{"doi":"10.1016/j.isci.2024.109752","title":"Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in triple negative breast cancer","abstract":"Breast cancers (BRCA) exhibit substantial transcriptional heterogeneity, posing a significant clinical challenge. The global transcriptional changes in a disease context, however, are likely mediated by few key genes which reflect disease etiology better than the differentially expressed genes (DEGs). We apply our network-based tool PathExt to 1,059 BRCA tumors across 4 subtypes to identify key mediator genes in each subtype. Compared to conventional differential expression analysis, PathExt-identified genes exhibit greater concordance across tumors, revealing shared and subtype-specific biological processes; better recapitulate BRCA-associated genes in multiple benchmarks, and are more essential in BRCA subtype-specific cell lines. Single-cell transcriptomic analysis reveals a subtype-specific distribution of PathExt-identified genes in multiple cell types from the tumor microenvironment. Application of PathExt to a TNBC chemotherapy response dataset identified subtype-specific key genes and biological processes associated with resistance. We described putative drugs that target key genes potentially mediating drug resistance.","journal":"iScience","year":2024,"id":440148,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9371,"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":778903,"name":"Navami Jain","orcid":null,"position":1,"is_corresponding":false},{"id":300502,"name":"Vishaka Gopalan","orcid":null,"position":2,"is_corresponding":false},{"id":1186726,"name":"Annan Timon","orcid":null,"position":3,"is_corresponding":false},{"id":714145,"name":"Arashdeep Singh","orcid":"0000-0001-6087-7240","position":4,"is_corresponding":false},{"id":264323,"name":"Padma Sheila Rajagopal","orcid":"0000-0002-0489-0819","position":5,"is_corresponding":false},{"id":4087,"name":"Sridhar Hannenhalli","orcid":"0000-0001-9603-7569","position":6,"is_corresponding":false},{"id":483546,"name":"Piyush Agrawal","orcid":"0000-0003-2075-1111","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:00:57.233748Z","pmid":"38699227","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":[]}