Francisca Vazquez

Abstract Context-dependent synthetic lethality offers a promising strategy for expanding the scope of precision oncology beyond direct oncogene inhibition. We describe various genetic contexts that produce cancer-intrinsic vulnerabilities and consequent synthetic lethal opportunities. We also identify common mechanistic themes that underlie synthetic lethality, such as DNA repair defects, loss of functional redundancies, metabolic imbalances and narrow signalling tolerances.

Abstract Excluding false positives is critical for interpreting CRISPR screens. Here, we introduce a new Chronos module for estimating false discovery rates for identifying knockouts that cause loss of viability or have differential viability effects in different conditions. We introduce a rigorous benchmarking framework using real CRISPR data.