{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T04:47:12Z","timestamp":1780116432453,"version":"3.54.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    The host epigenetic landscape rapidly changes during SARS-CoV-2 infection, and evidence suggest that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation changes in immune cells and alterations to epigenetic clocks in blood relate to severe COVID-19. However, a longitudinal assessment of DNA methylation states and epigenetic clocks in blood from healthy individuals prior to and following test-confirmed non-hospitalized COVID-19 has not been performed. Moreover, the impact of mRNA COVID-19 vaccines upon the host epigenome remains understudied. Here, we first examined DNA methylation states in the blood of 21 participants prior to and following test-confirmed COVID-19 diagnosis at a median time frame of 8.35\u00a0weeks; 756 CpGs were identified as differentially methylated following COVID-19 diagnosis in blood at an FDR adjusted\n                    <jats:italic>p<\/jats:italic>\n                    -value &amp;lt; 0.05. These CpGs were enriched in the gene body, and the northern and southern shelf regions of genes involved in metabolic pathways. Integrative analysis revealed overlap among genes identified in transcriptional SARS-CoV-2 infection datasets. Principal component-based epigenetic clock estimates of PhenoAge and GrimAge significantly increased in people over 50 following infection by an average of 2.1 and 0.84\u00a0years. In contrast, PCPhenoAge significantly decreased in people fewer than 50 following infection by an average of 2.06\u00a0years. This observed divergence in epigenetic clocks following COVID-19 was related to age and immune cell-type compositional changes in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, B cells, granulocytes, plasmablasts, exhausted T cells, and na\u00efve T cells. Complementary longitudinal epigenetic clock analyses of 36 participants prior to and following Pfizer and Moderna mRNA-based COVID-19 vaccination revealed that vaccination significantly reduced principal component-based Horvath epigenetic clock estimates in people over 50 by an average of 3.91\u00a0years for those who received Moderna. This reduction in epigenetic clock estimates was significantly related to chronological age and immune cell-type compositional changes in B cells and plasmablasts pre- and post-vaccination. These findings suggest the potential utility of epigenetic clocks as a biomarker of COVID-19 vaccine responses. Future research will need to unravel the significance and durability of short-term changes in epigenetic age related to COVID-19 exposure and mRNA vaccination.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.819749","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T02:35:03Z","timestamp":1654223703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination"],"prefix":"10.3389","volume":"13","author":[{"given":"Alina P. S.","family":"Pang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert T.","family":"Higgins-Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Comite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Raica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Arboleda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Went","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tavis","family":"Mendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schotsaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Dwaraka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishomwa C.","family":"Ndhlovu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Corley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.10.10.21264827","article-title":"Heterologous SARS-CoV-2 Booster Vaccinations - Preliminary Report","author":"Atmar","year":"2021","journal-title":"medRxiv"},{"key":"B2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/nejmoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13148-021-01102-9","article-title":"Blood DNA Methylation and COVID-19 Outcomes","volume":"13","author":"Balnis","year":"2021","journal-title":"Clin. Epigenet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e73420","DOI":"10.1101\/2021.08.30.21262858","article-title":"DunedinPACE: A DNA Methylation Biomarker of the Pace of Aging","volume":"11","author":"Belsky","year":"2021","journal-title":"bioRxiv"},{"key":"B5","doi-asserted-by":"publisher","first-page":"E4104","DOI":"10.1073\/pnas.1506264112","article-title":"Quantification of Biological Aging in Young Adults","volume":"112","author":"Belsky","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54870","article-title":"Quantification of the Pace of Biological Aging in Humans through a Blood Test, the DunedinPoAm DNA Methylation Algorithm","volume":"9","author":"Belsky","year":"2020","journal-title":"Elife"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.immuni.2020.11.017","article-title":"Longitudinal Multi-Omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19","volume":"53","author":"Bernardes","year":"2020","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","first-page":"11877","DOI":"10.1074\/jbc.m010512200","article-title":"CARD11 