Score ranges
< −1.0
Pan-essentialKnockdown is lethal in nearly all cell lines regardless of tumor type — hallmark of core cellular machinery
−1.0 to −0.5
Strongly essentialStrong growth arrest or lethality in most cancer lines; high-priority therapeutic target
−0.5 to −0.2
Moderately essentialSignificant growth inhibition; effect may be lineage- or mutation-dependent
−0.2 to 0
Weakly / context-dependentMild or variable effect — worthwhile in specific genomic contexts
> 0
DispensableKnockdown tolerated — cells continue growing at normal rate
Sign convention: More negative = more essential. Pan-essential threshold is typically −0.5 in 90%+ of cell lines.
Key concepts
Synthetic lethality
Gene pairs where individual knockdown is tolerated but combined knockdown is lethal. Classical example: BRCA1/2 loss makes cells entirely dependent on PARP for DNA repair — the basis for PARP inhibitor efficacy. Teal chips in gene cards indicate partners also in your panel.
Pan-essential genes
Core cellular machinery (e.g. MYC, CDK1, proteasome subunits). Generally poor drug targets because selective inhibition causes widespread toxicity in normal tissue. Prioritise synthetic lethality strategies for these genes instead.
Context-dependent essentiality
Some genes are essential only in specific lineages or mutation backgrounds (e.g. KRAS in PDAC, EGFR in EGFR-mutant NSCLC). The Disease Context field above biases ranking toward the relevant tumour type.