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Accurate time-to-event CHD prediction models with high-dimensional DNA methylation and clinical features may assist with early prediction and intervention strategies. We developed a state-of-the-art deep learning autoencoder survival analysis model (AESurv) to effectively analyze high-dimensional blood DNA methylation features and traditional clinical risk factors by learning low-dimensional representation of participants for time-to-event CHD prediction. We demonstrated the utility of our model in two cohort studies: the Strong Heart Study cohort (SHS), a prospective cohort studying cardiovascular disease and its risk factors among American Indians adults; the Women\u2019s Health Initiative (WHI), a prospective cohort study including randomized clinical trials and observational study to improve postmenopausal women\u2019s health with one of the main focuses on cardiovascular disease. Our AESurv model effectively learned participant representations in low-dimensional latent space and achieved better model performance (concordance index-C index of 0.864\u2009\u00b1\u20090.009 and time-to-event mean area under the receiver operating characteristic curve-AUROC of 0.905\u2009\u00b1\u20090.009) than other survival analysis models (Cox proportional hazard, Cox proportional hazard deep neural network survival analysis, random survival forest, and gradient boosting survival analysis models) in the SHS. We further validated the AESurv model in WHI and also achieved the best model performance. The AESurv model can be used for accurate CHD prediction and assist health care professionals and patients to perform early intervention strategies. We suggest using AESurv model for future time-to-event CHD prediction based on DNA methylation features.<\/jats:p>","DOI":"10.1093\/bib\/bbae479","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:36:16Z","timestamp":1727325376000},"source":"Crossref","is-referenced-by-count":3,"title":["AESurv: autoencoder survival analysis for accurate early prediction of coronary heart disease"],"prefix":"10.1093","volume":"25","author":[{"given":"Yike","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Earth and Environmental Sciences, University of Texas at Arlington , 500 Yates Street, Arlington, TX, 76019 ,","place":["USA"]},{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"given":"Arce","family":"Domingo-Relloso","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases Epidemiology , National Center for Epidemiology, , C. de Melchor Fern\u00e1ndez Almagro, 5, Fuencarral-El Pardo, 5, Madrid, 28029 ,","place":["Spain"]},{"name":"Carlos III Health Institute , National Center for Epidemiology, , C. de Melchor Fern\u00e1ndez Almagro, 5, Fuencarral-El Pardo, 5, Madrid, 28029 ,","place":["Spain"]},{"name":"Department of Statistics and Operations Research, University of Valencia , Carrer del Dr. Moliner, 50, Valencia, 46100 ,","place":["Spain"]},{"name":"Department of Biostatistics, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"given":"Allison","family":"Kupsco","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"given":"Marianthi-Anna","family":"Kioumourtzoglou","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"given":"Maria","family":"Tellez-Plaza","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases Epidemiology , National Center for Epidemiology, , C. de Melchor Fern\u00e1ndez Almagro, 5, Fuencarral-El Pardo, 5, Madrid, 28029 ,","place":["Spain"]},{"name":"Carlos III Health Institute , National Center for Epidemiology, , C. de Melchor Fern\u00e1ndez Almagro, 5, Fuencarral-El Pardo, 5, Madrid, 28029 ,","place":["Spain"]}]},{"given":"Jason G","family":"Umans","sequence":"additional","affiliation":[{"name":"Department of Medicine, Georgetown-Howard Universities Center for Clinical and Translational Science , 4000 Reservoir Road NW, Washington, DC, 20007 ,","place":["USA"]}]},{"given":"Amanda M","family":"Fretts","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington , 3980 15th Ave NE, Seattle, WA, 98195 ,","place":["USA"]}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for American Indian Health Research , Department of Biostatistics and Epidemiology, , 801 N.E. 13th Street, Oklahoma City, OK, 73104 ,","place":["USA"]},{"name":"The University of Oklahoma Health Sciences Center , Department of Biostatistics and Epidemiology, , 801 N.E. 13th Street, Oklahoma City, OK, 73104 ,","place":["USA"]}]},{"given":"Peter F","family":"Schnatz","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and Internal Medicine, Reading Hospital\/Tower Health & Drexel University , 301 S 7th Ave, West Reading, PA, 19611 ,","place":["USA"]}]},{"given":"Ramon","family":"Casanova","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , 475 Vine St, Winston Salem, NC, 27101 ,","place":["USA"]}]},{"given":"Lisa Warsinger","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Medicine , Division of Cardiology, , 2300 Eye Street, NW, Washington, DC, 20037 ,","place":["USA"]},{"name":"George Washington University , Division of Cardiology, , 2300 Eye Street, NW, Washington, DC, 20037 ,","place":["USA"]}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Human Genetics , David Geffen School of Medicine, , 695 Charles E. Young Drive South, Los Angeles, CA, 90095 ,","place":["USA"]},{"name":"University of California, Los Angeles (UCLA) , David Geffen School of Medicine, , 695 Charles E. Young Drive South, Los Angeles, CA, 90095 ,","place":["USA"]},{"name":"Altos Lab Inc , Granta Park, Little Abington, Cambridge, CB21 6GQ ,","place":["United Kingdom"]}]},{"given":"JoAnn E","family":"Manson","sequence":"additional","affiliation":[{"name":"Department of Medicine , Brigham and Women\u2019s Hospital, , 900 Commonwealth Ave, Boston, MA, 02215 ,","place":["USA"]},{"name":"Harvard Medical School , Brigham and Women\u2019s Hospital, , 900 Commonwealth Ave, Boston, MA, 02215 ,","place":["USA"]}]},{"given":"Shelley A","family":"Cole","sequence":"additional","affiliation":[{"name":"Population Health Program, Texas Biomedical Research Institute , 8715 W. Military Dr., San Antonio, TX, 78227 ,","place":["USA"]}]},{"given":"Haotian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"given":"Eric A","family":"Whitsel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , Gillings School of Global Public Health and Department of Medicine, School of Medicine, , 135 Dauer Drive, Chapel Hill, NC, 27599 ,","place":["USA"]},{"name":"University of North Carolina at Chapel Hill , Gillings School of Global Public Health and Department of Medicine, School of Medicine, , 135 Dauer Drive, Chapel Hill, NC, 27599 ,","place":["USA"]}]},{"given":"Andrea A","family":"Baccarelli","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]},{"name":"Harvard T.H. Chan School of Public Health, Harvard University , 677 Huntington Avenue, Boston, MA, 02115 ,","place":["USA"]}]},{"given":"Ana","family":"Navas-Acien","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , 722 West 168th Street, New York, NY, 10032 ,","place":["USA"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-2101","authenticated-orcid":false,"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles (UCLA) , 650 Charles E. Young Drive South, Los Angeles, CA, 90095 ,","place":["USA"]},{"name":"Department of Molecular and Medical Pharmacology , David Geffen School of Medicine, , Los Angeles (UCLA), 650 Charles E. 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