{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:45:59Z","timestamp":1780058759230,"version":"3.54.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62302215"],"award-info":[{"award-number":["62302215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Fellowship Program of CPSF","award":["GZC20233494"],"award-info":[{"award-number":["GZC20233494"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>With the increasing number of indications for immune checkpoint inhibitors in early and advanced cancers, the prospect of a tumor-agnostic biomarker to prioritize patients is compelling. Tumor mutation burden (TMB) is a widely endorsed biomarker that quantifies nonsynonymous mutations within tumor DNA, essential for neoantigen production, which, in turn, correlates with the immune response and guides decision-making. However, the general clinical application of TMB\u2014relying on simple mutational counts targeted at a single endpoint\u2014does not adequately capture the complex clonal structure of tumors nor the multifaceted nature of prognostic indicators. This recognition has spurred the exploration of sophisticated high-dimensional regression techniques. Unfortunately, the limited cohort sizes in immunotherapy trials have hindered the full potential of these advanced methods. Our approach considers patient subgroups as related yet distinct entities, enabling precise tailoring and refinement to address subgroup-specific dynamics. Given the deficiencies and the constraints, we introduce a TMB heterogeneity-optimized regression (THOR). This innovative model enhances the predictive capabilities of TMB by integrating tumor clonality and a diverse spectrum of clinical endpoints, further augmented by fusion techniques across subgroups to facilitate robust data sharing and interpretation. Our simulations validate THOR\u2019s superiority in parameter estimation for statistical inference. Clinically, we assess the utility of THOR in a structured cohort of 238 cancer patients undergoing immunotherapy, supplemented by 2212 patients across 19 subgroups from public datasets. The forecast of the responses and comparison of survival hazards demonstrate that THOR significantly enhances patient stratification and prognostic predictions by incorporating complex immunogenetic biology and subgroup-specific dynamics.<\/jats:p>","DOI":"10.1093\/bib\/bbae648","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T10:36:58Z","timestamp":1734345418000},"source":"Crossref","is-referenced-by-count":6,"title":["THOR: a TMB heterogeneity-adaptive optimization model predicts immunotherapy response using clonal genomic features in group-structured data"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-1769","authenticated-orcid":false,"given":"Yixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]},{"name":"Nanjing University of Aeronautics and Astronautics , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Guan","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Xi\u2019an Jiaotong University , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Geneplus-Beijing Institute , 8 Life Park Road, Changping, Beijing 102206,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Xi\u2019an Jiaotong University , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Xi\u2019an Jiaotong University , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Xi\u2019an Jiaotong University , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Geneseeq Research Institute, Nanjing Geneseeq Technology Inc. , 128 Huakang Road, Pukou, Nanjing 210032,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Xi\u2019an Jiaotong University , Faculty of Electronics and Information Engineering, , 28 Xianning West Road, Beilin, Xi\u2019an 710049,","place":["China"]},{"name":"Geneseeq Research Institute, Nanjing Geneseeq Technology Inc. , 128 Huakang Road, Pukou, Nanjing 210032,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]},{"name":"Nanjing University of Aeronautics and Astronautics , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]},{"name":"Nanjing University of Aeronautics and Astronautics , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]},{"name":"Nanjing University of Aeronautics and Astronautics , College of Automation Engineering, , 29 Jiangjun Avenue, Jiangning, Nanjing 211106,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , 3 Shangqin Road, Xincheng, Xi\u2019an 710004,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology , Faculty of Electronics and 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