{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T03:22:26Z","timestamp":1768274546190,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RESEARCH \u2013 CREATE \u2013 INNOVATE","award":["T1EDK-00940"],"award-info":[{"award-number":["T1EDK-00940"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tissue-specific gene methylation events are key to the pathogenesis of several diseases and can be utilized for diagnosis and monitoring. Here, we established an in silico pipeline to analyze high-throughput methylome datasets to identify specific methylation fingerprints in three pathological entities of major burden, i.e., breast cancer (BrCa), osteoarthritis (OA) and diabetes mellitus (DM). Differential methylation analysis was conducted to compare tissues\/cells related to the pathology and different types of healthy tissues, revealing Differentially Methylated Genes (DMGs). Highly performing and low feature number biosignatures were built with automated machine learning, including: (1) a five-gene biosignature discriminating BrCa tissue from healthy tissues (AUC 0.987 and precision 0.987), (2) three equivalent OA cartilage-specific biosignatures containing four genes each (AUC 0.978 and precision 0.986) and (3) a four-gene pancreatic \u03b2-cell-specific biosignature (AUC 0.984 and precision 0.995). Next, the BrCa biosignature was validated using an independent ccfDNA dataset showing an AUC and precision of 1.000, verifying the biosignature\u2019s applicability in liquid biopsy. Functional and protein interaction prediction analysis revealed that most DMGs identified are involved in pathways known to be related to the studied diseases or pointed to new ones. Overall, our data-driven approach contributes to the maximum exploitation of high-throughput methylome readings, helping to establish specific disease profiles to be applied in clinical practice and to understand human pathology.<\/jats:p>","DOI":"10.3390\/ijms23062959","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:30:38Z","timestamp":1646825438000},"page":"2959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach"],"prefix":"10.3390","volume":"23","author":[{"given":"Makrina","family":"Karaglani","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Panagopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismini","family":"Baltsavia","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Medicine, University of Crete, GR-71003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevi","family":"Apalaki","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodosis","family":"Theodosiou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Iliopoulos","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Medicine, University of Crete, GR-71003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Tsamardinos","sequence":"additional","affiliation":[{"name":"JADBio Gnosis DA S.A., Science and Technology Park of Crete, GR-70013 Heraklion, Greece"},{"name":"Department of Computer Science, University of Crete, GR-70013 Heraklion, Greece"},{"name":"Institute of Applied and Computational Mathematics, Foundation for Research and Technology\u2014Hellas, GR-70013 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5832-4257","authenticated-orcid":false,"given":"Ekaterini","family":"Chatzaki","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece"},{"name":"Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, GR-71410 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrg1655","article-title":"DNA methylation and human disease","volume":"6","author":"Robertson","year":"2005","journal-title":"Nat. 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