{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T08:06:12Z","timestamp":1772697972397,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for Public Universities in Liaoning","award":["LJ242410140009"],"award-info":[{"award-number":["LJ242410140009"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62002056"],"award-info":[{"award-number":["62002056"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liaoning Provincial Science and Technology Plan Joint Program Project","award":["2025-MSLH-306"],"award-info":[{"award-number":["2025-MSLH-306"]}]},{"name":"Liaoning Provincial Science and Technology Plan Joint Program Project","award":["2025-MSLH-323"],"award-info":[{"award-number":["2025-MSLH-323"]}]},{"name":"Liaoning Provincial Science and Technology Plan Joint Program Project","award":["2025-MSLH-112"],"award-info":[{"award-number":["2025-MSLH-112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>N6-methyladenine (6\u2009mA) is an important epigenetic modification of DNA that regulates biological processes such as gene expression, transcription, replication, DNA repair, and cell cycle without altering the DNA sequence. It also plays a key role in many diseases including cancer and autoimmune diseases. Although experimental approaches such as SMRT sequencing and methylated DNA immunoprecipitation can identify 6\u2009mA sites, they suffer from drawbacks including suboptimal sequencing quality, low signal-to-noise ratios, high costs, and time-consuming procedures. In recent years, deep learning approaches have demonstrated significant advantages in predicting 6\u2009mA sites; however, their generalization ability still requires further improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inspired by the state space model Mamba, we propose a novel model for 6\u2009mA site prediction, named Mamba6mA. In the Mamba6mA model, we design position-specific linear layers to replace traditional convolutional layers to facilitate capture specific positional information. Meanwhile, we construct a multi-scale feature extraction module and integrate features captured by sliding windows of different scales, feeding them into the classifier for prediction. Experimental results show that Mamba6mA achieves the best MCC on 9 out of 11 species datasets, surpassing existing state-of-the-art models. Ablation studies confirm that the position-specific linear layers and the multi-scale fusion module contribute MCC performance gains of 2.36% and 2.31%, respectively. Feature visualization analysis further reveals that the model effectively captures sequence patterns upstream and downstream of 6\u2009mA sites providing a new technical approach for studying epigenetic modification mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code for Mamba6mA is available at: https:\/\/linproxy.fan.workers.dev:443\/https\/github.com\/XploreAI-Lab\/Mamba6mA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag060","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:44:43Z","timestamp":1769777083000},"source":"Crossref","is-referenced-by-count":0,"title":["Mamba6mA: a Mamba-based DNA N6-methyladenine site prediction model"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/linproxy.fan.workers.dev:443\/https\/orcid.org\/0000-0002-7981-9478","authenticated-orcid":false,"given":"Qi","family":"Zhao","sequence":"first","affiliation":[{"name":"Liaoning University Faculty of Information, , Shenyang, Liaoning, 110036,","place":["China"]},{"name":"Northeastern University College of Medicine and Biological Information Engineering, , Shenyang, Liaoning, 110000,","place":["China"]}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Northeastern University College of Medicine and Biological Information Engineering, , Shenyang, Liaoning, 110000,","place":["China"]}]},{"given":"Tingwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Liaoning University Faculty of Information, , Shenyang, Liaoning, 110036,","place":["China"]}]},{"given":"Qian","family":"Mao","sequence":"additional","affiliation":[{"name":"Liaoning University College of Light Industry, , Shenyang, Liaoning, 110036,","place":["China"]}]},{"given":"Haoxuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Northeastern University College of Medicine and Biological Information Engineering, , Shenyang, Liaoning, 110000,","place":["China"]}]},{"given":"Jingjing","family":"Chen","sequence":"additional","affiliation":[{"name":"Northeastern University College of Medicine and Biological Information Engineering, , Shenyang, Liaoning, 110000,","place":["China"]}]},{"given":"Zheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Dalian Maritime University College of Artificial Intelligence, , Dalian, Liaoning, 116026,","place":["China"]}]},{"ORCID":"https:\/\/linproxy.fan.workers.dev:443\/https\/orcid.org\/0000-0002-5002-6968","authenticated-orcid":false,"given":"Xiaoya","family":"Fan","sequence":"additional","affiliation":[{"name":"Dalian