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

Combinatorial CRISPR screen identifies fitness effects of gene paralogues.

Thompson NA, Ranzani M, van der Weyden L, Iyer V, Offord V, Droop A, Behan F, Goncalves E, Speak A, Iorio F, Hewinson J, Harle V, Robertson H, Anderson E, Fu B, Yang F, Zagnoli-Vieira G, Chapman P, Del Castillo Velasco-Herrera M, Garnett MJ, Jackson SP, Adams DJ

Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose ... [more]

Nat Commun Dec. 26, 2020; 12(1);1302 [Pubmed: 33637726]

Throughput

  • Low Throughput

Ontology Terms

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

Additional Notes

  • CRISPR GI screen
  • Cell Line: RPE-1
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: Targeted CRISPR synthetic lethality library
  • Significance Threshold:FDR<0.1 and additional filtering of gene pairs with one gene with a large individual fitness defect

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
ARFGEF1 ARFGEF2
Affinity Capture-MS
Affinity Capture-MS

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner is identified by mass spectrometric methods.

High-BioGRID
3347934
ARFGEF2 ARFGEF1
Affinity Capture-MS
Affinity Capture-MS

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner is identified by mass spectrometric methods.

High-BioGRID
3347940
ARFGEF1 ARFGEF2
Affinity Capture-Western
Affinity Capture-Western

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner identified by Western blot with a specific polyclonal antibody or second epitope tag. This category is also used if an interacting protein is visualized directly by dye stain or radioactivity. Note that this differs from any co-purification experiment involving affinity capture in that the co-purification experiment involves at least one extra purification step to get rid of potential contaminating proteins.

Low-BioGRID
-
ARFGEF2 ARFGEF1
Affinity Capture-Western
Affinity Capture-Western

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner identified by Western blot with a specific polyclonal antibody or second epitope tag. This category is also used if an interacting protein is visualized directly by dye stain or radioactivity. Note that this differs from any co-purification experiment involving affinity capture in that the co-purification experiment involves at least one extra purification step to get rid of potential contaminating proteins.

Low-BioGRID
-
ARFGEF1 ARFGEF2
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.

Low-BioGRID
-
ARFGEF1 ARFGEF2
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
-

Curated By

  • BioGRID