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This identification is critical for developing vaccines and cancer immunotherapies. Current prediction methods are limited, primarily due to a lack of high-quality training epitope datasets and algorithmic constraints. To predict the exogenous HLA class II-restricted peptides across most of the human population, we utilized the mass spectrometry data to profile &amp;gt;223 000 eluted ligands over HLA-DR, -DQ, and -DP alleles. Here, by integrating these data with peptide processing and gene expression, we introduce HLAIImaster, an attention-based deep learning framework with adaptive domain knowledge for predicting neoepitope immunogenicity. Leveraging diverse biological characteristics and our enhanced deep learning framework, HLAIImaster is significantly improved against existing tools in terms of positive predictive value across various neoantigen studies. Robust domain knowledge learning accurately identifies neoepitope immunogenicity, bridging the gap between neoantigen biology and the clinical setting and paving the way for future neoantigen-based therapies to provide greater clinical benefit. In summary, we present a comprehensive exploitation of the immunogenic neoepitope repertoire of cancers, facilitating the effective development of \u201cjust-in-time\u201d personalized vaccines.<\/jats:p>","DOI":"10.1093\/bib\/bbae302","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T11:43:57Z","timestamp":1719402237000},"source":"Crossref","is-referenced-by-count":18,"title":["HLAIImaster: a deep learning method with adaptive domain knowledge predicts HLA II neoepitope immunogenic responses"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-9443","authenticated-orcid":false,"given":"Qiang","family":"Yang","sequence":"first","affiliation":[{"name":"School of Medicine and Health, Harbin Institute of Technology , Yikuang Street, Harbin 150000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-9178","authenticated-orcid":false,"given":"Long","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , West Dazhi Street, Harbin 150001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8022-9793","authenticated-orcid":false,"given":"Weihe","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , Hexing Road, Harbin 150004 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-6890","authenticated-orcid":false,"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , West Dazhi Street, Harbin 150001 , China"},{"name":"School of Computer Science and Technology, Heilongjiang University , Xuefu Road, Harbin 150080 , China"},{"name":"Postdoctoral Program of Heilongjiang Hengxun Technology Co., Ltd. , Xuefu Road, Harbin 150090 , China"},{"name":"Shandong Hengxun Technology Co., Ltd. , Miaoling Road, Qingdao 266100 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-3491","authenticated-orcid":false,"given":"Kuanquan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , West Dazhi Street, Harbin 150001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-8782","authenticated-orcid":false,"given":"Suyu","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , Hexing Road, Harbin 150004 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-2361","authenticated-orcid":false,"given":"Xianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Harbin Medical University Cancer Hospital , Haping Road, Harbin 150081 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiansong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, and Traditional Chinese Medicine Informatics Key Laboratory of Heilongjiang Province , Heping Road, Harbin 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine and Health, Harbin Institute of Technology , Yikuang Street, Harbin 150000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8835-8370","authenticated-orcid":false,"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Computer , Electrical and Mathematical Sciences & Engineering Division, , 4700 KAUST, Thuwal 23955 , Saudi Arabia"},{"name":"King Abdullah University of Science and Technology , Electrical and Mathematical Sciences & Engineering Division, , 4700 KAUST, Thuwal 23955 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-0335","authenticated-orcid":false,"given":"Gongning","family":"Luo","sequence":"additional","affiliation":[{"name":"Computer , Electrical and Mathematical Sciences & Engineering Division, , 4700 KAUST, Thuwal 23955 , Saudi Arabia"},{"name":"King Abdullah University of Science and Technology , Electrical and Mathematical Sciences & Engineering Division, , 4700 KAUST, Thuwal 23955 , Saudi 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