{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:21:37Z","timestamp":1757622097350,"version":"3.44.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Cellular development and differentiation in Eukaryotes depends upon sequential gene regulatory decisions that allow a single genome to encode many hundreds of distinct cellular phenotypes. Decisions are stored in the regulatory state of each cell, an important part of which is the epi-genome\u2014the collection of proteins, RNA and their specific associations with the genome. Additionally, further cellular responses are, in part, determined by this regulatory state. To date, models of regulatory state have failed to include the contingency of incoming regulatory signals on the current epi-genetic state and none have done so at the whole-genome level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here we introduce GenomicLayers, a new R package to run rules-based simulations of epigenetic state changes genome-wide in Eukaryotes. Simulations model the accumulation of changes to genome-wide <jats:italic>layers<\/jats:italic> by user-specified <jats:italic>binding factors<\/jats:italic>. As a first exemplar, we show two versions of a simple model of the recruitment and spreading of epigenetic marks near telomeres in the yeast <jats:italic>Saccharomyces cerevisiae<\/jats:italic>. By combining the output from 100 runs of the simulation, we generate whole genome predictions of epigenetic state at 1\u00a0bp resolution. The example yeast models are included within a \u2018vignette\u2019 with the GenomicLayers package, which is available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/github.com\/davetgerrard\/GenomicLayers\" ext-link-type=\"uri\">https:\/\/github.com\/davetgerrard\/GenomicLayers<\/jats:ext-link>. To demonstrate the use of GenomicLayers on the full human reference genome (hg38), we show the results from parameter refinement on a simplistic model of the action of pluripotency factors against a self-spreading repressor seeded at CpG islands. The human genome model is included in supplementary information as an R script.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>GenomicLayers enables scientists working on diverse eukaryotic organisms to test models of gene regulation in silico. Applications include epigenetic silencing, activation by combinatorial binding of transcription factors and the sink effects caused by down-regulation of components of epigenetic regulators. The software is intended to be used to parameterise, refine and combine models and thereby capitalise on data from the thousands of studies of Eukaryotic epigenomes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12859-025-06224-y","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T18:38:44Z","timestamp":1754332724000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GenomicLayers: sequence-based simulation of epi-genomes"],"prefix":"10.1186","volume":"26","author":[{"given":"Dave T.","family":"Gerrard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"issue":"11","key":"6224_CR1","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nrg.2017.57","volume":"18","author":"Y Atlasi","year":"2017","unstructured":"Atlasi Y, Stunnenberg HG. The interplay of epigenetic marks during stem cell differentiation and development. Nat Rev Genet. 2017;18(11):643\u201358. https:\/\/doi.org\/10.1038\/nrg.2017.57.","journal-title":"Nat Rev Genet"},{"key":"6224_CR2","doi-asserted-by":"publisher","first-page":"e41017","DOI":"10.7554\/eLife.41017","volume":"8","author":"JW Biddle","year":"2019","unstructured":"Biddle JW, Nguyen M, Gunawardena J. Negative reciprocity, not ordered assembly, underlies the interaction of Sox2 and Oct4 on DNA. Edited by Naama Barkai. Elife. 2019;8:e41017. https:\/\/doi.org\/10.7554\/eLife.41017.","journal-title":"Elife"},{"issue":"10","key":"6224_CR3","doi-asserted-by":"publisher","first-page":"2808","DOI":"10.1093\/molbev\/msaa082","volume":"37","author":"EJ Brown","year":"2020","unstructured":"Brown EJ, Nguyen AH, Bachtrog D. The Drosophila Y chromosome affects heterochromatin integrity genome-wide. Mol Biol Evol. 2020;37(10):2808\u201324. https:\/\/doi.org\/10.1093\/molbev\/msaa082.","journal-title":"Mol Biol Evol"},{"issue":"6","key":"6224_CR4","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/j.cell.2014.01.062","volume":"156","author":"J Chen","year":"2014","unstructured":"Chen J, Zhang Z, Li Li, Chen B-C, Revyakin A, Hajj B, Legant W, et al. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell. 2014;156(6):1274\u201385. https:\/\/doi.org\/10.1016\/j.cell.2014.01.062.","journal-title":"Cell"},{"issue":"12","key":"6224_CR5","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1080\/15592294.2017.1403693","volume":"12","author":"N Chung","year":"2017","unstructured":"Chung N, Bogliotti YS, Ding W, Vilarino M, Takahashi K, Chitwood JL, Schultz RM, Ross PJ. Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos. Epigenetics. 2017;12(12):1048\u201356. https:\/\/doi.org\/10.1080\/15592294.2017.1403693.","journal-title":"Epigenetics"},{"key":"6224_CR6","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/B978-0-12-803075-2.00007-6","volume-title":"Epigenetics and systems biology","author":"IB Dodd","year":"2017","unstructured":"Dodd IB, Sneppen K. Chapter 7\u2014modeling bistable chromatin states. In: Ringrose L, editor. Epigenetics and systems biology. Boston: Academic Press; 2017. p. 145\u201368."},{"issue":"8","key":"6224_CR7","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/nprot.2009.97","volume":"4","author":"S Durinck","year":"2009","unstructured":"Durinck S, Spellman PT, Birney E, Huber W. Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt. Nat Protoc. 2009;4(8):1184\u201391. https:\/\/doi.org\/10.1038\/nprot.2009.97.","journal-title":"Nat Protoc"},{"issue":"1","key":"6224_CR8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ajhg.2017.11.013","volume":"102","author":"V Faundes","year":"2018","unstructured":"Faundes V, Newman WG, Bernardini L, Canham N, Clayton-Smith J, Dallapiccola B, Davies SJ, et al. Histone lysine methylases and demethylases in the landscape of human developmental disorders. Am J Hum Genet. 2018;102(1):175\u201387. https:\/\/doi.org\/10.1016\/j.ajhg.2017.11.013.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"6224_CR9","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s41467-022-28434-1","volume":"13","author":"M Gao","year":"2022","unstructured":"Gao M, Veil M, Rosenblatt M, Riesle AJ, Gebhard A, Hass H, Buryanova L, et al. Pluripotency factors determine gene expression repertoire at zygotic genome activation. Nat Commun. 2022;13(1):788. https:\/\/doi.org\/10.1038\/s41467-022-28434-1.","journal-title":"Nat Commun"},{"issue":"1","key":"6224_CR10","doi-asserted-by":"publisher","first-page":"3920","DOI":"10.1038\/s41467-020-17305-2","volume":"11","author":"DT Gerrard","year":"2020","unstructured":"Gerrard DT, Berry AA, Jennings RE, Birket MJ, Zarrineh P, Garstang MG, Withey SL, et al. Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders. Nat Commun. 2020;11(1):3920. https:\/\/doi.org\/10.1038\/s41467-020-17305-2.","journal-title":"Nat Commun"},{"issue":"14","key":"6224_CR11","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200547","volume":"149","author":"DW Hagey","year":"2022","unstructured":"Hagey DW, Bergsland M, Muhr J. SOX2 transcription factor binding and function. Development. 2022;149(14): dev200547. https:\/\/doi.org\/10.1242\/dev.200547.","journal-title":"Development"},{"issue":"14","key":"6224_CR12","doi-asserted-by":"publisher","first-page":"6162","DOI":"10.1073\/pnas.88.14.6162","volume":"88","author":"TD Halazonetis","year":"1991","unstructured":"Halazonetis TD, Kandil AN. Determination of the C-MYC DNA-binding site. Proc Natl Acad Sci U S A. 1991;88(14):6162\u20136. https:\/\/doi.org\/10.1073\/pnas.88.14.6162.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"6224_CR13","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev-arplant-042110-103806","volume":"62","author":"G He","year":"2011","unstructured":"He G, Elling AA, Deng XW. The epigenome and plant development. Annu Rev Plant Biol. 2011;62(1):411\u201335. https:\/\/doi.org\/10.1146\/annurev-arplant-042110-103806.","journal-title":"Annu Rev Plant Biol"},{"issue":"3","key":"6224_CR14","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.bbagrm.2013.10.001","volume":"1839","author":"S Jerabek","year":"2014","unstructured":"Jerabek S, Merino F, Sch\u00f6ler HR, Cojocaru V. OCT4: dynamic DNA binding pioneers stem cell pluripotency. Biochim Biophys Acta Gene Regul Mech. 2014;1839(3):138\u201354. https:\/\/doi.org\/10.1016\/j.bbagrm.2013.10.001.","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"issue":"3","key":"6224_CR15","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/ng993","volume":"32","author":"A Kimura","year":"2002","unstructured":"Kimura A, Umehara T, Horikoshi M. Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Nat Genet. 2002;32(3):370\u20137. https:\/\/doi.org\/10.1038\/ng993.","journal-title":"Nat Genet"},{"issue":"2","key":"6224_CR16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0968-0004(97)01008-6","volume":"22","author":"P K\u00f6nig","year":"1997","unstructured":"K\u00f6nig P, Rhodes D. Recognition of telomeric DNA. Trends Biochem Sci. 1997;22(2):43\u20137. https:\/\/doi.org\/10.1016\/S0968-0004(97)01008-6.","journal-title":"Trends Biochem Sci"},{"issue":"7","key":"6224_CR17","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1093\/bioinformatics\/btac057","volume":"38","author":"NE Kramer","year":"2022","unstructured":"Kramer NE, Davis ES, Wenger CD, Deoudes EM, Parker SM, Love MI, Phanstiel DH. Plotgardener: cultivating precise multi-panel figures in R. Bioinformatics. 