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We present MVGCL, a type-aware dual-pathway framework that combines noise-robust multisource similarity fusion with heterogeneous biological network representation learning and aligns the two pathways through a distribution-aware hierarchical contrastive strategy to improve representation consistency under sparse and noisy supervision. Under 10-fold cross-validation protocols consistent with prior work, MVGCL achieves the highest AUC and AUPR on all three benchmark data sets, reaching 0.9538\/0.9511 on B-data set, 0.9871\/0.9890 on C-data set, and 0.9818\/0.9836 on F-data set, with consistent performance across varying negative sampling ratios and entity-wise split settings. Under a leakage-controlled protocol in which GIP kernels were recomputed exclusively from the training DDAs within each fold, MVGCL retained the highest AUC and AUPR among the compared GIP-based models, with AUC values of 0.9029, 0.9422, and 0.9145 on B-data set, C-data set, and F-data set, respectively. Case analyses on Alzheimer\u2019s disease and Parkinson\u2019s disease further show that MVGCL ranks literature-supported drugs highly and prioritizes biologically plausible candidates for follow-up investigation, supporting its utility for evidence-aware drug repositioning.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01242","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:01:43Z","timestamp":1786107703000},"page":"10339-10355","source":"Crossref","is-referenced-by-count":0,"title":["MVGCL: Noise-Robust\nMulti-Source Similarity Fusion\nand Type-Aware Dual-Pathway Learning for Drug Repositioning"],"prefix":"10.1021","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8979-4386","authenticated-orcid":true,"given":"Anhong","family":"Yu","sequence":"first","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiao","family":"Ke","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Shu","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangdong Pharmaceutical University , , ,","place":["Guangzhou, Guangdong, China, 510062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longgang Second People\u2019s Hospital , , ,","place":["Shenzhen, Guangdong, China, 518112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-8674","authenticated-orcid":true,"given":"Yongxia","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]},{"name":"The First Affiliated Hospital of Guangdong Pharmaceutical University , , ,","place":["Guangzhou, Guangdong, China, 510062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luonan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , , ,","place":["Guangzhou, Guangdong, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026083104314821000_cit1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jhealeco.2016.01.012","article-title":"Innovation in the pharmaceutical\nindustry: New estimates of R&D costs","volume":"47","author":"DiMasi","year":"2016","journal-title":"J.\nHealth Econ."},{"issue":"8","key":"2026083104314821000_cit2","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","article-title":"Drug repositioning:\nIdentifying and developing new\nuses for existing drugs","volume":"3","author":"Ashburn","year":"2004","journal-title":"Nat. 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