{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:39:19Z","timestamp":1770338359350,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T00:00:00Z","timestamp":1485475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81274118"],"award-info":[{"award-number":["81274118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key New Drug Creation and Development Program of China","award":["2012ZX09103-201"],"award-info":[{"award-number":["2012ZX09103-201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The pathogenesis of AD is complex and contributed by both genetic and environmental factors. Recent work revealed a potential link between DNA methylation and AD. However, a genome-wide study to identify potential DNA methylation sites involved in AD is still at an early stage. WGBS, an up-to-date technology, was used in this study. We investigated mouse brain genome-wide DNA methylation profiles between seven-month-old SAMP8 and SAMR1 models through deep WGBS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>According to the results, the global ML slightly decreased in the SAMP8 mice than in the SAMR1 mice (4.12% versus 4.19%). A total of 1 307 172 280 clean reads were obtained. Subsequently, we identified 63 DMRs from all cases in SAMP8 mice relative to SAMR1 mice. In addition, 26 DMR-related genes were detected. GO analyses revealed that these DMR-related genes were involved in regulating the development of AD from different aspects. Finally, three differentially expressed DMR-related genes (Dlgap1, TMEM51 and Eif2ak2) that were most likely involved in AD were summarized and listed in detail. Our study provided a systematic exploration of DNA methylation profiles in SAMP8 mouse brain for the first time. These novel methylation sites may be considered strong future candidates to combat this life-threatening disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>The WGBS sequencing clean data and RNA-seq clean data have been deposited in the NCBI Sequence Read Archive (SRA).The accession number of WGBS is SRP097054. The accession number of RNA-seq is SRP096779.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx040","type":"journal-article","created":{"date-parts":[[2017,1,28]],"date-time":"2017-01-28T01:25:31Z","timestamp":1485566731000},"page":"1591-1595","source":"Crossref","is-referenced-by-count":34,"title":["Genome-wide analysis of DNA methylation profiles in a senescence-accelerated mouse prone 8 brain using whole-genome bisulfite sequencing"],"prefix":"10.1093","volume":"33","author":[{"given":"Shuai","family":"Zhang","sequence":"first","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"}]},{"given":"Chunxia","family":"Qin","sequence":"additional","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"}]},{"given":"Guoqiong","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"}]},{"given":"Limin","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"}]},{"given":"Chengqiang","family":"Feng","sequence":"additional","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"}]},{"given":"Wensheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China"},{"name":"Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China"},{"name":"College of Resources Science Technology, Beijing Normal University, Beijing, China"},{"name":"National and Local United Engineering Research Center for Sanqi Resources Protection and Utilization Technology, Kunming, China"}]}],"member":"286","published-online":{"date-parts":[[2017,1,27]]},"reference":[{"key":"2023020205301245200_btx040-B1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3233\/JAD-2012-111223","article-title":"Genome-wide DNA methylation differences between late-onset Alzheimer's disease and cognitively normal controls in human frontal cortex","volume":"29","author":"Bakulski","year":"2012","journal-title":"J. Alzheimers Dis"},{"key":"2023020205301245200_btx040-B2","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/brain\/awh193","article-title":"Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population","volume":"127","author":"Barton","year":"2004","journal-title":"Brain"},{"key":"2023020205301245200_btx040-B3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mad.2008.12.003","article-title":"Decline in genomic DNA methylation through aging in a cohort of elderly subjects","volume":"130","author":"Bollati","year":"2009","journal-title":"Mech. Ageing Dev"},{"key":"2023020205301245200_btx040-B4","doi-asserted-by":"crossref","first-page":"b158.","DOI":"10.1136\/bmj.b158","article-title":"Alzheimer's disease","volume":"338","author":"Burns","year":"2009","journal-title":"BMJ"},{"key":"2023020205301245200_btx040-B5","doi-asserted-by":"crossref","first-page":"8489.","DOI":"10.1038\/srep08489","article-title":"Neuroinflammation and A\u03b2 accumulation linked to systemic inflammation are decreased by genetic PKR down-regulation","volume":"5","author":"Carret-Rebillat","year":"2015","journal-title":"Sci. Rep"},{"key":"2023020205301245200_btx040-B6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/ilar.38.1.41","article-title":"Special Report: The 1996 Guide for the Care and Use of Laboratory Animals","volume":"38","author":"Clark","year":"1997","journal-title":"ILAR J. Natl. Res. Council Inst. Lab. Anim. Resour"},{"key":"2023020205301245200_btx040-B7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature06745","article-title":"Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning","volume":"452","author":"Cokus","year":"2008","journal-title":"Nature"},{"key":"2023020205301245200_btx040-B8","doi-asserted-by":"crossref","first-page":"215.","DOI":"10.1186\/1471-2105-15-215","article-title":"Using beta-binomial regression for high-precision differential methylation analysis in multifactor whole-genome bisulfite sequencing experiments","volume":"15","author":"Dolzhenko","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2023020205301245200_btx040-B9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nn.3607","article-title":"Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain","volume":"17","author":"Guo","year":"2014","journal-title":"Nat. Neurosci"},{"key":"2023020205301245200_btx040-B10","doi-asserted-by":"crossref","first-page":"6701","DOI":"10.1039\/C4CS00026A","article-title":"Metal