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We characterized gene\u2010expression patterns at the mild cognitive impairment (MCI) stage to identify critical mRNA measures and gene clusters associated with AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a transcriptomics approach, integrating magnetic resonance imaging (MRI) and peripheral blood\u2010based gene expression data using persistent homology (PH) followed by kernel\u2010based clustering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified three clusters of genes significantly associated with diagnosis of amnestic MCI. The biological processes associated with each cluster were mitochondrial function, NF\u2010kB signaling, and apoptosis. Cluster\u2010level associations with cortical thickness displayed canonical AD\u2010like patterns. Driver genes from clusters were also validated in an external dataset for prediction of amyloidosis and clinical diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We found a disease\u2010relevant transcriptomic signature sensitive to prodromal AD and identified a subset of potential therapeutic targets associated with AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12587","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:03:41Z","timestamp":1644451421000},"page":"2493-2508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of gene expression patterns in mild cognitive impairment using a transcriptomics approach and neuroimaging endophenotypes"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-0587","authenticated-orcid":false,"given":"Apoorva","family":"Bharthur Sanjay","sequence":"first","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Patania","sequence":"additional","affiliation":[{"name":"Indiana University Network Sciences Institute Indiana University  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Yan","sequence":"additional","affiliation":[{"name":"Indiana University Network Sciences Institute Indiana University  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Svaldi","sequence":"additional","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugce","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology &amp; Geriatric Medicine Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nemes","sequence":"additional","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana G.","family":"Apostolova","sequence":"additional","affiliation":[{"name":"Department of Neurology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.117"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0311-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610204104"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12393"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516604113"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170205"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-101521"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-101518"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.02.084"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.12.007"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.06.032"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00454\u2010002\u20102885\u20102"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-7687-1_511"},{"key":"e_1_2_8_16_1","first-page":"2211","article-title":"Multiple kernel learning algorithms","volume":"12","author":"G\u00f6nen M","year":"2011","journal-title":"J Mach Lear Res"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","unstructured":"ReininghausJ HuberS BauerU&KwittR.A stable multi\u2010scale kernel for topological machine learning. 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