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Many efforts have been made to detect or predict neurodegenerative disorders, while exploring the pathogenesis has been ignored from a systemic perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To handle this issue, we propose a novel and powerful method, referred to as Pathogenesis-aware Mutual-Assistance Classification and Regression Optimization (Pa-MACRO). First, Pa-MACRO incorporates a mutual-assistance bidirectional mapping technique with a joint-embedding fine-grained interpretability module. This can extract the intrinsic factors and their interactions of multimodal pathogenesis. Second, our method can simultaneously classify an at-risk individual and predict the severity triggered by neurodegenerative disorders. Furthermore, to address the small sample size issue and the high-dimensional issue, we meticulously incorporate a semi-supervised cooperative learning method to integrate unlabeled data and extend it to a chromosome-wide setting in the spirit of divide-and-conquer. The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) database was used to evaluate Pa-MACRO. Without bells and whistles, Pa-MACRO establishes new state-of-the-art results in various settings while maintaining superior interpretability, verifying its power and versatility in revealing the pathogenesis of neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The software is publicly available at https:\/\/github.com\/ZJ-Techie\/Pa-MACRO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf629","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T12:28:17Z","timestamp":1763382497000},"source":"Crossref","is-referenced-by-count":0,"title":["Mutual learning for joint disease detection and severity prediction reveals multimodal pathogenesis for neurodegenerative disorders"],"prefix":"10.1093","volume":"42","author":[{"given":"Jin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Intelligent Science and Technology, Northwestern Polytechnical University , Xi'an, 710072,","place":["China"]}]},{"given":"Yixin","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Nanjing University of Aeronautics and Astronautics , Nanjing, 210000,","place":["China"]}]},{"given":"Jinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"MedVisAl Lab, Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore, 308232,","place":["Singapore"]}]},{"given":"Wenrui","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Intelligent Science and Technology, Northwestern Polytechnical University , Xi'an, 710072,","place":["China"]}]},{"given":"Xiaohui","family":"Yao","sequence":"additional","affiliation":[{"name":"Qingdao Innovation and Development 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