{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:22:33Z","timestamp":1767180153092,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013660","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017266","name":"Gobierno de Navarra","doi-asserted-by":"publisher","award":["0011-3947-2021-000023"],"award-info":[{"award-number":["0011-3947-2021-000023"]}],"id":[{"id":"10.13039\/501100017266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017266","name":"Gobierno de Navarra","doi-asserted-by":"publisher","award":["0011-2750-2022-000000"],"award-info":[{"award-number":["0011-2750-2022-000000"]}],"id":[{"id":"10.13039\/501100017266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Micro-RNAs (miRNA) and their relationship with messenger RNAs (mRNA) have been widely associated with disease development and progression. Post-transcriptional coregulatory networks are sets of miRNA-mRNA interactions that regulate specific genetic behaviors through their combined activity. However, identifying reliable sets of such interactions associated with specific diseases remains challenging, partly due to the high rate of false positives and the lack of user-friendly tools developed for this purpose. In this work, we introduce a new Python package called RNACOREX (RNA CORegulatory network EXplorer and classifier). RNACOREX is a new, easy-to-use tool that allows researchers to find disease associated post-transcriptional coregulatory networks and use them to classify new unseen observations of miRNA and mRNA quantifications. RNACOREX combines structural information from curated databases with expression data analysis, using conditional mutual information to infer reliable sets of miRNA\u2013mRNA interactions. These sets are then used to build probabilistic models based on Conditional Linear Gaussian (CLG) classifiers, which allow both prediction on new samples and validation of the inferred networks.<\/jats:p>\n                  <jats:p>To demonstrate its capabilities, we tested RNACOREX in 13 different databases from the The Cancer Genome Atlas Program, generating the associated post-transcriptional coregulatory networks and extracting classification performance metrics for each tumor type. Specifically, we used RNACOREX to classify patients according to their survival time in each cancer type, highlighting miRNA\u2013mRNA interactions that consistently appeared across different cancer types. The results show that RNACOREX achieves competitive predictive performance compared to widely used classification algorithms, while offering the added benefit of interpretability through its graph-based modeling framework.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013660","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:41:02Z","timestamp":1762195262000},"page":"e1013660","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["RNACOREX - RNA coregulatory network explorer and classifier"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-6635","authenticated-orcid":true,"given":"Aitor","family":"Oviedo-Madrid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-0453","authenticated-orcid":true,"given":"Jos\u00e9","family":"Gonz\u00e1lez-Gomariz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Arma\u00f1anzas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"7006","key":"pcbi.1013660.ref001","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature02871","article-title":"The functions of animal microRNAs","volume":"431","author":"V Ambros","year":"2004","journal-title":"Nature."},{"issue":"5","key":"pcbi.1013660.ref002","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.gpb.2012.10.001","article-title":"One decade of development and evolution of microRNA target prediction algorithms","volume":"10","author":"PH Reyes-Herrera","year":"2012","journal-title":"Genomics Proteomics Bioinformatics."},{"issue":"2","key":"pcbi.1013660.ref003","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/biom.12266","article-title":"miRNA-target gene regulatory networks: a Bayesian integrative approach to biomarker selection with application to kidney cancer","volume":"71","author":"T Chekouo","year":"2015","journal-title":"Biometrics."},{"issue":"5","key":"pcbi.1013660.ref004","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41593-019-0382-7","article-title":"A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data","volume":"22","author":"Q Wang","year":"2019","journal-title":"Nat Neurosci."},{"key":"pcbi.1013660.ref005","doi-asserted-by":"crossref","unstructured":"Ben-Gal I. 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