{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:04:14Z","timestamp":1785171854327,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Multi-omics datasets are increasingly used for disease classification, but differences in scale, distribution, and resolution across omics layers complicate their integration. Conventional fusion approaches may overlook nonlinear cross-omics dependencies and structured sample\u2013feature relationships. Here, we propose FastMI-HGNet, a two-stream heterogeneous graph neural network for multi-omics disease classification. Methods: The framework uses fast mutual information (FastMI) to construct dependency edge priors for a heterogeneous graph that connects sample and feature nodes. A Transformer-based data stream captures vector-level feature interactions, while a graph attention stream models structural dependencies among samples and molecular features. An uncertainty-aware ensemble further improves stability under small-sample and noisy multi-omics settings. Results: Evaluated on five public multi-omics benchmarks\u2014ROSMAP, LGG, BRCA, and the more challenging COAD tumor-stage classification task, together with KIPAN as a ceiling-level proof-of-concept benchmark\u2014FastMI-HGNet achieved competitive classification performance while supporting interpretable biomarker prioritization. In BRCA, SHAP-based analysis highlighted model-prioritized genes such as FOXC1 and SOX10. Conclusions: FastMI-HGNet supports interpretable multi-omics disease classification and biomarker prioritization.<\/jats:p>","DOI":"10.3390\/genes17080865","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FastMI-HGNet: A Two-Stream Heterogeneous Graph Neural Network for Multi-Omics Disease Classification"],"prefix":"10.3390","volume":"17","author":[{"given":"Xufeng","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bipeng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuji","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-7808","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e315","DOI":"10.1002\/mco2.315","article-title":"Applications of Multi-omics Analysis in Human Diseases","volume":"4","author":"Chen","year":"2023","journal-title":"MedComm"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, S., Chaudhary, K., and Garmire, L.X. 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