{"doi":"10.1101/2022.01.10.475617","title":"Pervasive conditional selection of driver mutations and modular epistasis networks in cancer","abstract":"Summary Cancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We developed a method to quantify COnditional SELection on the Excess of Nonsynonymous Substitutions ( Coselens ) in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens , we identified 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario, where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300797,"datarank":0.20975479326422994,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.044962949964013475,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.044962949964013475,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":880027,"name":"George W. Gruenhagen","orcid":"0000-0001-6713-5370","position":1,"is_corresponding":false},{"id":880028,"name":"Jorge Calle-Espinosa","orcid":"0000-0003-2090-2768","position":2,"is_corresponding":false},{"id":17837,"name":"Eugene V. Koonin","orcid":"0000-0003-3943-8299","position":3,"is_corresponding":false},{"id":426016,"name":"Jaime Iranzo","orcid":"0000-0002-4538-7726","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:57.812980Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}