{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:14Z","timestamp":1772138054728,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex"},{"DOI":"10.13039\/501100000269","name":"Economic and Social Research Council","doi-asserted-by":"publisher","award":["ES\/M008592\/1"],"award-info":[{"award-number":["ES\/M008592\/1"]}],"id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R005176\/1"],"award-info":[{"award-number":["MR\/R005176\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000269","name":"Economic and Social Research Council","doi-asserted-by":"publisher","award":["ES\/M010236\/1"],"award-info":[{"award-number":["ES\/M010236\/1"]}],"id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/P017487\/1"],"award-info":[{"award-number":["EP\/P017487\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/R02572X\/1"],"award-info":[{"award-number":["EP\/R02572X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/V000462\/1"],"award-info":[{"award-number":["EP\/V000462\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/V034111\/1"],"award-info":[{"award-number":["EP\/V034111\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010046","name":"University of Essex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Data normalization is an essential step to reduce technical variation within and between arrays. Due to the different karyotypes and the effects of X chromosome inactivation, females and males exhibit distinct methylation patterns on sex chromosomes; thus, it poses a significant challenge to normalize sex chromosome data without introducing bias. Currently, existing methods do not provide unbiased solutions to normalize sex chromosome data, usually, they just process autosomal and sex chromosomes indiscriminately.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we demonstrate that ignoring this sex difference will lead to introducing artificial sex bias, especially for thousands of autosomal CpGs. We present a novel two-step strategy (interpolatedXY) to address this issue, which is applicable to all quantile-based normalization methods. By this new strategy, the autosomal CpGs are first normalized independently by conventional methods, such as funnorm or dasen; then the corrected methylation values of sex chromosome-linked CpGs are estimated as the weighted average of their nearest neighbors on autosomes. The proposed two-step strategy can also be applied to other non-quantile-based normalization methods, as well as other array-based data types. Moreover, we propose a useful concept: the sex explained fraction of variance, to quantitatively measure the normalization effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The proposed methods are available by calling the function \u2018adjustedDasen\u2019 or \u2018adjustedFunnorm\u2019 in the latest wateRmelon package (https:\/\/github.com\/schalkwyk\/wateRmelon), with methods compatible with all the major workflows, including minfi.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac436","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T11:53:35Z","timestamp":1656590015000},"page":"3950-3957","source":"Crossref","is-referenced-by-count":18,"title":["InterpolatedXY: a two-step strategy to normalize DNA methylation microarray data avoiding sex bias"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-0734","authenticated-orcid":false,"given":"Yucheng","family":"Wang","sequence":"first","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler J","family":"Gorrie-Stone","sequence":"additional","affiliation":[{"name":"Diamond Light Source Ltd. , Oxfordshire OX11 0DE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia A","family":"Grant","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria D","family":"Andrayas","sequence":"additional","affiliation":[{"name":"Institute for Social and Economic Research, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1030-8311","authenticated-orcid":false,"given":"Xiaojun","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus D","family":"McDonald-Maier","sequence":"additional","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard C","family":"Schalkwyk","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Essex , Colchester CO4 3SQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"2023041408492611200_","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ygeno.2011.07.007","article-title":"High density DNA methylation array with single CpG site resolution","volume":"98","author":"Bibikova","year":"2011","journal-title":"Genomics"},{"key":"2023041408492611200_","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1093\/hmg\/ddu564","article-title":"Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation","volume":"24","author":"Cotton","year":"2015","journal-title":"Hum. 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