{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:50:42Z","timestamp":1776325842607,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T00:00:00Z","timestamp":1480032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T00:00:00Z","timestamp":1480032000000},"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><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>CpG sites in an individual molecule may exist in a binary state (methylated or unmethylated) and each individual DNA molecule, containing a certain number of CpGs, is a combination of these states defining an epihaplotype. Classic quantification based approaches to study DNA methylation are intrinsically unable to fully represent the complexity of the underlying methylation substrate. Epihaplotype based approaches, on the other hand, allow methylation profiles of cell populations to be studied at the single molecule level.<\/jats:p>\n                <jats:p>For such investigations, next-generation sequencing techniques can be used, both for quantitative and for epihaplotype analysis. Currently available tools for methylation analysis lack output formats that explicitly report CpG methylation profiles at the single molecule level and that have suited statistical tools for their interpretation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here we present ampliMethProfiler, a python-based pipeline for the extraction and statistical epihaplotype analysis of amplicons from targeted deep bisulfite sequencing of multiple DNA regions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>ampliMethProfiler tool provides an easy and user friendly way to extract and analyze the epihaplotype composition of reads from targeted bisulfite sequencing experiments. <jats:italic>ampliMethProfiler<\/jats:italic> is written in python language and requires a local installation of BLAST and (optionally) QIIME tools. It can be run on Linux and OS X platforms. The software is open source and freely available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/amplimethprofiler.sourceforge.net\/\">http:\/\/amplimethprofiler.sourceforge.net<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-016-1380-3","type":"journal-article","created":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T01:06:56Z","timestamp":1480036016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["ampliMethProfiler: a pipeline for the analysis of CpG methylation profiles of targeted deep bisulfite sequenced amplicons"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-9426","authenticated-orcid":false,"given":"Giovanni","family":"Scala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella","family":"Affinito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermanno","family":"Florio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Monticelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennaro","family":"Miele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Chiariotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Cocozza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,25]]},"reference":[{"issue":"10","key":"1380_CR1","doi-asserted-by":"publisher","first-page":"e76953","DOI":"10.1371\/journal.pone.0076953","volume":"8","author":"J Beygo","year":"2013","unstructured":"Beygo J, Ammerpohl O, Gritzan D, Heitmann M, Rademacher K, Richter J, Caliebe A, Siebert R, Horsthemke B, Buiting K. Deep Bisulfite Sequencing of Aberrantly Methylated Loci in a Patient with Multiple Methylation Defects. PLoS One. 2013;8(10):e76953. doi:10.1371\/journal.pone.0076953.","journal-title":"PLoS One"},{"issue":"18","key":"1380_CR2","doi-asserted-by":"publisher","first-page":"8511","DOI":"10.1158\/0008-5472.CAN-07-1016","volume":"67","author":"K Taylor","year":"2007","unstructured":"Taylor K, Kramer R, Davis J, Guo J, Duff D, Xu D, Caldwell C, Shi H. Ultradeep Bisulfite Sequencing Analysis of DNA Methylation Patterns in Multiple Gene Promoters by 454 Sequencing. Cancer Res. 2007;67(18):8511\u20138. doi:10.1158\/0008-5472.can-07-1016.","journal-title":"Cancer Res"},{"issue":"4","key":"1380_CR3","doi-asserted-by":"publisher","first-page":"561","DOI":"10.2217\/epi.10.32","volume":"2","author":"T Mikeska","year":"2010","unstructured":"Mikeska T, Candiloro I, Dobrovic A. The implications of heterogeneous DNA methylation for the accurate quantification of methylation. Epigenomics. 2010;2(4):561\u201373. doi:10.2217\/epi.10.32.","journal-title":"Epigenomics"},{"issue":"11","key":"1380_CR4","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1038\/ng.2442","volume":"44","author":"G Landan","year":"2012","unstructured":"Landan G, Cohen N, Mukamel Z, Bar A, Molchadsky A, Brosh R, Horn-Saban S, Zalcenstein D, Goldfinger N, Zundelevich A, et al. Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nat Genet. 2012;44(11):1207\u201314. doi:10.1038\/ng.2442.","journal-title":"Nat Genet"},{"issue":"5 Part 2","key":"1380_CR5","doi-asserted-by":"publisher","first-page":"30R","DOI":"10.1203\/pdr.0b013e31804575f7","volume":"61","author":"D Dolinoy","year":"2007","unstructured":"Dolinoy D, Das R, Weidman J, Jirtle R. Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases. Pediatr Res. 2007;61(5 Part 2):30R\u20137R. doi:10.1203\/pdr.0b013e31804575f7.","journal-title":"Pediatr Res"},{"issue":"6","key":"1380_CR6","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.tree.2004.03.034","volume":"19","author":"S Kalisz","year":"2004","unstructured":"Kalisz S, Purugganan M. Epialleles via DNA methylation: consequences for plant evolution. Trends Ecol Evol. 2004;19(6):309\u201314. doi:10.1016\/j.tree.2004.03.034.","journal-title":"Trends Ecol Evol"},{"issue":"1","key":"1380_CR7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/2047-217X-1-7","volume":"1","author":"D McDonald","year":"2012","unstructured":"McDonald D, Clemente J, Kuczynski J, Rideout J, Stombaugh J, Wendel D, Wilke A, Huse S, Hufnagle J, Meyer F, et al. The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome. GigaScience. 2012;1(1):7. doi:10.1186\/2047-217x-1-7.","journal-title":"GigaScience"},{"issue":"5","key":"1380_CR8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","volume":"7","author":"J Caporaso","year":"2010","unstructured":"Caporaso J, Kuczynski J, Stombaugh J, Bittinger K, Bushman F, Costello E, Fierer N, Pe\u00f1a A, Goodrich J, Gordon J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335\u20136. doi:10.1038\/nmeth.f.303.","journal-title":"Nat Methods"},{"issue":"1","key":"1380_CR9","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2105-10-421","volume":"10","author":"C Camacho","year":"2009","unstructured":"Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden T. BLAST+: architecture and applications. BMC Bioinformatics. 2009;10(1):421. doi:10.1186\/1471-2105-10-421.","journal-title":"BMC Bioinformatics"},{"issue":"5","key":"1380_CR10","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1093\/bioinformatics\/btt593","volume":"30","author":"J Zhang","year":"2013","unstructured":"Zhang J, Kobert K, Flouri T, Stamatakis A. PEAR: a fast and accurate Illumina Paired-End reAd mergeR. Bioinformatics. 2013;30(5):614\u201320. doi:10.1093\/bioinformatics\/btt593.","journal-title":"Bioinformatics"},{"issue":"6","key":"1380_CR11","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","volume":"27","author":"R Schmieder","year":"2011","unstructured":"Schmieder R, Edwards R. Quality control and preprocessing of metagenomic datasets. Bioinformatics. 2011;27(6):863\u20134. doi:10.1093\/bioinformatics\/btr026.","journal-title":"Bioinformatics"},{"issue":"7382","key":"1380_CR12","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nature10738","volume":"481","author":"L Ding","year":"2012","unstructured":"Ding L, Ley T, Larson D, Miller C, Koboldt D, Welch J, Ritchey J, Young M, Lamprecht T, McLellan M, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506\u201310. doi:10.1038\/nature10738.","journal-title":"Nature"},{"key":"1380_CR13","doi-asserted-by":"publisher","unstructured":"Pavlopoulos OA, Pavloudi C, Polymenakou P, Papanikolaou N, Kotoulas G, Arvanitidis C, Iliopoulos I. Metagenomics: Tools and Insights for Analyzing Next-Generation Sequencing Data Derived from Biodiversity Studies. BBI. 2015;75: doi:10.4137\/bbi.s12462","DOI":"10.4137\/bbi.s12462"},{"key":"1380_CR14","doi-asserted-by":"publisher","unstructured":"Wong N, Pope B, Candiloro I, Korbie D, Trau M, Wong S, Mikeska T, Zhang X, Pitman M, Eggers S, et al. MethPat: a tool for the analysis and visualisation of complex methylation patterns obtained by massively parallel sequencing. BMC Bioinformatics. 2016;17(1): doi:10.1186\/s12859-016-0950-8","DOI":"10.1186\/s12859-016-0950-8"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1380-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-016-1380-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1380-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T18:21:34Z","timestamp":1706811694000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-016-1380-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,25]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["1380"],"URL":"https:\/\/doi.org\/10.1186\/s12859-016-1380-3","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,25]]},"assertion":[{"value":"17 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"484"}}