and CARD14 Are Novel Caspase Recruitment Domain (CARD)\/Membrane-associated Guanylate Kinase (MAGUK) Family Members that Interact with BCL10 and Activate NF-\u039ab*","volume":"276","author":"Bertin","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0140-6736(21)01420-3","article-title":"Immunogenicity and Reactogenicity of BNT162b2 Booster in ChAdOx1-S-Primed Participants (CombiVacS): a Multicentre, Open-Label, Randomised, Controlled, Phase 2 Trial","volume":"398","author":"Borobia","year":"2021","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/1471-2105-15-312","article-title":"Evaluation of Microarray-Based DNA Methylation Measurement Using Technical Replicates: the Atherosclerosis Risk in Communities (ARIC) Study","volume":"15","author":"Bose","year":"2014","journal-title":"BMC Bioinforma."},{"key":"B12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.molcel.2016.04.008","article-title":"An Epigenetic Clock Measures Accelerated Aging in Treated HIV Infection","volume":"62","author":"Boulias","year":"2016","journal-title":"Mol. Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4767","DOI":"10.1093\/bioinformatics\/btz456","article-title":"eFORGE v2.0: Updated Analysis of Cell Type-specific Signal in Epigenomic Data","volume":"35","author":"Breeze","year":"2019","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"103339","DOI":"10.1016\/j.ebiom.2021.103339","article-title":"Epigenome-wide Association Study of COVID-19 Severity with Respiratory Failure","volume":"66","author":"Castro de Moura","year":"2021","journal-title":"EBioMedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1038\/s41591-018-0237-x","article-title":"Longitudinal Personal DNA Methylome Dynamics in a Human with a Chronic Condition","volume":"24","author":"Chen","year":"2018","journal-title":"Nat. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41586-021-03739-1","article-title":"Age-related Immune Response Heterogeneity to SARS-CoV-2 Vaccine BNT162b2","volume":"596","author":"Collier","year":"2021","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/JLB.5HI0720-466R","article-title":"Genome\u2010wide DNA Methylation Profiling of Peripheral Blood Reveals an Epigenetic Signature Associated with Severe COVID\u201019","volume":"110","author":"Corley","year":"2021","journal-title":"J. Leukoc. Bio"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1056\/nejmc2103916","article-title":"Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19","volume":"384","author":"Doria-Rose","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"101167","DOI":"10.1016\/j.arr.2020.101167","article-title":"The Geroscience Agenda: Toxic Stress, Hormetic Stress, and the Rate of Aging","volume":"63","author":"Epel","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"9306","DOI":"10.3390\/ijms22179306","article-title":"Epigenetic Clocks Are Not Accelerated in COVID-19 Patients","volume":"22","author":"Franzen","year":"2021","journal-title":"Ijms"},{"key":"B21","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.exger.2018.01.019","article-title":"Responders and Non-responders to Influenza Vaccination: A DNA Methylation Approach on Blood Cells","volume":"105","author":"Gensous","year":"2018","journal-title":"Exp. Gerontol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"e1003007","DOI":"10.1371\/journal.ppat.1003007","article-title":"Epigenetics of Host-Pathogen Interactions: the Road Ahead and the Road behind","volume":"8","author":"G\u00f3mez-D\u00edaz","year":"2012","journal-title":"PLoS Pathog."},{"key":"B23","doi-asserted-by":"publisher","first-page":"465725","DOI":"10.1101\/2021.10.25.465725","article-title":"Ultra-cheap and Scalable Epigenetic Age Predictions with TIME-Seq","volume":"25","author":"Griffin","year":"20212021","journal-title":"bioRxiv"},{"key":"B24","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","article-title":"Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates","volume":"49","author":"Hannum","year":"2013","journal-title":"Mol. Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.semcdb.2021.01.003","article-title":"Aging Biomarkers and the Brain","volume":"116","author":"Higgins-Chen","year":"","journal-title":"Seminars Cell & Dev. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"440205","DOI":"10.1101\/2021.04.16.440205","article-title":"A Computational Solution for Bolstering Reliability of Epigenetic Clocks: Implications for Clinical Trials and Longitudinal Tracking","volume":"16","author":"Higgins-Chen","year":"","journal-title":"bioRxiv"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3806","DOI":"10.1038\/s41380-019-0616-9","article-title":"An Epigenetic Predictor of Death Captures Multi-Modal Measures of Brain Health","volume":"26","author":"Hillary","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13148-020-00905-6","article-title":"Epigenetic Measures of Ageing Predict the Prevalence and Incidence of Leading Causes of Death and Disease Burden","volume":"12","author":"Hillary","year":"2020","journal-title":"Clin. Epigenet"},{"key":"B29","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA Methylation Age of Human Tissues and Cell Types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1093\/infdis\/jiv277","article-title":"HIV-1 Infection Accelerates Age According to the Epigenetic Clock","volume":"212","author":"Horvath","year":"2015","journal-title":"J. