Bisulfite conversion of genomic DNA combined with next-generation sequencing (BS-seq) is widely used to measure the methylation state of a whole genome, the methylome, at single-base resolution. However, analysis of BS-seq data still poses a considerable challenge. Here we summarize the challenges of BS-seq mapping as they apply to both base and color-space data. We also explore the effect of sequencing errors and contaminants on inferred methylation levels and recommend the most appropriate way to analyze this type of data.
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This work was funded by the Biotechnology and Biological Sciences Research Council, UK. A.F. and B.K. received infrastructure support from the Deutsche Forschungsgemeinschaft Excellence Cluster 'Inflammation at Interfaces'.
The authors declare no competing financial interests.
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Krueger, F., Kreck, B., Franke, A. et al. DNA methylome analysis using short bisulfite sequencing data. Nat Methods 9, 145–151 (2012). https://doi.org/10.1038/nmeth.1828
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