{"doi":"10.1016/j.ccell.2023.12.016","title":"A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization","abstract":"Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens. We identify dependency-associated gene expression markers beyond driver genes, and observe many gene addiction relationships driven by gain of function rather than synthetic lethal effects. By combining clinically informed dependency-marker associations with protein-protein interaction networks, we identify 370 anti-cancer priority targets for 27 cancer types, many of which have network-based evidence of a functional link with a marker in a cancer type. Mapping these targets to sequenced tumor cohorts identifies tractable targets in different cancer types. This target prioritization map enhances understanding of gene dependencies and identifies candidate anti-cancer targets for drug development.","journal":"Cancer Cell","year":2024,"id":416836,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":96,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":85479,"name":"Emma L. 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Behan","orcid":"0000-0002-9070-7688","position":13,"is_corresponding":false},{"id":628835,"name":"Lykourgos‐Panagiotis Zalmas","orcid":"0000-0002-4317-7709","position":14,"is_corresponding":false},{"id":1202045,"name":"Andrew Barthorpe","orcid":null,"position":15,"is_corresponding":false},{"id":1202046,"name":"Hayley E. Francies","orcid":null,"position":16,"is_corresponding":false},{"id":1202047,"name":"Steve Rowley","orcid":null,"position":17,"is_corresponding":false},{"id":34984,"name":"Jack Pollard","orcid":"0000-0003-0100-5412","position":18,"is_corresponding":false},{"id":1495,"name":"Pedro Beltrão","orcid":"0000-0002-2724-7703","position":19,"is_corresponding":false},{"id":17368,"name":"Leopold Parts","orcid":"0000-0002-2618-670X","position":20,"is_corresponding":false},{"id":843541,"name":"Francesco Iorio","orcid":"0000-0001-7063-8913","position":21,"is_corresponding":false},{"id":12559,"name":"Mathew J. 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