University of Technology School of Software, , Dalian, Liaoning, 116024,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"2026030502114372400_btag060-B1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.2174\/0929867328666210917115733","article-title":"Research progress in predicting DNA methylation modifications and the relation with human diseases","volume":"29","author":"Ao","year":"2022","journal-title":"Curr Med Chem"},{"key":"2026030502114372400_btag060-B2","doi-asserted-by":"crossref","first-page":"102217","DOI":"10.1016\/j.inffus.2023.102217","article-title":"A survey of multimodal hybrid deep learning for computer vision: architectures, applications, trends, and challenges","volume":"105","author":"Bayoudh","year":"2024","journal-title":"Inf Fusion"},{"key":"2026030502114372400_btag060-B3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(90)90271-F","article-title":"E. coli oriC and the dnaA gene promoter are sequestered from dam methyltransferase following the passage of the chromosomal replication fork","volume":"62","author":"Campbell","year":"1990","journal-title":"Cell"},{"key":"2026030502114372400_btag060-B4","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1093\/bioinformatics\/btz015","article-title":"i6ma-pred: identifying dna n6-methyladenine sites in the rice genome","volume":"35","author":"Chen","year":"2019","journal-title":"Bioinformatics"},{"key":"2026030502114372400_btag060-B5","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nmeth.1459","article-title":"Direct detection of dna methylation during single-molecule, real-time sequencing","volume":"7","author":"Flusberg","year":"2010","journal-title":"Nat Methods"},{"key":"2026030502114372400_btag060-B6","author":"Gao","year":"2024"},{"key":"2026030502114372400_btag060-B7","author":"Gu","year":"2023"},{"key":"2026030502114372400_btag060-B8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3390\/biom10010062","article-title":"Epigenetics analysis and integrated analysis of multiomics data, including epigenetic data, using artificial intelligence in the era of precision medicine","volume":"10","author":"Hamamoto","year":"2019","journal-title":"Biomolecules"},{"key":"2026030502114372400_btag060-B9","author":"Kingma","year":"2014"},{"key":"2026030502114372400_btag060-B10","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3390\/genes10100828","article-title":"i6ma-dncp: computational identification of dna n 6-methyladenine sites in the rice genome using optimized dinucleotide-based features","volume":"10","author":"Kong","year":"2019","journal-title":"Genes (Basel)"},{"key":"2026030502114372400_btag060-B11","doi-asserted-by":"crossref","first-page":"e1008767","DOI":"10.1371\/journal.pcbi.1008767","article-title":"Deep6ma: a deep learning framework for exploring similar patterns in dna n6-methyladenine sites across different species","volume":"17","author":"Li","year":"2021","journal-title":"PLoS Comput Biol"},{"key":"2026030502114372400_btag060-B12","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1038\/s41467-019-10168-2","article-title":"Detection of dna base modifications by deep recurrent neural network on oxford nanopore sequencing data","volume":"10","author":"Liu","year":"2019","journal-title":"Nat Commun"},{"key":"2026030502114372400_btag060-B13","doi-asserted-by":"crossref","first-page":"bbaa124","DOI":"10.1093\/bib\/bbaa124","article-title":"Deeptorrent: a deep learning-based approach for predicting dna n4-methylcytosine sites","volume":"22","author":"Liu","year":"2021","journal-title":"Brief Bioinform"},{"key":"2026030502114372400_btag060-B14","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41586-022-05580-6","article-title":"A dna methylation atlas of normal human cell types","volume":"613","author":"Loyfer","year":"2023","journal-title":"Nature"},{"key":"2026030502114372400_btag060-B15","doi-asserted-by":"crossref","first-page":"100991","DOI":"10.1016\/j.isci.2020.100991","article-title":"idna-ms: an integrated computational tool for detecting dna modification sites in multiple genomes","volume":"23","author":"Lv","year":"2020","journal-title":"iScience"},{"key":"2026030502114372400_btag060-B16","author":"McInnes","year":"2018"},{"key":"2026030502114372400_btag060-B17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-59745-522-0_5","article-title":"Methylated dna immunoprecipitation (medip)","volume":"507","author":"Mohn","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2026030502114372400_btag060-B18","first-page":"1212","article-title":"plogo: a probabilistic approach to visualizing sequence motifs","volume":"10","author":"O\u2019shea","year":"2013","journal-title":"Nat Methods"},{"key":"2026030502114372400_btag060-B19","author":"Paszke","year":"2017"},{"key":"2026030502114372400_btag060-B20","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/genetics\/104.4.571","article-title":"Effects