{"doi":"10.1093/bib/bbab575","title":"hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy","abstract":"There is a lack of robust generalizable predictive biomarkers of response to immune checkpoint blockade in multiple types of cancer. We develop hDirect-MAP, an algorithm that maps T cells into a shared high-dimensional (HD) expression space of diverse T cell functional signatures in which cells group by the common T cell phenotypes rather than dimensional reduced features or a distorted view of these features. Using projection-free single-cell modeling, hDirect-MAP first removed a large group of cells that did not contribute to response and then clearly distinguished T cells into response-specific subpopulations that were defined by critical T cell functional markers of strong differential expression patterns. We found that these grouped cells cannot be distinguished by dimensional-reduction algorithms but are blended by diluted expression patterns. Moreover, these identified response-specific T cell subpopulations enabled a generalizable prediction by their HD metrics. Tested using five single-cell RNA-seq or mass cytometry datasets from basal cell carcinoma, squamous cell carcinoma and melanoma, hDirect-MAP demonstrated common response-specific T cell phenotypes that defined a generalizable and accurate predictive biomarker.","journal":"Briefings in Bioinformatics","year":2022,"id":293540,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":978261,"name":"Gang Xue","orcid":"0000-0002-4116-5819","position":1,"is_corresponding":false},{"id":978262,"name":"Ningbo Zheng","orcid":"0000-0002-3684-5596","position":2,"is_corresponding":false},{"id":633101,"name":"Kun Han","orcid":"0000-0003-0235-2301","position":3,"is_corresponding":false},{"id":287262,"name":"Wenzhong Yang","orcid":null,"position":4,"is_corresponding":false},{"id":584374,"name":"Rui‐Sheng Wang","orcid":"0000-0003-4920-4357","position":5,"is_corresponding":false},{"id":978263,"name":"Ling‐Yun Wu","orcid":"0000-0001-9487-0215","position":6,"is_corresponding":false},{"id":173915,"name":"Lance D. Miller","orcid":"0000-0003-3799-2528","position":7,"is_corresponding":false},{"id":305981,"name":"Timothy S. Pardee","orcid":"0000-0002-1186-6948","position":8,"is_corresponding":false},{"id":818233,"name":"Pierre L. Triozzi","orcid":"0000-0003-2488-6136","position":9,"is_corresponding":false},{"id":347638,"name":"Hui‐Wen Lo","orcid":"0000-0002-0681-7914","position":10,"is_corresponding":false},{"id":274312,"name":"Kounosuke Watabe","orcid":"0000-0001-7441-6322","position":11,"is_corresponding":false},{"id":97864,"name":"Stephen T.C. Wong","orcid":"0000-0001-9188-6502","position":12,"is_corresponding":false},{"id":288151,"name":"Boris Pasche","orcid":"0000-0002-3750-7898","position":13,"is_corresponding":false},{"id":288152,"name":"Wei Zhang","orcid":"0000-0002-2235-1851","position":14,"is_corresponding":false},{"id":673492,"name":"Guangxu Jin","orcid":"0000-0001-9451-4886","position":15,"is_corresponding":false},{"id":553821,"name":"Yong Lu","orcid":"0000-0003-0077-0040","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:30:53.818562Z","pmid":"35037026","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":[]}