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We identified networks of differentially co\u2010expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242\u2010gene subnetwork enriched for independent AD\/HD signatures. This subnetwork revealed a surprising dichotomy of gained\/lost correlations among two inter\u2010connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases,\n                    <jats:italic>DNMT1<\/jats:italic>\n                    and\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    , of which we predicted the former but not latter as a key regulator. To validate the inter\u2010connection of these two processes and our key regulator prediction, we generated two brain\u2010specific knockout (KO) mice and show that\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    KO signature significantly overlaps with the subnetwork (\n                    <jats:italic>P<\/jats:italic>\n                    = 3.1\u00a0\u00d7\u00a010\n                    <jats:sup>\u221212<\/jats:sup>\n                    ), while\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    KO signature does not (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.017).\n                  <\/jats:p>","DOI":"10.15252\/msb.20145304","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T03:52:28Z","timestamp":1406778748000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":205,"title":["Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases"],"prefix":"10.1038","volume":"10","author":[{"given":"Manikandan","family":"Narayanan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy L","family":"Huynh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyeul","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"McElwee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunsheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Lamb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Suver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliona","family":"Molony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Melquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E","family":"Schadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Casaccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valur","family":"Emilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,30]]},"reference":[{"key":"BFMSB145304_CR1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1528-1167.2006.00554.x","volume":"47","author":"JC Amatniek","year":"2006","unstructured":"Amatniek JC, Hauser WA, DelCastillo\u2010Castaneda C, Jacobs DM, Marder K, Bell K, Albert M, Brandt J, Stern Y (2006) Incidence and predictors of seizures in patients with Alzheimer's disease. 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