{"doi":"10.1016/j.cell.2023.11.005","title":"Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses","abstract":"Patient-derived organoids (PDOs) can model personalized therapy responses; however, current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly multiplexed mass cytometry platform to measure post-translational modification (PTM) signaling, DNA damage, cell-cycle activity, and apoptosis in >2,500 colorectal cancer (CRC) PDOs and cancer-associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developed \"Trellis\"-a highly scalable, tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is rarer, patient-specific, and aligns with cancer cell PTM signaling. We find that CAFs can regulate PDO plasticity-shifting proliferative colonic stem cells (proCSCs) to slow-cycling revival colonic stem cells (revCSCs) to protect cancer cells from chemotherapy.","journal":"Cell","year":2023,"id":318456,"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":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":566958,"name":"Alexander Tong","orcid":"0000-0002-2031-4096","position":1,"is_corresponding":false},{"id":1025711,"name":"James W. Opzoomer","orcid":"0000-0001-6842-756X","position":2,"is_corresponding":false},{"id":1025712,"name":"Rhianna O’Sullivan","orcid":"0009-0005-6128-7601","position":3,"is_corresponding":false},{"id":1025713,"name":"Ferran Cardoso Rodriguez","orcid":"0000-0002-1376-1242","position":4,"is_corresponding":false},{"id":1025714,"name":"Jahangir Sufi","orcid":"0000-0002-4563-5531","position":5,"is_corresponding":false},{"id":1025715,"name":"Petra Vlckova","orcid":"0000-0001-9633-8492","position":6,"is_corresponding":false},{"id":1025716,"name":"Callum Baird Nattress","orcid":"0000-0001-9326-3632","position":7,"is_corresponding":false},{"id":1025717,"name":"Xiao Qin","orcid":"0000-0002-8738-4187","position":8,"is_corresponding":false},{"id":1025718,"name":"Jeroen Claus","orcid":"0000-0001-9467-955X","position":9,"is_corresponding":false},{"id":620677,"name":"Daniel Hochhauser","orcid":"0000-0001-5522-9281","position":10,"is_corresponding":false},{"id":254926,"name":"Smita Krishnaswamy","orcid":"0000-0001-5823-1985","position":11,"is_corresponding":false},{"id":1025719,"name":"Christopher J. Tape","orcid":"0000-0003-4712-2737","position":12,"is_corresponding":false},{"id":349988,"name":"María Ramos Zapatero","orcid":"0000-0003-3873-5347","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"38065081","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":[]}