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.18632\/aging.101508","article-title":"Epigenetic Clock for Skin and Blood Cells Applied to Hutchinson Gilford Progeria Syndrome and Ex Vivo Studies","volume":"10","author":"Horvath","year":"2018","journal-title":"Aging"},{"key":"B32","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA Methylation-Based Biomarkers and the Epigenetic Clock Theory of Ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1471-2105-13-86","article-title":"DNA Methylation Arrays as Surrogate Measures of Cell Mixture Distribution","volume":"13","author":"Houseman","year":"2012","journal-title":"BMC Bioinforma."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1101\/2021.07.05.21260014","article-title":"Epigenome-wide DNA Methylation Profiling of Healthy COVID-19 Recoverees Reveals a Unique Signature in Circulating Immune Cells","author":"Huoman","year":"2021","journal-title":"bioRxiv"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-28582\/v1","article-title":"The COVID-19 Gene and Drug Set Library","author":"Kuleshov","year":"2020","journal-title":"Res. Sq."},{"key":"B36","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.10.20147777","article-title":"COVID-19 Severity Is Predicted by Earlier Evidence of Accelerated Aging","author":"Kuo","year":"2020","journal-title":"medRxiv"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e84","DOI":"10.1056\/NEJMoa2114583","article-title":"Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months","volume":"385","author":"Levin","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"573","DOI":"10.18632\/aging.101414","article-title":"An Epigenetic Biomarker of Aging for Lifespan and Healthspan","volume":"10","author":"Levine","year":"2018","journal-title":"Aging"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e13229","DOI":"10.1111\/acel.13229","article-title":"Underlying Features of Epigenetic Aging Clocks In Vivo and In Vitro","volume":"19","author":"Liu","year":"2020","journal-title":"Aging Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.2217\/epi-2017-0078","article-title":"The Correlation of Methylation Levels Measured Using Illumina 450K and EPIC BeadChips in Blood Samples","volume":"9","author":"Logue","year":"2017","journal-title":"Epigenomics"},{"key":"B42","doi-asserted-by":"publisher","first-page":"303","DOI":"10.18632\/aging.101684","article-title":"DNA Methylation GrimAge Strongly Predicts Lifespan and Healthspan","volume":"11","author":"Lu","year":"2019","journal-title":"Aging"},{"key":"B44","doi-asserted-by":"publisher","first-page":"6151","DOI":"10.1101\/2021.04.23.21255973","article-title":"Evidence for Biological Age Acceleration and Telomere Shortening in Covid19 Survivors","volume":"22","author":"Mongelli","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trsl.2018.08.001","article-title":"DNA Methylation as a Transcriptional Regulator of the Immune System","volume":"204","author":"Morales-Nebreda","year":"2019","journal-title":"Transl. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"9959","DOI":"10.18632\/aging.103344","article-title":"Why Does COVID-19 Disproportionately Affect Older People?","volume":"12","author":"Mueller","year":"2020","journal-title":"Aging"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1093\/infdis\/jiv202","article-title":"Telomere Length as an Indicator of the Robustness of B- and T-Cell Response to Influenza in Older Adults","volume":"212","author":"Najarro","year":"2015","journal-title":"J. Infect. Dis."},{"key":"B48","first-page":"100249","article-title":"Effectiveness of Heterologous ChAdOx1 nCoV-19 and mRNA Prime-Boost Vaccination against Symptomatic Covid-19 Infection in Sweden: A Nationwide Cohort Study","volume-title":"The Lancet Regional Health-Europe","author":"Nordstr\u00f6m","year":"2021"},{"key":"B49","doi-asserted-by":"publisher","first-page":"101348","DOI":"10.1016\/j.arr.2021.101348","article-title":"A Systematic Review of Biological, Social and Environmental Factors Associated with Epigenetic Clock Acceleration","volume":"69","author":"Oblak","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"B50","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s13059-016-1066-1","article-title":"Critical Evaluation of the Illumina MethylationEPIC BeadChip Microarray for Whole-Genome DNA Methylation Profiling","volume":"17","author":"Pidsley","year":"2016","journal-title":"Genome Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1111\/all.14907","article-title":"Caspases and Therapeutic Potential of Caspase Inhibitors in Moderate-Severe SARS\u2010CoV\u20102 Infection and Long COVID","volume":"77","author":"Plassmeyer","year":"2021","journal-title":"Allergy"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/nejmoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41586-021-04120-y","article-title":"Immunogenicity and Efficacy of Heterologous ChAdOx1-BNT162b2 Vaccination","volume":"600","author":"Pozzetto","year":"2021","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1016\/j.cmet.2021.09.009","article-title":"Hyperglycemia in Acute COVID-19 Is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2","volume":"33","author":"Reiterer","year":"2021","journal-title":"Cell Metab."