Methods for discovering genomic loci exhibiting complex patterns of differential methylation [article]

Thomas J Hardcastle
2015 bioRxiv   pre-print
Cytosine methylation is widespread in most eukaryotic genomes and is known to play a substantial role in various regulatory pathways. Unmethylated cytosines may be converted to uracil through the addition of sodium bisulphite, allowing genome-wide quantification of cytosine methylation via high-throughput sequencing. The data thus acquired allows the discovery of methylation 'loci'; contiguous regions of methylation consistently methylated across biological replicates. The mapping of these loci
more » ... pping of these loci allows for associations with other genomic factors to be identified, and for analyses of differential methylation to take place. The segmentSeq R package is extended to identify methylation loci from high-throughput sequencing data from multiple experimental conditions. A statistical model is then developed that accounts for biological replication and variable rates of non-conversion of cytosines in each sample to compute posterior likelihoods of methylation at each locus within an empirical Bayesian framework. The same model is used as a basis for analysis of differential methylation between multiple experimental conditions with the baySeq R package. We demonstrate this method through an analysis of data derived from Dicer-like mutants in Arabidopsis that reveals complex interactions between the different Dicer-like mutants and their methylation pathways. We also show in simulation studies that this approach can be significantly more powerful in the detection of differential methylation than existing methods.
doi:10.1101/021436 fatcat:hbbzctm2grcbzp66jffkayaxzq