Detection and accurate false discovery rate control of differentially methylated regions from whole genome bisulfite sequencing

Biostatistics
Keegan KorthauerRafael A Irizarry

Abstract

With recent advances in sequencing technology, it is now feasible to measure DNA methylation at tens of millions of sites across the entire genome. In most applications, biologists are interested in detecting differentially methylated regions, composed of multiple sites with differing methylation levels among populations. However, current computational approaches for detecting such regions do not provide accurate statistical inference. A major challenge in reporting uncertainty is that a genome-wide scan is involved in detecting these regions, which needs to be accounted for. A further challenge is that sample sizes are limited due to the costs associated with the technology. We have developed a new approach that overcomes these challenges and assesses uncertainty for differentially methylated regions in a rigorous manner. Region-level statistics are obtained by fitting a generalized least squares regression model with a nested autoregressive correlated error structure for the effect of interest on transformed methylation proportions. We develop an inferential approach, based on a pooled null distribution, that can be implemented even when as few as two samples per population are available. Here, we demonstrate the advantages o...Continue Reading

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Citations

Apr 24, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Benjamin I LauferJanine M LaSalle
Oct 19, 2019·Human Molecular Genetics·S Jesse LopezJanine M LaSalle
Mar 13, 2020·The New Phytologist·Mohammad Reza AtighiTina Kyndt
Jun 3, 2020·Bioinformatics·Viivi Halla-Aho, Harri Lähdesmäki
Jul 22, 2020·Nature Genetics·Mark M PomerantzMatthew L Freedman
Jun 4, 2020·Epigenetics & Chromatin·Stephany OrjuelaMark D Robinson
May 3, 2020·BMC Bioinformatics·Marius WösteChristopher Schröder
Feb 23, 2019·Genome Biology·Krishna ChoudharySharon Aviran
Jun 23, 2021·Nature Communications·Laura SantiniMartin Leeb
Jul 19, 2021·BMC Genomics·Stefan MilosavljevicMark D Robinson
Jul 29, 2021·Nucleic Acids Research·Timothy J PetersSusan J Clark
Aug 10, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Stephany OrjuelaGiancarlo Marra
Aug 23, 2021·Drug and Alcohol Dependence·Adam P VogelGabrielle Todd
Nov 4, 2021·Communications Biology·Matteo BenelliFrancesca Demichelis
Dec 17, 2021·Nature Communications·Haiyang GuoSteven P Balk

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