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MethylCal: Bayesian Calibration of Methylation Levels
dc.contributor.author | Ochoa Ruiz, Eguzkine | |
dc.contributor.author | Zuber, Verena | |
dc.contributor.author | Fernández Jiménez, Nora | |
dc.contributor.author | Bilbao Catalá, José Ramón | |
dc.contributor.author | Clark, Graeme R. | |
dc.contributor.author | Maher, Eamonn R. | |
dc.contributor.author | Bottolo, Leonardo | |
dc.date.accessioned | 2019-11-28T09:51:52Z | |
dc.date.available | 2019-11-28T09:51:52Z | |
dc.date.issued | 2019-08-22 | |
dc.identifier.citation | Nucleic Acids Research 47(14) : (2019) // Article ID e81 | es_ES |
dc.identifier.issn | 0305-1048 | |
dc.identifier.issn | 1362-4962 | |
dc.identifier.uri | http://hdl.handle.net/10810/36605 | |
dc.description.abstract | Bisulfite amplicon sequencing has become the primary choice for single-base methylation quantification of multiple targets in parallel. The main limitation of this technology is a preferential amplification of an allele and strand in the PCR due to methylation state. This effect, known as PCR bias', causes inaccurate estimation of the methylation levels and calibration methods based on standard controls have been proposed to correct for it. Here, we present a Bayesian calibration tool, MethylCal, which can analyse jointly all CpGs within a CpG island (CGI) or a Differentially Methylated Region (DMR), avoiding one-at-a-time' CpG calibration. This enables more precise modeling of the methylation levels observed in the standard controls. It also provides accurate predictions of the methylation levels not considered in the controlled experiment, a feature that is paramount in the derivation of the corrected methylation degree. We tested the proposed method on eight independent assays (two CpG islands and six imprinting DMRs) and demonstrated its benefits, including the ability to detect outliers. We also evaluated MethylCal's calibration in two practical cases, a clinical diagnostic test on 18 patients potentially affected by Beckwith-Wiedemann syndrome, and 17 individuals with celiac disease. The calibration of the methylation levels obtained by MethylCal allows a clearer identification of patients undergoing loss or gain of methylation in borderline cases and could influence further clinical or treatment decisions. | es_ES |
dc.description.sponsorship | Alan Turing Institute under the Engineering and Physical Sciences Research Council [EP/N510129/1 to L.B.]; UK Medical Research Council [MC UU 00002/7 to V.Z.]; Wellcome Trust and the Royal Society [204623/Z/16/Z to V.Z.]; National Institute of Health Research (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre) (to E.R.M.). The University of Cambridge has received salary support (E.R.M.) from the NHS in the East of England through the Clinical Academic Reserve. Funding for open access charge: Cambridge Open Access: https://www.openaccess.cam.ac.uk/. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | DNA methylation | es_ES |
dc.subject | PCR bias | es_ES |
dc.subject | prediction | es_ES |
dc.subject | regression | es_ES |
dc.subject | inference | es_ES |
dc.title | MethylCal: Bayesian Calibration of Methylation Levels | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://academic.oup.com/nar/article/47/14/e81/5485069 | es_ES |
dc.identifier.doi | 10.1093/nar/gkz325 | |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |
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