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Accurate ncRNA\u2013disease association prediction is essential for understanding disease mechanisms and developing treatments. Existing methods often focus on single tasks like lncRNA\u2013disease associations (LDAs), miRNA\u2013disease associations (MDAs), or lncRNA\u2013miRNA interactions (LMIs), and fail to exploit heterogeneous graph characteristics. We propose ACLNDA, an asymmetric graph contrastive learning framework for analyzing heterophilic ncRNA\u2013disease associations. It constructs inter-layer adjacency matrices from the original lncRNA, miRNA, and disease associations, and uses a Top-K intra-layer similarity edges construction approach to form a triple-layer heterogeneous graph. Unlike traditional works, to account for both node attribute features (ncRNA\/disease) and node preference features (association), ACLNDA employs an asymmetric yet simple graph contrastive learning framework to maximize one-hop neighborhood context and two-hop similarity, extracting ncRNA\u2013disease features without relying on graph augmentations or homophily assumptions, reducing computational cost while preserving data integrity. Our framework is capable of being applied to a universal range of potential LDA, MDA, and LMI association predictions. Further experimental results demonstrate superior performance to other existing state-of-the-art baseline methods, which shows its potential for providing insights into disease diagnosis and therapeutic target identification. The source code and data of ACLNDA is publicly available at https:\/\/github.com\/AI4Bread\/ACLNDA.<\/jats:p>","DOI":"10.1093\/bib\/bbae533","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T14:10:41Z","timestamp":1729692641000},"source":"Crossref","is-referenced-by-count":5,"title":["ACLNDA: an asymmetric graph contrastive learning framework for predicting noncoding RNA\u2013disease associations in heterogeneous graphs"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9086-3982","authenticated-orcid":false,"given":"Laiyi","family":"Fu","sequence":"first","affiliation":[{"name":"School of Automation Science and Engineering, Xi\u2019an Jiaotong University , Xi\u2019an, Shannxi 710049 ,","place":["China"]},{"name":"Research Institute, Xi\u2019an Jiaotong University , Zhejiang, Hangzhou, Zhejiang 311200 ,","place":["China"]},{"name":"Sichuan Digital Economy Industry Development Research Institute , Chengdu, Sichuan 610036 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiYuan","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Xi\u2019an Jiaotong University , Xi\u2019an, Shannxi 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Xi\u2019an Jiaotong University , Xi\u2019an, Shannxi 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinke","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Xi\u2019an Jiaotong University , Xi\u2019an, Shannxi 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-4762","authenticated-orcid":false,"given":"Hongqiang","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Xi\u2019an Jiaotong University , Xi\u2019an, Shannxi 710049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"2024102314102624100_ref1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrc.2017.99","article-title":"Non-coding rna networks in cancer","volume":"18","author":"Anastasiadou","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"2024102314102624100_ref2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/gastro\/goaa060","article-title":"lncRNA-PACER upregulatesCOX-2and PGE2 through the NF-\u03baB pathway to promote the proliferation and invasion of 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