complexes designed to bind to amyloid-\u03b2 for the diagnosis and treatment of Alzheimer's disease","volume":"43","author":"Hayne","year":"2014","journal-title":"Chem. Soc. Rev"},{"key":"2023020205301245200_btx040-B11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/cr.2011.23","article-title":"Regulation and function of DNA methylation in plants and animals","volume":"21","author":"He","year":"2011","journal-title":"Cell Res"},{"key":"2023020205301245200_btx040-B12","doi-asserted-by":"crossref","first-page":"6546.","DOI":"10.1038\/srep06546","article-title":"Genome-wide DNA methylation profiles and their relationships with mRNA and the microRNA transcriptome in bovine muscle tissue (Bos taurine)","volume":"4","author":"Huang","year":"2014","journal-title":"Sci. Rep"},{"key":"2023020205301245200_btx040-B13","doi-asserted-by":"crossref","first-page":"653.","DOI":"10.1186\/1471-2164-15-653","article-title":"Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs","volume":"15","author":"Jin","year":"2013","journal-title":"BMC Genomics"},{"key":"2023020205301245200_btx040-B14","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.yhbeh.2014.03.017","article-title":"Dihydrotestosterone treatment delays the conversion from mild cognitive impairment to Alzheimer's disease in SAMP8 mice","volume":"65","author":"Kang","year":"2014","journal-title":"Horm. Behav"},{"key":"2023020205301245200_btx040-B15","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1073\/pnas.1411269112","article-title":"Reading the unique DNA methylation landscape of the brain: non-CpG methylation, hydroxymethylation, and MeCP2","volume":"112","author":"Kinde","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"2023020205301245200_btx040-B16","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3233\/JAD-142919","article-title":"Distinct expression of long non-coding RNAs in an Alzheimer's disease model","volume":"45","author":"Lee","year":"2015","journal-title":"J. Alzheimers Dis"},{"key":"2023020205301245200_btx040-B17","doi-asserted-by":"crossref","first-page":"85.","DOI":"10.3389\/fnagi.2013.00085","article-title":"DNA methylation, a hand behind neurodegenerative diseases","volume":"5","author":"Lu","year":"2013","journal-title":"Front. Aging Neurosci"},{"key":"2023020205301245200_btx040-B18","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.neurobiolaging.2008.12.005","article-title":"Epigenetic changes in Alzheimer's disease: decrements in DNA methylation","volume":"31","author":"Mastroeni","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"2023020205301245200_btx040-B19","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1172\/JCI80825","article-title":"MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia","volume":"126","author":"Riedel","year":"2016","journal-title":"J. Clin. Invest"},{"key":"2023020205301245200_btx040-B20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.2174\/156720509788486644","article-title":"The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects","volume":"6","author":"Rocchi","year":"2009","journal-title":"Curr. Alzheimer Res"},{"key":"2023020205301245200_btx040-B21","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1093\/brain\/awt237","article-title":"DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease","volume":"136","author":"Sanchez-Mut","year":"2013","journal-title":"Brain"},{"key":"2023020205301245200_btx040-B22","doi-asserted-by":"crossref","first-page":"11943","DOI":"10.1074\/jbc.272.18.11943","article-title":"SAPAPs. A family of PSD-95\/SAP90-associated proteins localized at postsynaptic density","volume":"272","author":"Takeuchi","year":"1997","journal-title":"J. Biol. Chem"},{"key":"2023020205301245200_btx040-B23","doi-asserted-by":"crossref","first-page":"23259.","DOI":"10.1038\/srep23259","article-title":"The DmtA methyltransferase contributes to Aspergillus flavus conidiation, sclerotial production, aflatoxin biosynthesis and virulence","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep"},{"key":"2023020205301245200_btx040-B24","doi-asserted-by":"crossref","first-page":"R14.","DOI":"10.1186\/gb-2010-11-2-r14","article-title":"Gene ontology analysis for RNA-seq: accounting for selection bias","volume":"11","author":"Young","year":"2010","journal-title":"Genome Biol"},{"key":"2023020205301245200_btx040-B25","doi-asserted-by":"crossref","first-page":"22138.","DOI":"10.1038\/srep22138","article-title":"Profiling the genome-wide DNA methylation pattern of porcine ovaries using reduced representation bisulfite sequencing","volume":"6","author":"Yuan","year":"2016","journal-title":"Sci. Rep"},{"key":"2023020205301245200_btx040-B26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cell.2011.11.050","article-title":"Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis","volume":"148","author":"Zhang","year":"2012","journal-title":"Cell"},{"key":"2023020205301245200_btx040-B27","doi-asserted-by":"crossref","first-page":"e19.","DOI":"10.1093\/nar\/gkv906","article-title":"A computational method for studying the relation between alternative splicing and DNA methylation","volume":"44","author":"Zheng","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023020205301245200_btx040-B28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11596-007-0316-6","article-title":"Re-expression of RASSF1A by 5-Aza-CdR induced demethylation of the promoter region in human biliary tract carcinoma cells","volume":"27","author":"Zuo","year":"2007","journal-title":"J. Huazhong Univ. Sci. Technol. Med. Sci"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/11\/1591\/49039787\/bioinformatics_33_11_1591.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/11\/1591\/49039787\/bioinformatics_33_11_1591.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T05:31:29Z","timestamp":1675315889000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/33\/11\/1591\/2959851"}},"subtitle":[],"editor":[{"given":"John","family":"Hancock","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2017,1,27]]},"references-count":28,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btx040","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,6,1]]},"published":{"date-parts":[[2017,1,27]]}}}