},{"key":"B55","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/s41586-021-03475-6","article-title":"The Spatial Landscape of Lung Pathology during COVID-19 Progression","volume":"593","author":"Rendeiro","year":"2021","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/43678","article-title":"Acinus Is a Caspase-3-Activated Protein Required for Apoptotic Chromatin Condensation","volume":"401","author":"Sahara","year":"1999","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/pathogens6010008","article-title":"Epigenetic Landscape during Coronavirus Infection","volume":"6","author":"Sch\u00e4fer","year":"2017","journal-title":"Pathogens"},{"key":"B58","doi-asserted-by":"publisher","first-page":"3990","DOI":"10.1111\/ajt.16818","article-title":"Cellular Immunity Predominates over Humoral Immunity after Homologous and Heterologous mRNA and Vector\u2010based COVID\u201019 Vaccine Regimens in Solid Organ Transplant Recipients","volume":"21","author":"Schmidt","year":"2021","journal-title":"Am. J. Transpl."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1016\/s0140-6736(21)01115-6","article-title":"Heterologous Prime-Boost COVID-19 Vaccination: Initial Reactogenicity Data","volume":"397","author":"Shaw","year":"2021","journal-title":"Lancet"},{"key":"B60","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1093\/ageing\/afaa274","article-title":"Efficacy and Safety of COVID-19 Vaccines in Older People","volume":"50","author":"Soiza","year":"2021","journal-title":"Age Ageing"},{"key":"B61","doi-asserted-by":"publisher","first-page":"100014","DOI":"10.1016\/j.patter.2020.100014","article-title":"Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement","volume":"1","author":"Sugden","year":"2020","journal-title":"Patterns"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/S0140-6736(21)02183-8","article-title":"Effectiveness of mRNA BNT162b2 COVID-19 Vaccine up to 6 Months in a Large Integrated Health System in the USA: a Retrospective Cohort Study","volume":"398","author":"Tartof","year":"2021","journal-title":"The Lancet"},{"key":"B63","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.1093\/bioinformatics\/btx513","article-title":"ChAMP: Updated Methylation Analysis Pipeline for Illumina BeadChips","volume":"33","author":"Tian","year":"2017","journal-title":"Bioinformatics"},{"key":"B64","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41586-021-03738-2","article-title":"SARS-CoV-2 mRNA Vaccines Induce Persistent Human Germinal Centre Responses","volume":"596","author":"Turner","year":"2021","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/s41591-020-0944-y","article-title":"A Single-Cell Atlas of the Peripheral Immune Response in Patients with Severe COVID-19","volume":"26","author":"Wilk","year":"2020","journal-title":"Nat. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1016\/j.cell.2021.05.039","article-title":"The Single-Cell Epigenomic and Transcriptional Landscape of Immunity to Influenza Vaccination","volume":"184","author":"Wimmers","year":"2021","journal-title":"Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s13059-016-1064-3","article-title":"Correlation of an Epigenetic Mitotic Clock with Cancer Risk","volume":"17","author":"Yang","year":"2016","journal-title":"Genome Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1038\/s41590-021-00979-1","article-title":"Epigenetic Scars of CD8+ T Cell Exhaustion Persist after Cure of Chronic Infection in Humans","volume":"22","author":"Yates","year":"2021","journal-title":"Nat. Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1093\/bioinformatics\/btz833","article-title":"EpiDISH Web Server: Epigenetic Dissection of Intra-sample-heterogeneity with Online GUI","volume":"36","author":"Zheng","year":"2019","journal-title":"Bioinformatics"},{"key":"B70","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/ahg.12440","article-title":"An Epigenome\u2010wide DNA Methylation Study of Patients with COVID\u201019","volume":"85","author":"Zhou","year":"2021","journal-title":"Ann. Hum. Genet."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1093\/nar\/gky691","article-title":"SeSAMe: Reducing Artifactual Detection of DNA Methylation by Infinium BeadChips in Genomic Deletions","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.819749\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T02:35:09Z","timestamp":1654223709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.819749\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":70,"alternative-id":["10.3389\/fgene.2022.819749"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.819749","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.01.21266670","asserted-by":"object"}]},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,3]]},"article-number":"819749"}}