{"doi":"10.1101/2025.05.31.657155","title":"Diverse modes of T cell receptor sequence convergence define unique functional and cellular phenotypes","abstract":"Single-cell techniques allow concurrent study of gene activity and T cell receptor (TCR) sequences, identifying connections between TCR structure and cell traits. Expanding on our CoNGA software, we present a \"metaCoNGA\" analysis of 6 million T cells from 91 diverse studies, mapping TCR sequence similarity across tissues and diseases. This approach exposes shared TCR features within specific T cell subsets, including those associated with infection, cancer, and autoimmunity. We introduce a method to identify T cell groups with similar gene expression and biased TCR amino acid composition, providing a systematic framework for classifying diverse unconventional T cells, including KIR+ CD8+ T cells, CD4+ regulatory T cells, and subsets of NKT and MAIT cells. A new TCR clustering approach identifies thousands of convergent TCR sequence clusters hypothesized to target shared antigens. These clusters show coherent gene expression, highlighting the role of antigen exposure in shaping T cell behavior. Finally, we provide a tool for users to merge new data with this resource and rapidly identify T cell features in their data sets. This resource empowers investigations into the complex relationship between TCR sequence and T cell function in human health.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556402,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9291,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1025844,"name":"Kasi Vegesana","orcid":"0000-0001-8847-3774","position":1,"is_corresponding":false},{"id":597510,"name":"William D. Hazelton","orcid":"0000-0002-7975-5080","position":2,"is_corresponding":false},{"id":618932,"name":"Anastasia A. Minervina","orcid":"0000-0001-9884-6351","position":3,"is_corresponding":false},{"id":1455655,"name":"Sebastiaan Valkiers","orcid":"0000-0002-4940-1310","position":4,"is_corresponding":false},{"id":55718,"name":"Kamil Slowikowski","orcid":"0000-0002-2843-6370","position":5,"is_corresponding":false},{"id":89090,"name":"Neal P. Smith","orcid":"0000-0003-1394-3158","position":6,"is_corresponding":false},{"id":1456066,"name":"MGH COVID-19 Team","orcid":null,"position":7,"is_corresponding":false},{"id":14837,"name":"Alexandra–Chloé Villani","orcid":"0000-0001-7461-0408","position":8,"is_corresponding":false},{"id":225737,"name":"Paul G. Thomas","orcid":"0000-0001-7955-0256","position":9,"is_corresponding":false},{"id":114739,"name":"Philip Bradley","orcid":"0000-0002-0224-6464","position":10,"is_corresponding":false},{"id":556317,"name":"Stefan Schattgen","orcid":"0000-0002-6860-5079","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:55:08.896385Z","pmid":"40501778","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":[]}