000128189 001__ 128189 000128189 005__ 20240228135046.0 000128189 0247_ $$2doi$$a10.1002/sim.6251 000128189 0247_ $$2pmid$$apmid:25042556 000128189 0247_ $$2ISSN$$a0277-6715 000128189 0247_ $$2ISSN$$a1097-0258 000128189 0247_ $$2altmetric$$aaltmetric:2486618 000128189 037__ $$aDKFZ-2017-04207 000128189 041__ $$aeng 000128189 082__ $$a610 000128189 1001_ $$0P:(DE-He78)609d3f1c1420bf59b2332eeab889cb74$$aSaadati, Maral$$b0$$eFirst author$$udkfz 000128189 245__ $$aStatistical challenges of high-dimensional methylation data. 000128189 260__ $$aChichester [u.a.]$$bWiley$$c2014 000128189 3367_ $$2DRIVER$$aarticle 000128189 3367_ $$2DataCite$$aOutput Types/Journal article 000128189 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1523608964_20073 000128189 3367_ $$2BibTeX$$aARTICLE 000128189 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000128189 3367_ $$00$$2EndNote$$aJournal Article 000128189 520__ $$aWith the fast growing field of epigenetics comes the need to better understand the intricacies of DNA methylation data analysis. High-throughput profiling using techniques, such as Illumina's BeadArray assay, enable the quantitative assessment of methylation. Challenges arise from the fact that resulting methylation levels (so-called beta values) are proportions between 0 and 1, often from an asymmetric, bimodal distribution with peaks close to 0 and 1. Therefore, the majority of standard statistical approaches do not apply. The logit transformation into so-called M-values is a common approach to circumvent this problem and aims to allow the use of common statistical methods. However, it can be observed that the transformation from beta to M-values does not necessarily result in an approximately homoscedastic distribution. Often, bimodality, asymmetry and heteroscedasticity are conserved even after transformation. We give an overview and discussion of methods suggested in the recent years that attempt to address the characteristics of methylation data in univariate screening settings. In order to identify 'differential' methylation with respect to covariates of interest while adjusting for confounders, we compare parametric methods, such as linear and beta regression, and nonparametric methods, such as rank-based regression. Our goal is to sensitise researchers to the challenges and issues that arise from this type of data as well as to present possible solutions. 000128189 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0 000128189 588__ $$aDataset connected to CrossRef, PubMed, 000128189 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b1$$eLast author$$udkfz 000128189 773__ $$0PERI:(DE-600)1491221-1$$a10.1002/sim.6251$$gVol. 33, no. 30, p. 5347 - 5357$$n30$$p5347 - 5357$$tStatistics in medicine$$v33$$x0277-6715$$y2014 000128189 909CO $$ooai:inrepo02.dkfz.de:128189$$pVDB 000128189 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)609d3f1c1420bf59b2332eeab889cb74$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000128189 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000128189 9131_ $$0G:(DE-HGF)POF3-313$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vCancer risk factors and prevention$$x0 000128189 9141_ $$y2014 000128189 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000128189 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000128189 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000128189 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSTAT MED : 2015 000128189 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000128189 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000128189 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000128189 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000128189 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000128189 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000128189 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000128189 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000128189 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lBiostatistik$$x0 000128189 980__ $$ajournal 000128189 980__ $$aVDB 000128189 980__ $$aI:(DE-He78)C060-20160331 000128189 980__ $$aUNRESTRICTED