LuxHS: DNA Methylation Analysis with Spatially Varying Correlation Structure

Viivi Halla-aho, Harri Lähdesmäki

Abstract: Bisulfite sequencing (BS-seq) is a popular method for measuring DNA methylation in basepair-resolution. Many BS-seq data analysis tools utilize the assumption of spatial correlation among the neighboring cytosines’ methylation states. While being a fair assumption, most existing methods leave out the possibility of deviation from the spatial correlation pattern. Our approach builds on a method which combines a generalized linear mixed model (GLMM) with a likelihood that is specific for BS-seq data and that incorporates a spatial correlation for methylation levels. We propose a novel technique using a sparsity promoting prior to enable cytosines deviating from the spatial correlation pattern. The method is tested with both simulated and real BS-seq data and compared to other differential methylation analysis tools.