{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:08:30Z","timestamp":1789103310061,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["252102210070"],"award-info":[{"award-number":["252102210070"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["252102311174"],"award-info":[{"award-number":["252102311174"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nanyang Basic and Frontier Research Project","award":["23JCQY2020"],"award-info":[{"award-number":["23JCQY2020"]}]},{"name":"Nanyang Science and Technology Research Project","award":["23KJGG008"],"award-info":[{"award-number":["23KJGG008"]}]},{"name":"Nanyang Science and Technology Research Project","award":["24KJGG045"],"award-info":[{"award-number":["24KJGG045"]}]},{"name":"Interdisciplinary Sciences Project"},{"DOI":"10.13039\/501100017278","name":"Nanyang Institute of Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100017278","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Tumor heterogeneity arises from complex interactions among diverse biological factors, posing a major challenge for the development of robust multi-omics data integration methods. While the existing Tumor Multi-Omics pre-trained Network (TMO-Net) enables the fusion of multi-omics features into unified representations, its practical utility is constrained by issues such as missing modalities, incomplete within-omics data, and high-dimensional noise. To overcome these limitations, we propose TMO-Net+, an enhanced architecture specifically designed to improve the robustness and reliability of multi-omics modeling. Methods: TMO-Net+ introduces several coordinated architectural enhancements. First, a feature attention encoder is applied to each omics data type to reduce the influence of modality-dependent input variation. Second, we combine a gated Mixture-of-Experts (MoE) module with a Product-of Experts (PoE) mechanism to capture sample-specific contributions and enable robust inference even when partial omics data are available. Additionally, a supervised deep classification head with a tailored loss function is incorporated to enhance the separability of learned embeddings in the latent space. Results: Extensive experiments on pan-cancer datasets demonstrate that TMO-Net+ consistently outperforms the original TMO-Net, as measured by LogME scores. Furthermore, in various downstream tasks (e.g., pan-cancer classification, primary\/metastatic site prediction, and prognostic modeling), TMO-Net+ achieves superior performance under partial-omics settings, which proves that it enhances the robustness and cross-cancer transferability of the multi-omics representations. Conclusions: The proposed TMO-Net+ improves the robustness and cross-cancer transferability of multi-omics representations within the evaluated TCGA cohorts. Biological interpretability analyses further show that TMO-Net+ prioritizes established cancer-driver genes, preserves cancer-dependent molecular-state information, and adaptively redistributes relative modality contributions across molecular states. By addressing modality-level missingness and modality-dependent input variation, it offers a reliable framework for integrative tumor analysis within the evaluated TCGA cohorts.<\/jats:p>","DOI":"10.3390\/genes17091085","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:02:48Z","timestamp":1788962568000},"page":"1085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TMO-Net+: An Enhanced Tumor Multi-Omics Pre-Trained Network for Multi-Task Learning in Oncology"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0038-6519","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7980-9816","authenticated-orcid":false,"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Shuyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kaiyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xiangzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4647-7202","authenticated-orcid":false,"given":"Lilu","family":"Guo","sequence":"additional","affiliation":[{"name":"Academy for Electronic Information Discipline Studies, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanyang Central Hospital, Gongnong Road 312, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Qingzhi","family":"Su","sequence":"additional","affiliation":[{"name":"Xinye County Xinruo Electronic Technology Co., Ltd., No. 009 Xingye Road, Xinye County, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","article-title":"Clonal heterogeneity and tumor evolution: Past, present, and the future","volume":"168","author":"McGranahan","year":"2017","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41568-020-0290-x","article-title":"A compendium of mutational cancer driver genes","volume":"20","author":"Mularoni","year":"2020","journal-title":"Nat. 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