{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:53:11Z","timestamp":1778633591170,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["91540114"],"award-info":[{"award-number":["91540114"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["31671342"],"award-info":[{"award-number":["31671342"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["31871331"],"award-info":[{"award-number":["31871331"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["31271398"],"award-info":[{"award-number":["31271398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>RNA 5-methylcytosine (m5C) is a type of post-transcriptional modification that may be involved in numerous biological processes and tumorigenesis. RNA m5C can be profiled at single-nucleotide resolution by high-throughput sequencing of RNA treated with bisulfite (RNA-BisSeq). However, the exploration of transcriptome-wide profile and potential function of m5C in splicing remains to be elucidated due to lack of isoform level m5C quantification tool.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We developed a computational package to quantify Epitranscriptomal RNA m5C at the transcript isoform level (named Episo). Episo consists of three tools: mapper, quant and Bisulfitefq, for mapping, quantifying and simulating RNA-BisSeq data, respectively. The high accuracy of Episo was validated using an improved m5C-specific methylated RNA immunoprecipitation (meRIP) protocol, as well as a set of in silico experiments. By applying Episo to public human and mouse RNA-BisSeq data, we found that the RNA m5C is not evenly distributed among the transcript isoforms, implying the m5C may subject to be regulated at isoform level.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Episo is released under the GNU GPLv3+ license. The resource code Episo is freely accessible from https:\/\/github.com\/liujunfengtop\/Episo (with Tophat\/cufflink) and https:\/\/github.com\/liujunfengtop\/Episo\/tree\/master\/Episo_Kallisto (with Kallisto).<\/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\/btz900","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T12:11:10Z","timestamp":1575029470000},"page":"2033-2039","source":"Crossref","is-referenced-by-count":6,"title":["Episo: quantitative estimation of RNA 5-methylcytosine at isoform level by high-throughput sequencing of RNA treated with bisulfite"],"prefix":"10.1093","volume":"36","author":[{"given":"Junfeng","family":"Liu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyang","family":"An","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"School of Life Science, University of Chinese Academy of Sciences , Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifei","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"School of Life Science, University of Chinese Academy of Sciences , Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"key":"2023062312014052600_btz900-B1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1261\/rna.050575.115","article-title":"The importance of being modified: an unrealized code to RNA structure and function","volume":"21","author":"Agris","year":"2015","journal-title":"RNA"},{"key":"2023062312014052600_btz900-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-016-1139-1","article-title":"Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain","volume":"18","author":"Amort","year":"2017","journal-title":"Genome Biol"},{"key":"2023062312014052600_btz900-B3","doi-asserted-by":"crossref","first-page":"W202","DOI":"10.1093\/nar\/gkp335","article-title":"MEME SUITE: tools for motif discovery and searching","volume":"37","author":"Bailey","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023062312014052600_btz900-B4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of alternative pre-messenger RNA splicing","volume":"72","author":"Black","year":"2003","journal-title":"Annu. 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