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The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.<\/jats:p>","DOI":"10.1093\/nargab\/lqad061","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T05:25:27Z","timestamp":1686201927000},"source":"Crossref","is-referenced-by-count":17,"title":["Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation"],"prefix":"10.1093","volume":"5","author":[{"given":"Rafael R C","family":"Cuadrat","sequence":"first","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6151-5097","authenticated-orcid":false,"given":"Adelheid","family":"Kratzer","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5763-9388","authenticated-orcid":false,"given":"Hector Giral","family":"Arnal","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-1040","authenticated-orcid":false,"given":"Anja\u00a0C","family":"Rathgeber","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"},{"name":"Berlin Institute of Health (BIH) , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-4802","authenticated-orcid":false,"given":"Katarzyna","family":"Wreczycka","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3045-8234","authenticated-orcid":false,"given":"Alexander","family":"Blume","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2641-0916","authenticated-orcid":false,"given":"Irem B","family":"G\u00fcnd\u00fcz","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Ebenal","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Mauno","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Osberg","sequence":"additional","affiliation":[{"name":"Bioinformatics & Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max-Delbr\u00fcck-Center for Molecular Medicine Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoo","family":"Moobed","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hartung","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jakobs","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-6809","authenticated-orcid":false,"given":"Claudio","family":"Seppelt","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"},{"name":"Universit\u00e4tsklinikum Frankfurt am Main , Medizinische Klinik 3, Klinik f\u00fcr Kardiologie und Angiologie , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-924X","authenticated-orcid":false,"given":"Denitsa","family":"Meteva","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Cardiology , Campus Benjamin Franklin , Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) , partner site Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-8808","authenticated-orcid":false,"given":"Arash","family":"Haghikia","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - 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