{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:48:57Z","timestamp":1783698537276,"version":"3.55.0"},"reference-count":114,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31671373"],"award-info":[{"award-number":["31671373"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"XJTLU Key Program Special Fund","award":["KSF-T-01"],"award-info":[{"award-number":["KSF-T-01"]}]},{"name":"XJTLU Key Program Special Fund","award":["KSF-P-02"],"award-info":[{"award-number":["KSF-P-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation N6-methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. Evidence increasingly demonstrates its crucial importance in essential molecular mechanisms and various diseases. With recent advances in sequencing techniques, tens of thousands of m6A sites are identified in a typical high-throughput experiment, posing a key challenge to distinguish the functional m6A sites from the remaining \u2018passenger\u2019 (or \u2018silent\u2019) sites. Results: We performed a comparative conservation analysis of the human and mouse m6A epitranscriptomes at single site resolution. A novel scoring framework, ConsRM, was devised to quantitatively measure the degree of conservation of individual m6A sites. ConsRM integrates multiple information sources and a positive-unlabeled learning framework, which integrated genomic and sequence features to trace subtle hints of epitranscriptome layer conservation. With a series validation experiments in mouse, fly and zebrafish, we showed that ConsRM outperformed well-adopted conservation scores (phastCons and phyloP) in distinguishing the conserved and unconserved m6A sites. Additionally, the m6A sites with a higher ConsRM score are more likely to be functionally important. An online database was developed containing the conservation metrics of 177\u00a0998 distinct human m6A sites to support conservation analysis and functional prioritization of individual m6A sites. And it is freely accessible at: https:\/\/www.xjtlu.edu.cn\/biologicalsciences\/con.<\/jats:p>","DOI":"10.1093\/bib\/bbab088","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T12:17:33Z","timestamp":1614341853000},"source":"Crossref","is-referenced-by-count":50,"title":["ConsRM: collection and large-scale prediction of the evolutionarily conserved RNA methylation sites, with implications for the functional epitranscriptome"],"prefix":"10.1093","volume":"22","author":[{"given":"Bowen","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education of Gastrointestinal Cancer, School of Basic Medical Science, Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong-Liverpool University, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Xi\u2019an Jiaotong-Liverpool University, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jionglong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences, Xi\u2019an Jiaotong-Liverpool University, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"de Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Institute of Ageing & Chronic Disease, University of Liverpool, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Rigden","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Xi\u2019an Jiaotong-Liverpool University, L7 8TX, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"issue":"1","key":"2021110814192305800_ref1","doi-asserted-by":"crossref","first-page":"e1618","DOI":"10.1002\/wrna.1618","article-title":"A birds'-eye view of the activity and specificity of the mRNA m(6) a methyltransferase complex","volume":"12","author":"Garcias Morales","year":"2021","journal-title":"Wiley Interdiscip Rev 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O'Donnell, An open access database of genome-wide association results","volume":"10","author":"Johnson","year":"2009","journal-title":"BMC Med Genet"},{"issue":"D1","key":"2021110814192305800_ref98","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2021110814192305800_ref99","doi-asserted-by":"crossref","first-page":"D92","DOI":"10.1093\/nar\/gkt1248","article-title":"starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein\u2013RNA interaction networks from large-scale CLIP-Seq data","volume":"42","author":"Li","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2021110814192305800_ref100","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13059-016-0924-1","article-title":"JBrowse: a dynamic web platform for genome visualization and 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