using a GeCKOv2 CRISPR library with barcode abundances compared between day 15 and day 20 groups.
  • Significance Threshold: log2 ratio< -0.90; Q-value< 0.01
  • Used CombiGEM-CRISPR technology to identify gene pairs that inhibited ovarian cancer cell growth (OVCAR8-ADR cells).

Curated By

  • BioGRID