{"doi":"10.1073/pnas.220392197","title":"Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks","abstract":"In an effort to find gene regulatory networks and clusters of genes that affect cancer susceptibility to anticancer agents, we joined a database with baseline expression levels of 7,245 genes measured by using microarrays in 60 cancer cell lines, to a database with the amounts of 5,084 anticancer agents needed to inhibit growth of those same cell lines. Comprehensive pair-wise correlations were calculated between gene expression and measures of agent susceptibility. Associations weaker than a threshold strength were removed, leaving networks of highly correlated genes and agents called relevance networks. Hypotheses for potential single-gene determinants of anticancer agent susceptibility were constructed. The effect of random chance in the large number of calculations performed was empirically determined by repeated random permutation testing; only associations stronger than those seen in multiply permuted data were used in clustering. We discuss the advantages of this methodology over alternative approaches, such as phylogenetic-type tree clustering and self-organizing maps.","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":6020,"datarank":0.9646996622900219,"base_score":6.431331081933479,"endowment":6.431331081933479,"self_citation_contribution":0.9646996622900219,"citation_network_contribution":0.0,"self_endowment_contribution":0.9646996622900219,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":620,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.3531,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2000-10-10","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":32013,"name":"Pablo Tamayo","orcid":"0000-0002-9360-4668","position":1,"is_corresponding":false},{"id":56898,"name":"Donna Slonim","orcid":null,"position":2,"is_corresponding":false},{"id":16671,"name":"Todd R. Golub","orcid":"0000-0003-0113-2403","position":3,"is_corresponding":false},{"id":3527,"name":"Isaac S. Kohane","orcid":"0000-0003-2192-5160","position":4,"is_corresponding":false},{"id":56899,"name":"Donna K. Slonim","orcid":"0000-0003-3357-437X","position":5,"is_corresponding":false},{"id":51,"name":"Atul Janardhan Butte","orcid":"0000-0002-7433-2740","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}