Human Gene Set: GENES_CORRELATED_WITH_DOT1L_DELETION


Standard name GENES_CORRELATED_WITH_DOT1L_DELETION
Systematic name M50985
Brief description Genes correlated with the sensitivity to CRISPR knockdown of gene DOT1L [GeneSymbol=DOT1L]
Full description or abstract The procedure to generate this gene set is as follows: we began by generating a CRISPR sensitivity vector using the negative relative cell viability readouts from the DepMap CRISPR screen (release 25Q3, Broad Institute) for gene DOT1L. We aligned this dependency data with DepMap global mRNA expression data (CCLE mRNA, release 25Q3), retaining only the 1,106 cell lines present in both datasets. The overlapping samples were randomly partitioned into a Training Set (66%) and a Test Set (34%). Using an information-theoretic association metric, we quantified the association between the CRISPR dependency target and the mRNA expression of every gene in the training set. This process ranked genes based on how closely their expression aligned with the specific gene DOT1L CRISPR dependency. Subsequently, we performed a gene set optimization procedure. Using varying numbers of the top-ranked genes we constructed candidate gene signatures. We then computed the association of their ssGSEA-derived enrichment scores against the CRISPR target, and identified the gene set size that maximized the association score in the training data. This procedure defined the final genetic perturbation-based gene set for gene DOT1L. Finally, we validated the gene set against the target in the test set to ensure it exceeded a minimum association threshold (0.20).
Collection C9: Computational Perturbation Signature
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Source species Homo sapiens
Contributed by Pablo Tamayo (MSigDB Team)
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Version history 2026.1.Hs: First Introduced.


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