2022;38(7):2042\u20135. https:\/\/doi.org\/10.1093\/bioinformatics\/btac057.","journal-title":"Bioinformatics"},{"issue":"8","key":"6224_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003118","volume":"9","author":"M Lawrence","year":"2013","unstructured":"Lawrence M, Huber W, Pag\u00e8s H, Aboyoun P, Carlson M, Gentleman R, Morgan MT, Carey VJ. Software for computing and annotating genomic ranges. PLoS Comput Biol. 2013;9(8): e1003118. https:\/\/doi.org\/10.1371\/journal.pcbi.1003118.","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"6224_CR19","doi-asserted-by":"publisher","first-page":"4859","DOI":"10.1093\/nar\/gku134","volume":"42","author":"Y Liu","year":"2014","unstructured":"Liu Y, Olanrewaju YO, Zheng Yu, Hashimoto H, Blumenthal RM, Zhang X, Cheng X. Structural basis for Klf4 recognition of methylated DNA. Nucleic Acids Res. 2014;42(8):4859\u201367. https:\/\/doi.org\/10.1093\/nar\/gku134.","journal-title":"Nucleic Acids Res"},{"issue":"4980","key":"6224_CR20","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1126\/science.2237406","volume":"250","author":"AJ Lustig","year":"1990","unstructured":"Lustig AJ, Kurtz S, Shore D. Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science. 1990;250(4980):549\u201353. https:\/\/doi.org\/10.1126\/science.2237406.","journal-title":"Science"},{"issue":"1","key":"6224_CR21","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4161\/epi.7.1.18750","volume":"7","author":"K Martins-Taylor","year":"2012","unstructured":"Martins-Taylor K, Schroeder DI, LaSalle JM, Lalande M, Xu R-H. Role of DNMT3B in the regulation of early neural and neural crest specifiers. Epigenetics. 2012;7(1):71\u201382. https:\/\/doi.org\/10.4161\/epi.7.1.18750.","journal-title":"Epigenetics"},{"issue":"16","key":"6224_CR22","doi-asserted-by":"publisher","first-page":"3166","DOI":"10.1128\/MCB.00364-13","volume":"33","author":"DM Meredith","year":"2013","unstructured":"Meredith DM, Borromeo MD, Deering TG, Casey BH, Savage TK, Mayer PR, Hoang C, et al. Program specificity for Ptf1a in pancreas versus neural tube development correlates with distinct collaborating cofactors and chromatin accessibility. Mol Cell Biol. 2013;33(16):3166\u201379. https:\/\/doi.org\/10.1128\/MCB.00364-13.","journal-title":"Mol Cell Biol"},{"issue":"5","key":"6224_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000478","volume":"5","author":"A Miele","year":"2009","unstructured":"Miele A, Bystricky K, Dekker J. Yeast silent mating type loci form heterochromatic clusters through silencer protein-dependent long-range interactions. PLoS Genet. 2009;5(5): e1000478. https:\/\/doi.org\/10.1371\/journal.pgen.1000478.","journal-title":"PLoS Genet"},{"issue":"7905","key":"6224_CR24","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41586-022-04558-8","volume":"604","author":"J Morales","year":"2022","unstructured":"Morales J, Pujar S, Loveland JE, Astashyn A, Bennett R, Berry A, Cox E, et al. A joint NCBI and EMBL-EBI transcript set for clinical genomics and research. Nature. 2022;604(7905):310\u20135. https:\/\/doi.org\/10.1038\/s41586-022-04558-8.","journal-title":"Nature"},{"issue":"15","key":"6224_CR25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022887118","volume":"118","author":"JF Nickels","year":"2021","unstructured":"Nickels JF, Edwards AK, Charlton SJ, Mortensen AM, Hougaard SCL, Trusina A, Sneppen K, Thon G. Establishment of heterochromatin in domain-size-dependent bursts. Proc Natl Acad Sci U S A. 2021;118(15): e2022887118. https:\/\/doi.org\/10.1073\/pnas.2022887118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6224_CR26","unstructured":"Pag\u00e8s H. BSgenome: software Infrastructure for Efficient Representation of Full Genomes and Their SNPs. 2024. https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/BSgenome.html."},{"issue":"10","key":"6224_CR27","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/nbt.1685","volume":"28","author":"A Portela","year":"2010","unstructured":"Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057\u201368. https:\/\/doi.org\/10.1038\/nbt.1685.","journal-title":"Nat Biotechnol"},{"key":"6224_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-3-r25","volume":"14","author":"JP Reddington","year":"2013","unstructured":"Reddington JP, Perricone SM, Nestor CE, Reichmann J, Youngson NA, Suzuki M, Reinhardt D, et al. Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes. Genome Biol. 2013;14: R25. https:\/\/doi.org\/10.1186\/gb-2013-14-3-r25.","journal-title":"Genome Biol"},{"issue":"7539","key":"6224_CR29","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","volume":"518","author":"A Kundaje","year":"2015","unstructured":"Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518(7539):317\u201330. https:\/\/doi.org\/10.1038\/nature14248.","journal-title":"Nature"},{"key":"6224_CR30","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1146\/annurev.biochem.72.121801.161547","volume":"72","author":"LN Rusche","year":"2003","unstructured":"Rusche LN, Kirchmaier AL, Rine J. The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem. 2003;72:481\u2013516. https:\/\/doi.org\/10.1146\/annurev.biochem.72.121801.161547.","journal-title":"Annu Rev Biochem"},{"issue":"3","key":"6224_CR31","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/ng1017","volume":"32","author":"N Suka","year":"2002","unstructured":"Suka N, Luo K, Grunstein M. Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nat Genet. 2002;32(3):378\u201383. https:\/\/doi.org\/10.1038\/ng1017.","journal-title":"Nat Genet"},{"issue":"3","key":"6224_CR32","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/nrm.2016.8","volume":"17","author":"K Takahashi","year":"2016","unstructured":"Takahashi K, Yamanaka S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat Rev Mol Cell Biol. 2016;17(3):183\u201393. https:\/\/doi.org\/10.1038\/nrm.2016.8.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"6","key":"6224_CR33","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.stemcr.2015.04.009","volume":"4","author":"Y Tanaka","year":"2015","unstructured":"Tanaka Y, Hysolli E, Su J, Xiang Y, Kim K-Y, Zhong M, Li Y, et al. Transcriptome signature and regulation in human somatic cell reprogramming. Stem Cell Reports. 2015;4(6):1125\u201339. https:\/\/doi.org\/10.1016\/j.stemcr.2015.04.009","journal-title":"Stem Cell Reports"},{"key":"6224_CR34","doi-asserted-by":"publisher","DOI":"10.5936\/csbj.201304001","volume":"7","author":"S-Y Tung","year":"2013","unstructured":"Tung S-Y, Lee K-W, Hong J-Y, Lee S-P, Shen H-H, Liou G-G. Changes in the genome-wide localization pattern of Sir3 in Saccharomyces cerevisiae during different growth stages. Comput Struct Biotechnol J. 2013;7(June): e201304001. https:\/\/doi.org\/10.5936\/csbj.201304001.","journal-title":"Comput Struct Biotechnol J"},{"issue":"12","key":"6224_CR35","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1093\/nar\/28.12.2292","volume":"28","author":"J Wahlin","year":"2000","unstructured":"Wahlin J, Cohn M. Saccharomyces cerevisiae RAP1 binds to telomeric sequences with spatial flexibility. Nucleic Acids Res. 2000;28(12):2292\u2013301. https:\/\/doi.org\/10.1093\/nar\/28.12.2292","journal-title":"Nucleic Acids Res"},{"issue":"24","key":"6224_CR36","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.1007\/s00018-014-1725-x","volume":"71","author":"J Wang","year":"2014","unstructured":"Wang J, Lawry ST, Cohen AL, Jia S. Chromosome boundary elements and regulation of heterochromatin spreading. Cell Mol Life Sci CMLS. 2014;71(24):4841\u201352. https:\/\/doi.org\/10.1007\/s00018-014-1725-x","journal-title":"Cell Mol Life Sci CMLS"},{"key":"6224_CR37","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.pbi.2016.08.002","volume":"34","author":"J Xiao","year":"2016","unstructured":"Xiao J, Lee US, Wagner D. Tug of war: adding and removing histone lysine methylation in Arabidopsis. Curr Opin Plant Biol. 2016;34:41\u201353. https:\/\/doi.org\/10.1016\/j.pbi.2016.08.002.","journal-title":"Curr Opin Plant Biol"},{"issue":"6347","key":"6224_CR38","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1126\/science.aam5339","volume":"357","author":"F Zenk","year":"2017","unstructured":"Zenk F, Loeser E, Schiavo R, Kilpert F, Bogdanovi\u0107 O, Iovino N. Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science. 2017;357(6347):212\u20136. https:\/\/doi.org\/10.1126\/science.aam5339.","journal-title":"Science"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-025-06224-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-025-06224-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-025-06224-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T16:52:41Z","timestamp":1757350361000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-025-06224-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,4]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6224"],"URL":"https:\/\/doi.org\/10.1186\/s12859-025-06224-y","relation":{},"ISSN":["1471-2105"],"issn-type":[{"type":"electronic","value":"1471-2105"}],"subject":[],"published":{"date-parts":[[2025,8,4]]},"assertion":[{"value":"9 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"205"}}