{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:45:09Z","timestamp":1787168709052,"version":"build-2736575974"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Computational analyses of bulk and single-cell omics provide translational insights into complex diseases, such as COVID-19, by revealing molecules, cellular phenotypes, and signalling patterns that contribute to unfavourable clinical outcomes. Current in silico approaches dovetail differential abundance, biostatistics, and machine learning, but often overlook non-linear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically-informed sparse deep learning model, to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests SJARACNe co-regulation and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and Implementation<\/jats:title>\n                    <jats:p>APNet\u2019s R, Python scripts and Cytoscape methodologies are available at https:\/\/github.com\/BiodataAnalysisGroup\/APNet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary Information<\/jats:title>\n                    <jats:p>Supplementary information can be accessed in Zenodo (10.5281\/zenodo.14680520).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf063","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T15:19:00Z","timestamp":1738768740000},"source":"Crossref","is-referenced-by-count":8,"title":["APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19"],"prefix":"10.1093","author":[{"given":"George I","family":"Gavriilidis","sequence":"first","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Vasileiou","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas , Thessaloniki,","place":["Greece"]},{"name":"Democritus University of Thrace Department of Molecular Biology and Genetics, , Alexandroupolis,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Dimitsaki","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Karakatsoulis","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Giannakakis","sequence":"additional","affiliation":[{"name":"Democritus University of Thrace Department of Molecular Biology and Genetics, , Alexandroupolis,","place":["Greece"]},{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, , Athens, 11527,","place":["Greece"]},{"name":"National and Kapodistrian University of Athens Research Institute of Maternal and Child Health and Precision Medicine, , Athens, 11527,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios A","family":"Pavlopoulos","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Biomedical Research, BSRC \u201cAlexander Fleming\u201d , Vari,","place":["Greece"]},{"name":"National and Kapodistrian University of Athens Center of New Biotechnologies & Precision Medicine, Department of Medicine, School of Health Sciences, , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotis","family":"Psomopoulos","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,8]]},"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf063\/61813126\/btaf063.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf063\/61813126\/btaf063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T13:56:21Z","timestamp":1739022981000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article\/doi\/10.1093\/bioinformatics\/btaf063\/8005858"}},"subtitle":[],"editor":[{"given":"Pier","family":"Luigi Martelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf063","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.11.575161","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,8]]},"article-number":"btaf063"}}