{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:11Z","timestamp":1753875791741,"version":"3.41.2"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Chinese National Natural Science Foundation","doi-asserted-by":"crossref","award":["82173383"],"award-info":[{"award-number":["82173383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Identifying chromatin accessibility is one of the key steps in studying the regulation of eukaryotic genomes. The combination of exogenous methyltransferase and nanopore sequencing provides an strategy to identify open chromatin over long genomic ranges at the single-molecule scale. However, endogenous methylation, non-open-chromatin-specific exogenous methylation and base-calling errors limit the accuracy and hinders its application to complex genomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We systematically evaluated the impact of these three influence factors, and developed a model-based computational method, methyltransferase accessible genome region finder (MAGNIFIER), to address the issues. By incorporating control data, MAGNIFIER attenuates the three influence factors with data-adaptive comparison strategy. We demonstrate that MAGNIFIER is not only sensitive to identify the open chromatin with much improved accuracy, but also able to detect the chromatin accessibility of repetitive regions that are missed by NGS-based methods. By incorporating long-read RNA-seq data, we revealed the association between the accessible Alu elements and non-classic gene isoforms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Freely available on web at https:\/\/github.com\/Goatofmountain\/MAGNIFIER.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae206","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T20:24:05Z","timestamp":1713039845000},"source":"Crossref","is-referenced-by-count":1,"title":["A data-adaptive methods in detecting exogenous methyltransferase accessible chromatin in human genome using nanopore sequencing"],"prefix":"10.1093","volume":"40","author":[{"given":"Kailing","family":"Tu","sequence":"first","affiliation":[{"name":"National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, Sichuan 610000, China"}]},{"given":"Xuemei","family":"Li","sequence":"additional","affiliation":[{"name":"National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, Sichuan 610000, China"}]},{"given":"Qilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, Sichuan 610000, China"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, Key Laboratory for Applied Statistics of the Ministry of Education, Northeast Normal University , Changchun 130024, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-5541","authenticated-orcid":false,"given":"Dan","family":"Xie","sequence":"additional","affiliation":[{"name":"National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, Sichuan 610000, China"}]}],"member":"286","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"2024071814074558400_btae206-B1","doi-asserted-by":"crossref","first-page":"e59404","DOI":"10.7554\/eLife.59404","article-title":"Massively multiplex single-molecule oligonucleosome footprinting","volume":"9","author":"Abdulhay","year":"2020","journal-title":"Elife"},{"key":"2024071814074558400_btae206-B2","article-title":"Profiling chromatin accessibility in humans using adenine methylation and long-read sequencing","author":"Akbari","year":"2023","journal-title":"bioRxiv"},{"key":"2024071814074558400_btae206-B3","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/s41588-022-01188-8","article-title":"Long-range phasing of dynamic, tissue-specific and allele-specific regulatory elements","volume":"54","author":"Battaglia","year":"2022","journal-title":"Nat Genet"},{"key":"2024071814074558400_btae206-B4","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nmeth.2688","article-title":"Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position","volume":"10","author":"Buenrostro","year":"2013","journal-title":"Nat Methods"},{"key":"2024071814074558400_btae206-B5","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s13577-020-00353-7","article-title":"RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma","volume":"33","author":"Chen","year":"2020","journal-title":"Hum Cell"},{"key":"2024071814074558400_btae206-B6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"Consortium, E.P","year":"2012","journal-title":"Nature"},{"key":"2024071814074558400_btae206-B7","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nmeth888","article-title":"DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays","volume":"3","author":"Crawford","year":"2006","journal-title":"Nat Methods"},{"volume-title":"Large-Scale Inference: Empirical Bayes Methods for Estimation, Testing, and Prediction","year":"2012","author":"Efron","key":"2024071814074558400_btae206-B8"},{"key":"2024071814074558400_btae206-B9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13100-016-0065-9","article-title":"Roles for retrotransposon insertions in human disease","volume":"7","author":"Hancks","year":"2016","journal-title":"Mob DNA"},{"key":"2024071814074558400_btae206-B10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41422-022-00730-x","article-title":"scNanoATAC-seq: a long-read single-cell ATAC sequencing method to detect chromatin accessibility and genetic variants simultaneously within an individual cell","volume":"33","author":"Hu","year":"2023","journal-title":"Cell Res"},{"key":"2024071814074558400_btae206-B11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nbt.4060","article-title":"Nanopore sequencing and assembly of a human genome with ultra-long reads","volume":"36","author":"Jain","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2024071814074558400_btae206-B12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13059-017-1150-1","article-title":"Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania","volume":"18","author":"Kawasaki","year":"2017","journal-title":"Genome