{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:19:29Z","timestamp":1787768369531,"version":"build-2784847793"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangxi Provincial Department of Education Science and Technology Research Project","award":["Grant No. GJJ2500812"],"award-info":[{"award-number":["Grant No. GJJ2500812"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Grant No. 32460178, 32100632"],"award-info":[{"award-number":["Grant No. 32460178, 32100632"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["Grant No. 20232BCJ23015, 20232ACB215002"],"award-info":[{"award-number":["Grant No. 20232BCJ23015, 20232ACB215002"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for Academic and Technical Leaders of Jiangxi Province","award":["Grant No.20213BCJ22016"],"award-info":[{"award-number":["Grant No.20213BCJ22016"]}]},{"name":"Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program","award":["Grant No. CXTD22015"],"award-info":[{"award-number":["Grant No. CXTD22015"]}]},{"name":"Jiangxi Province Key Laboratory of Pharmacology of Traditional Chinese Medicine","award":["Grant No. 2024SSY07111"],"award-info":[{"award-number":["Grant No. 2024SSY07111"]}]},{"name":"Jiangxi Provincial Key Laboratory of Hematological Diseases","award":["Grant No. 2024SSY06051"],"award-info":[{"award-number":["Grant No. 2024SSY06051"]}]},{"name":"Beijing Natural Science Foundation","award":["Grant No. J230022, L222125"],"award-info":[{"award-number":["Grant No. J230022, L222125"]}]},{"name":"Doctoral Research Startup Fund of Jiangxi University of Chinese Medicine","award":["Grant No. 5252300323"],"award-info":[{"award-number":["Grant No. 5252300323"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Technical advances in RNA sequencing (RNA-seq) and Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) provide us a genome-wide method to deeper insights into gene expression and regulation. The lack of user-friendly bioinformatics platforms poses a challenge for accurately interpreting such datasets. Here, we present a computational platform, RAGER, that integrates the popular bioinformatics tools in an automated thread for joint mining of RNA-seq and ATAC-seq data. RAGER facilitates integrative analysis of transcriptome and chromatin accessibility by providing an automated workflow that minimizes the need for bioinformatics expertise and significantly reduces processing time. We demonstrate RAGER\u2019s utility for novel biological discovery by characterizing the transcriptome and chromatin accessibility of two recently published datasets. RAGER was implemented using Snakemake and is freely available via\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/bioinfo202408\/RAGER\" xlink:type=\"simple\">https:\/\/github.com\/bioinfo202408\/RAGER<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0349941","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:22:41Z","timestamp":1779470561000},"page":"e0349941","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["RAGER: A user-friendly computational platform for integrated analysis of RNA-Seq and ATAC-seq data"],"prefix":"10.1371","volume":"21","author":[{"given":"Yunjie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1232-1074","authenticated-orcid":true,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"pone.0349941.ref001","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev-anchem-061622-015112","article-title":"The 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Development and Disorders","volume":"131","author":"J Lyu","year":"2024","journal-title":"Exp Hematol"},{"issue":"5","key":"pone.0349941.ref028","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adj9479","article-title":"Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis","volume":"10","author":"AG Maynard","year":"2024","journal-title":"Sci Adv"},{"issue":"2","key":"pone.0349941.ref029","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1182\/blood-2011-04-285981","article-title":"Transcription factor networks in erythroid cell and megakaryocyte development","volume":"118","author":"LC Dor\u00e9","year":"2011","journal-title":"Blood"},{"issue":"4","key":"pone.0349941.ref030","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3892\/etm.2021.10539","article-title":"Downregulation of KLF4 activates embryonic and fetal globin mRNA expression in human erythroid progenitor cells","volume":"22","author":"P Khamphikham","year":"2021","journal-title":"Exp Ther Med"},{"key":"pone.0349941.ref031","doi-asserted-by":"crossref","first-page":"104730","DOI":"10.1016\/j.exphem.2025.104730","article-title":"KLF4 enhances transplantation-induced hematopoiesis by inhibiting TLRs and noncanonical NF\u03baB signaling at a steady state","volume":"144","author":"CS Park","year":"2025","journal-title":"Exp Hematol"},{"key":"pone.0349941.ref032","doi-asserted-by":"crossref","unstructured":"Wei Z, Zhang W, Fang H, Li Y, Wang X. esATAC: an easy-to-use systematic pipeline for ATAC-seq data analysis. https:\/\/doi.org\/10.1093\/bioinformatics\/bty141","DOI":"10.1093\/bioinformatics\/bty141"},{"issue":"15","key":"pone.0349941.ref033","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1093\/bioinformatics\/btu169","article-title":"PRADA: pipeline for RNA sequencing data analysis","volume":"30","author":"W 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