ArticleGenome biology2023
Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 32 citations in OpenAlex.
- Article
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- Transcriptomic profiling of epigenetic regulators and metabolic reprogramming in human cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Article
- An enzymatic cascade enables sensitive and specific proximity labeling proteomics in challenging biological systems.Nature communications · 2025Article
- Identification of Anticancer Targets in Ovarian Cancer Using Genomic Drug Sensitivity Data.International journal of molecular sciences · 2025Article
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- Generation of a Biliary Tract Cancer Cell Line Atlas Identifies Molecular Subtypes and Therapeutic Targets.Cancer discovery · 2025Article
- Exon inclusion signatures enable accurate estimation of splicing factor activity.bioRxiv : the preprint server for biology · 2025Article
- A side-by-side comparison of variant function measurements using deep mutational scanning and base editing.Nucleic acids research · 2025Article
- Suppression of NRAS-mutant melanoma growth with NRAS-targeting Antisense Oligonucleotide treatment reveals therapeutically relevant kinase co-dependencies.Communications medicine · 2025Article
- Article
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications.Nature communications · 2024Article
- Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx.Nature methods · 2024Article
- Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.The EMBO journal · 2024Article
- Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.Nature communications · 2024Article
- Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry.European journal of medical research · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHundreds of functional genomic screens have been performed across a diverse set of cancer contexts, as part of efforts such as the Cancer Dependency Map, to identify gene dependencies-genes whose loss of function reduces cell viability or fitness. Recently, large-scale screening efforts have shifted from RNAi to CRISPR-Cas9, due to superior efficacy and specificity. However, many effective oncology drugs only partially inhibit their protein targets, leading us to question whether partial suppression of genes using RNAi could reveal cancer vulnerabilities that are missed by complete knockout using CRISPR-Cas9. Here, we compare CRISPR-Cas9 and RNAi dependency profiles of genes across approximately 400 matched cancer cell lines.
resultsWe find that CRISPR screens accurately identify more gene dependencies per cell line, but the majority of each cell line's dependencies are part of a set of 1867 genes that are shared dependencies across the entire collection (pan-lethals). While RNAi knockdown of about 30% of these genes is also pan-lethal, approximately 50% have selective dependency patterns across cell lines, suggesting they could still be cancer vulnerabilities. The accuracy of the unique RNAi selectivity is supported by associations to multi-omics profiles, drug sensitivity, and other expected co-dependencies.
conclusionsIncorporating RNAi data for genes that are pan-lethal knockouts facilitates the discovery of a wider range of gene targets than could be detected using the CRISPR dataset alone. This can aid in the interpretation of contrasting results obtained from CRISPR and RNAi screens and reinforce the importance of partial gene suppression methods in building a cancer dependency map.
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