{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T23:15:18Z","timestamp":1774912518623,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: In the era of network medicine and the rapid growth of paired time series mRNA\/microRNA expression experiments, there is an urgent need for pathway enrichment analysis methods able to capture the time- and condition-specific \u2018active parts\u2019 of the biological circuitry as well as the microRNA impact. Current methods ignore the multiple dynamical \u2018themes\u2019\u2014in the form of enriched biologically relevant microRNA-mediated subpathways\u2014that determine the functionality of signaling networks across time.<\/jats:p>\n               <jats:p>Results: To address these challenges, we developed time-vaRying enriCHment integrOmics Subpathway aNalysis tOol (CHRONOS) by integrating time series mRNA\/microRNA expression data with KEGG pathway maps and microRNA-target interactions. Specifically, microRNA-mediated subpathway topologies are extracted and evaluated based on the temporal transition and the fold change activity of the linked genes\/microRNAs. Further, we provide measures that capture the structural and functional features of subpathways in relation to the complete organism pathway atlas. Our application to synthetic and real data shows that CHRONOS outperforms current subpathway-based methods into unraveling the inherent dynamic properties of pathways.<\/jats:p>\n               <jats:p>Availability and implementation: CHRONOS is freely available at http:\/\/biosignal.med.upatras.gr\/chronos\/.<\/jats:p>\n               <jats:p>Contact: \u00a0tassos.bezerianos@nus.edu.sg.<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv673","type":"journal-article","created":{"date-parts":[[2015,11,15]],"date-time":"2015-11-15T01:38:21Z","timestamp":1447551501000},"page":"884-892","source":"Crossref","is-referenced-by-count":34,"title":["<i>CHRONOS<\/i>: a time-varying method for microRNA-mediated subpathway enrichment analysis"],"prefix":"10.1093","volume":"32","author":[{"given":"Aristidis G.","family":"Vrahatis","sequence":"first","affiliation":[{"name":"1 Department of Computer Engineering and Informatics,"},{"name":"2 Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina","family":"Dimitrakopoulou","sequence":"additional","affiliation":[{"name":"3 Centre for Cancer Biomarkers CCBIO and Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panos","family":"Balomenos","sequence":"additional","affiliation":[{"name":"1 Department of Computer Engineering and Informatics,"},{"name":"2 Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios K.","family":"Tsakalidis","sequence":"additional","affiliation":[{"name":"1 Department of Computer Engineering and Informatics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios","family":"Bezerianos","sequence":"additional","affiliation":[{"name":"2 Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece,"},{"name":"4 SINAPSE Institute, Center of Life Sciences, National University of Singapore, Singapore 117456"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,11,14]]},"reference":[{"key":"2023020111551416500_btv673-B1","doi-asserted-by":"crossref","first-page":"e29979","DOI":"10.1371\/journal.pone.0029979","article-title":"Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression","volume":"7","author":"Allantaz","year":"2012","journal-title":"PloS One"},{"key":"2023020111551416500_btv673-B2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: a network-based approach to human disease","volume":"12","author":"Barab\u00e1si","year":"2011","journal-title":"Nat. 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