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Constructing multi-omics networks with respect to the trait(s) of interest provides an opportunity to understand relationships between molecular features but integration is challenging due to multiple data sets with high dimensionality. One approach is to use canonical correlation to integrate one or two omics types and a single trait of interest. However, these types of methods may be limited due to (1) not accounting for higher-order correlations existing among features, (2) computational inefficiency when extending to more than two omics data when using a penalty term-based sparsity method, and (3) lack of flexibility for focusing on specific correlations (e.g., omics-to-phenotype correlation versus omics-to-omics correlations). In this work, we have developed a novel multi-omics network analysis pipeline called Sparse Generalized Tensor Canonical Correlation Analysis Network Inference (SGTCCA-Net) that can effectively overcome these limitations. We also introduce an implementation to improve the summarization of networks for downstream analyses. Simulation and real-data experiments demonstrate the effectiveness of our novel method for inferring omics networks and features of interest.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011842","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T16:05:09Z","timestamp":1744646709000},"page":"e1011842","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["A generalized higher-order correlation analysis framework for multi-omics network inference"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0222-1784","authenticated-orcid":true,"given":"Weixuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Pratte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Castaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Hersh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Bowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnoush","family":"Banaei-Kashani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-5459","authenticated-orcid":true,"given":"Katerina J.","family":"Kechris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"pcbi.1011842.ref001","article-title":"A survey on multi-view learning","author":"C Xu","year":"2013","journal-title":"arXiv preprint"},{"key":"pcbi.1011842.ref002","first-page":"184","volume-title":"ICDM","author":"S Bickel","year":"2004"},{"key":"pcbi.1011842.ref003","doi-asserted-by":"crossref","unstructured":"Kalayeh M, Idrees H, Shah M. 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