Abstract
Determining the methylation state of regions with high copy numbers is challenging for second-generation sequencing because the read length is insufficient to map uniquely, especially when repetitive regions are long and nearly identical to each other. Single-molecule real-time sequencing is a promising method for observing such regions, because it is not vulnerable to guanine and cytosine (GC) bias, it performs long read lengths, and its kinetic information is sensitive to DNA modifications. Combining the kinetic information for neighboring CpG sites increases the confidence in identifying the methylation states of those sites when they are correlated. This method allows us to comprehensively evaluate the methylation states for nearly identical (>99.8%) active transposons 4682bp in length in the medaka-fish genome. In personal human genomes, it is capable of characterizing the landscape of the methylation status of repetitive elements, such as long interspersed nuclear elements and long terminal repeats.
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