Biol"},{"key":"2024071814074558400_btae206-B13","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1101\/gr.143008.112","article-title":"Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules","volume":"22","author":"Kelly","year":"2012","journal-title":"Genome Res"},{"key":"2024071814074558400_btae206-B14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41576-018-0089-8","article-title":"Chromatin accessibility and the regulatory epigenome","volume":"20","author":"Klemm","year":"2019","journal-title":"Nat Rev Genet"},{"key":"2024071814074558400_btae206-B15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13059-019-1910-1","article-title":"Transcriptome assembly from long-read RNA-seq alignments with StringTie2","volume":"20","author":"Kovaka","year":"2019","journal-title":"Genome Biol"},{"key":"2024071814074558400_btae206-B16","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/s41592-020-01000-7","article-title":"Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing","volume":"17","author":"Lee","year":"2020","journal-title":"Nat Methods"},{"key":"2024071814074558400_btae206-B17","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"2024071814074558400_btae206-B18","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1093\/bioinformatics\/btab705","article-title":"New strategies to improve minimap2 alignment accuracy","volume":"37","author":"Li","year":"2021","journal-title":"Bioinformatics"},{"key":"2024071814074558400_btae206-B19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12935-018-0713-x","article-title":"An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma","volume":"18","author":"Li","year":"2018","journal-title":"Cancer Cell Int"},{"key":"2024071814074558400_btae206-B20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-1-0716-2140-0_15","article-title":"Single-molecule multikilobase-scale profiling of chromatin accessibility using m6A-SMAC-Seq and m6A-CpG-GpC-SMAC-Seq","volume":"2458","author":"Marinov","year":"2022","journal-title":"Methods Mol Biol"},{"key":"2024071814074558400_btae206-B21","doi-asserted-by":"crossref","first-page":"11485","DOI":"10.1038\/ncomms11485","article-title":"MNase titration reveals differences between nucleosome occupancy and chromatin accessibility","volume":"7","author":"Mieczkowski","year":"2016","journal-title":"Nat Commun"},{"volume-title":"Machine Learning: A Probabilistic Perspective","year":"2012","author":"Murphy","key":"2024071814074558400_btae206-B22"},{"key":"2024071814074558400_btae206-B23","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1158\/1078-0432.CCR-16-2909","article-title":"Overexpression of RCC2 enhances cell motility and promotes tumor metastasis in lung adenocarcinoma by inducing Epithelial-Mesenchymal transition","volume":"23","author":"Pang","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2024071814074558400_btae206-B24","doi-asserted-by":"crossref","first-page":"ISCB Comm J-304","DOI":"10.12688\/f1000research.23297.1","article-title":"GFF utilities: GffRead and GffCompare","volume":"9","author":"Pertea","year":"2020","journal-title":"F1000Res"},{"key":"2024071814074558400_btae206-B25","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nmeth890","article-title":"Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays","volume":"3","author":"Sabo","year":"2006","journal-title":"Nat Methods"},{"key":"2024071814074558400_btae206-B26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41592-019-0730-2","article-title":"Long-range single-molecule mapping of chromatin accessibility in eukaryotes","volume":"17","author":"Shipony","year":"2020","journal-title":"Nat Methods"},{"key":"2024071814074558400_btae206-B27","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1126\/science.aaz1646","article-title":"Single-molecule regulatory architectures captured by chromatin fiber sequencing","volume":"368","author":"Stergachis","year":"2020","journal-title":"Science"},{"key":"2024071814074558400_btae206-B28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0378-1119(94)00783-O","article-title":"Sequence motifs characteristic for DNA [cytosine-N4] and DNA [adenine-N6] methyltransferases. Classification of all DNA methyltransferases","volume":"157","author":"Timinskas","year":"1995","journal-title":"Gene"},{"year":"2022","author":"Tu","key":"2024071814074558400_btae206-B29"},{"key":"2024071814074558400_btae206-B30","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1101\/gr.251116.119","article-title":"Single-molecule long-read sequencing reveals the chromatin basis of gene expression","volume":"29","author":"Wang","year":"2019","journal-title":"Genome Res"},{"key":"2024071814074558400_btae206-B31","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41388-021-02099-4","article-title":"BRD4 drives esophageal squamous cell carcinoma growth by promoting RCC2 expression","volume":"41","author":"Wu","year":"2022","journal-title":"Oncogene"},{"key":"2024071814074558400_btae206-B32","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.cell.2018.10.006","article-title":"N(6)-methyladenine DNA modification in glioblastoma","volume":"175","author":"Xie","year":"2018","journal-title":"Cell"},{"key":"2024071814074558400_btae206-B33","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1101\/gr.249789.119","article-title":"Genome-wide analysis of polymerase III-transcribed Alu elements suggests cell-type-specific enhancer function","volume":"29","author":"Zhang","year":"2019","journal-title":"Genome Res"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae206\/57230260\/btae206.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/5\/btae206\/58585437\/btae206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/5\/btae206\/58585437\/btae206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T15:35:00Z","timestamp":1721316900000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae206\/7645405"}},"subtitle":[],"editor":[{"given":"Alfonso","family":"Valencia","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae206","relation":{},"ISSN":["1367-4811"],"issn-type":[{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2024,5,1]]},"published":{"date-parts":[[2024,4,13]]},"article-number":"btae206"}}