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Dementia"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Recent studies revealed the association of abnormal methylomic changes with Alzheimer's disease (AD) but there is a lack of systematic study of the impact of methylomic alterations over the molecular networks underlying AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We profiled genome\u2010wide methylomic variations in the parahippocampal gyrus from 201\n                      <jats:italic>post mortem<\/jats:italic>\n                      control, mild cognitive impaired, and AD brains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified 270 distinct differentially methylated regions (DMRs) associated with AD. We quantified the impact of these DMRs on each gene and each protein as well as gene and protein co\u2010expression networks. DNA methylation had a\u00a0profound impact on both AD\u2010associated gene\/protein modules and their key regulators. We further integrated the matched multi\u2010omics data to show the impact of DNA methylation on chromatin accessibility, which further modulates gene and protein expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The quantified impact of DNA methylation on gene and protein networks underlying AD identified potential upstream epigenetic regulators of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            A cohort of DNA methylation data in the parahippocampal gyrus was developed from 201\n                            <jats:italic>post mortem<\/jats:italic>\n                            control, mild cognitive impaired, and Alzheimer's disease (AD) brains.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Two hundred seventy distinct differentially methylated regions (DMRs) were found to be associated with AD compared to normal control.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A metric was developed to quantify methylation impact on each gene and each protein.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>DNA methylation was found to have a\u00a0profound impact on not only the AD\u2010associated gene modules but also key regulators of the gene and protein networks.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Key findings were validated in an independent multi\u2010omics cohort in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The impact of DNA methylation on chromatin accessibility was also investigated by integrating the matched methylomic, epigenomic, transcriptomic, and proteomic data.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12969","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T07:04:18Z","timestamp":1677049458000},"page":"3472-3495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genome\u2010wide methylomic regulation of multiscale gene networks in Alzheimer's 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