{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:47:34Z","timestamp":1769842054846,"version":"3.49.0"},"reference-count":111,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM133658"],"award-info":[{"award-number":["R35GM133658"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG066749"],"award-info":[{"award-number":["R01AG066749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM137836"],"award-info":[{"award-number":["R35GM137836"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chan Zuckerberg Initiative, Research Corporation for Science Advancement","award":["# 28706"],"award-info":[{"award-number":["# 28706"]}]},{"name":"Cottrell Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) is one of the most challenging neurodegenerative diseases because of its complicated and progressive mechanisms, and multiple risk factors. Increasing research evidence demonstrates that genetics may be a key factor responsible for the occurrence of the disease. Although previous reports identified quite a few AD-associated genes, they were mostly limited owing to patient sample size and selection bias. There is a lack of comprehensive research aimed to identify AD-associated risk mutations systematically. To address this challenge, we hereby construct a large-scale AD mutation and co-mutation framework (\u2018AD-Syn-Net\u2019), and propose deep learning models named Deep-SMCI and Deep-CMCI configured with fully connected layers that are capable of predicting cognitive impairment of subjects effectively based on genetic mutation and co-mutation profiles. Next, we apply the customized frameworks to data sets to evaluate the importance scores of the mutations and identified mutation effectors and co-mutation combination vulnerabilities contributing to cognitive impairment. Furthermore, we evaluate the influence of mutation pairs on the network architecture to dissect the genetic organization of AD and identify novel co-mutations that could be responsible for dementia, laying a solid foundation for proposing future targeted therapy for AD precision medicine. Our deep learning model codes are available open access here: https:\/\/github.com\/Pan-Bio\/AD-mutation-effectors.<\/jats:p>","DOI":"10.1093\/bib\/bbad030","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T22:18:35Z","timestamp":1675721915000},"source":"Crossref","is-referenced-by-count":4,"title":["AD-Syn-Net: systematic identification of Alzheimer\u2019s disease-associated mutation and co-mutation vulnerabilities via deep learning"],"prefix":"10.1093","volume":"24","author":[{"given":"Xingxin","family":"Pan","sequence":"first","affiliation":[{"name":"Livestrong Cancer Institutes , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"},{"name":"The University of Texas at Austin , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeynep H","family":"Coban Akdemir","sequence":"additional","affiliation":[{"name":"Human Genetics Center , Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, , Houston, TX 77030 , USA"},{"name":"The University of Texas Health Science Center at Houston , Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, , Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biological Sciences, University of Illinois Chicago , Chicago, IL 60607 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqian","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Biomedical Informatics, University of Texas Health Science Center , Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria M","family":"Sheynkman","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia , Charlottesville, VA 22903 , USA"},{"name":"Department of Biochemistry and Molecular Genetics , School of Medicine, , Charlottesville, VA 22903 , USA"},{"name":"University of Virginia , School of Medicine, , Charlottesville, VA 22903 , USA"},{"name":"Center for Public Health Genomics , and UVA Comprehensive Cancer Center, , Charlottesville, VA 22903 , USA"},{"name":"University of Virginia , and UVA Comprehensive Cancer Center, , Charlottesville, VA 22903 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erxi","family":"Wu","sequence":"additional","affiliation":[{"name":"Livestrong Cancer Institutes , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"},{"name":"The University of Texas at Austin , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"},{"name":"Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health , Temple, TX 76502 , USA"},{"name":"Department of Surgery , Texas A & M University Health Science Center, , Temple, TX 76508 , USA"},{"name":"College of Medicine , Texas A & M University Health Science Center, , Temple, TX 76508 , USA"},{"name":"Department of Pharmaceutical Sciences , Texas A & M University Health Science Center, College of Pharmacy, , TX 77843 , USA"},{"name":"College Station , Texas A & M University Health Science Center, College of Pharmacy, , TX 77843 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason H","family":"Huang","sequence":"additional","affiliation":[{"name":"Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health , Temple, TX 76502 , USA"},{"name":"Department of Surgery , Texas A & M University Health Science Center, , Temple, TX 76508 , USA"},{"name":"College of Medicine , Texas A & M University Health Science Center, , Temple, TX 76508 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidhi","family":"Sahni","sequence":"additional","affiliation":[{"name":"Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center , Houston, TX 77054 , USA"},{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 , USA"},{"name":"Quantitative and Computational Biosciences Program, Baylor College of Medicine , Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-8103","authenticated-orcid":false,"given":"S Stephen","family":"Yi","sequence":"additional","affiliation":[{"name":"Livestrong Cancer Institutes , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"},{"name":"The University of Texas at Austin , and Department of Oncology, Dell Medical School, , Austin, TX 78712 , USA"},{"name":"Oden Institute for Computational Engineering and Sciences (ICES), The University of Texas at Austin , Austin, TX 78712 , USA"},{"name":"Interdisciplinary Life Sciences Graduate Programs (ILSGP) , College of Natural Sciences, , Austin, TX 78712 , USA"},{"name":"The University of Texas at Austin , College of Natural Sciences, , Austin, TX 78712 , USA"},{"name":"Department of Biomedical Engineering , Cockrell School of Engineering, , Austin, TX 78712 , USA"},{"name":"The University of Texas at Austin , Cockrell School of Engineering, , Austin, TX 78712 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"2023032004364367600_","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1002\/anie.200802808","article-title":"Alzheimer\u2019s disease: from pathology to therapeutic approaches","volume":"48","author":"Jakob-Roetne","year":"2009","journal-title":"Angew Chem Int 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