{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:10:27Z","timestamp":1759731027626,"version":"3.41.2"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K99CA190910","4R00CA190910-03"],"award-info":[{"award-number":["K99CA190910","4R00CA190910-03"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR001420"],"award-info":[{"award-number":["UL1TR001420"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p>","DOI":"10.1093\/bib\/bbab575","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T20:10:30Z","timestamp":1641327030000},"source":"Crossref","is-referenced-by-count":1,"title":["hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy"],"prefix":"10.1093","volume":"23","author":[{"given":"Yong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, China"},{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"}]},{"given":"Gang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, China"}]},{"given":"Ningbo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, China"}]},{"given":"Kun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, China"}]},{"given":"Wenzhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"given":"Rui-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, China"}]},{"given":"Lingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China"}]},{"given":"Lance D","family":"Miller","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"given":"Timothy","family":"Pardee","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Section of Hematology and Oncology, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, 27157, China"}]},{"given":"Pierre L","family":"Triozzi","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Section of Hematology and Oncology, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, 27157, China"}]},{"given":"Hui-Wen","family":"Lo","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"given":"Kounosuke","family":"Watabe","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"given":"Stephen T C","family":"Wong","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Genome Medicine, Weill Cornell Medicine, Houston Methodist Hospital, Houston, TX 77030, China"}]},{"given":"Boris C","family":"Pasche","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9451-4886","authenticated-orcid":false,"given":"Guangxu","family":"Jin","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, China"},{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, China"}]}],"member":"286","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"2022031506274285000_ref1","doi-asserted-by":"crossref","first-page":"e22153","DOI":"10.1097\/MD.0000000000022153","article-title":"Treatment-related adverse events as surrogate to response rate to immune checkpoint 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