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However, current methods largely rely on global neighborhood aggregation, which treats node contexts as homogeneous and overlooks fine-grained structural and semantic heterogeneity. Moreover, they often model ncRNAs and drugs as interchangeable nodes, disregarding their biological distinctions and asymmetric interactions, and failing to effectively integrate modality-specific and cross-modal features. To overcome these limitations, we propose HDBI, a higher-order dynamic disentangled framework for predicting ncRNA-drug resistance associations. HDBI integrates multiview hypergraph learning, disentangled representation modeling, and bidirectional cross-modal updating to capture heterogeneous topological and semantic patterns within ncRNA and drug spaces while preserving modality-specific characteristics and enabling cross-modal information exchange. Extensive experiments on two benchmark data sets demonstrate that HDBI consistently outperforms state-of-the-art methods. Case studies on 5-FU and Docetaxel further support the biological relevance of the predictions, with 22\/30 and 21\/30 top-ranked ncRNAs supported by PubMed evidence, respectively. Functional enrichment and molecular docking analyses further linked these predictions to drug-relevant pathways and structurally plausible regulatory interactions. These findings suggest that HDBI provides an effective and interpretable framework for prioritizing ncRNA-mediated drug resistance associations and guiding downstream mechanistic investigation.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01116","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:26:04Z","timestamp":1783671964000},"page":"8633-8650","source":"Crossref","is-referenced-by-count":0,"title":["Higher-Order Dynamic\nDisentangled Intent Sensing and\nBidirectional Joint Updating Framework for NcRNA-Drug Resistance Association\nPrediction"],"prefix":"10.1021","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9140-3653","authenticated-orcid":true,"given":"Tiyao","family":"Liu","sequence":"first","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shudong","family":"Wang","sequence":"additional","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoming","family":"Feng","sequence":"additional","affiliation":[{"name":"Macao Polytechnic University , , ,","place":["Macao, China, 999708"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7539-5970","authenticated-orcid":true,"given":"Shaoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Qingdao University of Technology , , ,","place":["Qingdao, China, 266525"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Gao","sequence":"additional","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengtao","family":"Ding","sequence":"additional","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanchen","family":"Pang","sequence":"additional","affiliation":[{"name":"China University of Petroleum (East China) , , ,","place":["Qingdao, China, 266580"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"issue":"23","key":"2026072709090682400_cit1","doi-asserted-by":"publisher","first-page":"6451","DOI":"10.1016\/j.cell.2024.10.024","article-title":"Small and long non-coding rnas: Past, present, and\nfuture","volume":"187","author":"Chen","year":"2024","journal-title":"Cell"},{"issue":"1","key":"2026072709090682400_cit2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-020-00636-z","article-title":"Functional roles\nand networks of non-coding rnas in\nthe pathogenesis of neurodegenerative diseases","volume":"27","author":"Wu","year":"2020","journal-title":"J. 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