of high levels of dna adenine methylation on methyl-directed mismatch repair in Escherichia coli","volume":"104","author":"Pukkila","year":"1983","journal-title":"Genetics"},{"key":"2026030502114372400_btag060-B21","doi-asserted-by":"crossref","first-page":"7027","DOI":"10.1128\/JB.187.20.7027-7037.2005","article-title":"Analysis of global gene expression and double-strand-break formation in dna adenine methyltransferase-and mismatch repair-deficient Escherichia coli","volume":"187","author":"Robbins-Manke","year":"2005","journal-title":"J Bacteriol"},{"key":"2026030502114372400_btag060-B22","doi-asserted-by":"crossref","first-page":"101821","DOI":"10.1016\/j.tranon.2023.101821","article-title":"Epigenetic modifications: key players in cancer heterogeneity and drug resistance","volume":"39","author":"Sadida","year":"2024","journal-title":"Transl Oncol"},{"key":"2026030502114372400_btag060-B23","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.3390\/ijms25063098","article-title":"An overview of current detection methods for rna methylation","volume":"25","author":"Saglam","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026030502114372400_btag060-B24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/ac0489420","article-title":"Specific method for the determination of genomic dna methylation by liquid chromatography-electrospray ionization tandem mass spectrometry","volume":"77","author":"Song","year":"2005","journal-title":"Anal Chem"},{"key":"2026030502114372400_btag060-B25","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/bioinformatics\/btx622","article-title":"Tumor origin detection with tissue-specific mirna and dna methylation markers","volume":"34","author":"Tang","year":"2018","journal-title":"Bioinformatics"},{"key":"2026030502114372400_btag060-B26","doi-asserted-by":"crossref","first-page":"bbac053","DOI":"10.1093\/bib\/bbac053","article-title":"Bert6ma: prediction of dna n6-methyladenine site using deep learning-based approaches","volume":"23","author":"Tsukiyama","year":"2022","journal-title":"Brief Bioinform"},{"key":"2026030502114372400_btag060-B27","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.csbj.2022.12.043","article-title":"Cnn6ma: interpretable neural network model based on position-specific cnn and cross-interactive network for 6ma site prediction","volume":"21","author":"Tsukiyama","year":"2023","journal-title":"Comput Struct Biotechnol J"},{"key":"2026030502114372400_btag060-B28","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.molcel.2018.06.015","article-title":"N6-methyladenine dna modification in the human genome","volume":"71","author":"Xiao","year":"2018","journal-title":"Mol Cell"},{"key":"2026030502114372400_btag060-B29","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.3389\/fgene.2019.01071","article-title":"Snnrice6ma: a deep learning method for predicting dna n6-methyladenine sites in rice genome","volume":"10","author":"Yu","year":"2019","journal-title":"Front Genet"},{"key":"2026030502114372400_btag060-B30","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1093\/bioinformatics\/btab677","article-title":"idna-abt: advanced deep learning model for detecting dna methylation with adaptive features and transductive information maximization","volume":"37","author":"Yu","year":"2021","journal-title":"Bioinformatics"},{"key":"2026030502114372400_btag060-B31","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1162\/neco_a_01199","article-title":"A review of recurrent neural networks: Lstm cells and network architectures","volume":"31","author":"Yu","year":"2019","journal-title":"Neural Comput"},{"key":"2026030502114372400_btag060-B32","first-page":"50","author":"Zhang","year":"2024"},{"key":"2026030502114372400_btag060-B33","doi-asserted-by":"crossref","first-page":"bbaf360","DOI":"10.1093\/bib\/bbaf360","article-title":"Mambacpg: an accurate model for single-cell dna methylation status imputation using mamba","volume":"26","author":"Zhao","year":"2025","journal-title":"Brief Bioinform"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag060\/66792048\/btag060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/academic.oup.com\/bioinformatics\/article-pdf\/42\/3\/btag060\/66792048\/btag060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/academic.oup.com\/bioinformatics\/article-pdf\/42\/3\/btag060\/66792048\/btag060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:11:52Z","timestamp":1772694712000},"score":1,"resource":{"primary":{"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btag060\/8465948"}},"subtitle":[],"editor":[{"given":"Jianlin","family":"Cheng","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2,28]]}},"URL":"https:\/\/linproxy.fan.workers.dev:443\/https\/doi.org\/10.1093\/bioinformatics\/btag060","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,5]]},"article-number":"btag060"}}