{"doi":"10.1093/bib/bbad220","title":"Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing","abstract":"The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.","journal":"Briefings in Bioinformatics","year":2023,"id":337334,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"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":378458,"name":"Theodore S. Nowicki","orcid":"0000-0002-3815-6137","position":1,"is_corresponding":false},{"id":226341,"name":"Katie M. Campbell","orcid":"0000-0001-6491-4432","position":2,"is_corresponding":false},{"id":827256,"name":"Mohammad Vahed","orcid":"0000-0002-4721-2356","position":3,"is_corresponding":false},{"id":994982,"name":"Dandan Peng","orcid":"0000-0003-2006-0804","position":4,"is_corresponding":false},{"id":1068677,"name":"Yiting Meng","orcid":"0000-0002-3747-116X","position":5,"is_corresponding":false},{"id":994983,"name":"Anish Nagareddy","orcid":"0000-0002-5835-4165","position":6,"is_corresponding":false},{"id":32449,"name":"Yu-Ning Huang","orcid":"0000-0003-1697-4267","position":7,"is_corresponding":false},{"id":346601,"name":"Aaron Karlsberg","orcid":null,"position":8,"is_corresponding":false},{"id":400493,"name":"Zachary M. Miller","orcid":"0000-0002-6737-7625","position":9,"is_corresponding":false},{"id":345397,"name":"Jaqueline Brito","orcid":"0000-0002-7158-3253","position":10,"is_corresponding":false},{"id":110471,"name":"Brian B. Nadel","orcid":"0000-0002-9583-8169","position":11,"is_corresponding":false},{"id":62297,"name":"Victoria M. Pak","orcid":"0000-0002-4081-8347","position":12,"is_corresponding":false},{"id":32464,"name":"Malak Abedalthagafi","orcid":"0000-0003-1786-3366","position":13,"is_corresponding":false},{"id":528447,"name":"Amanda M. Burkhardt","orcid":"0000-0002-7326-474X","position":14,"is_corresponding":false},{"id":497048,"name":"Houda Alachkar","orcid":"0000-0001-5567-5521","position":15,"is_corresponding":false},{"id":58599,"name":"Antoni Ribas","orcid":"0000-0003-3669-8458","position":16,"is_corresponding":false},{"id":6600,"name":"Serghei Mangul","orcid":"0000-0003-4770-3443","position":17,"is_corresponding":false},{"id":645145,"name":"Kerui Peng","orcid":"0000-0002-9362-4618","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:10:26.690308Z","pmid":"37291798","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":[]}