PT  - JOURNAL ARTICLE
AU  - Yuta Suzuki
AU  - Jonas Korlach
AU  - Stephen W. Turner
AU  - Tatsuya Tsukahara
AU  - Junko Taniguchi
AU  - Hideaki Yurino
AU  - Wei Qu
AU  - Jun Yoshimura
AU  - Yuji Takahashi
AU  - Jun Mitsui
AU  - Shoji Tsuji
AU  - Hiroyuki Takeda
AU  - Shinichi Morishita
TI  - Landscape of CpG methylation of individual repetitive elements
AID  - 10.1101/018531
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 018531
4099  - http://biorxiv.org/content/early/2015/04/24/018531.short
4100  - http://biorxiv.org/content/early/2015/04/24/018531.full
AB  - Determining the methylation state of regions with high copy numbers is chal-lenging 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 (SMRT) sequencing is a promising method for observing such regions, because it is not vulnerable to GC bias, it performs long read lengths, and its kinetic information is sensitive to DNA modifications. Here, we propose a novel algorithm that combines the kinetic information for neighboring CpG sites and increases the confidence in identifying the methylation states of those sites when they are correlated. Both the sensitivity and precision of our algorithm were >84% for the genome of an inbred medaka (Oryzias latipes) strain within a practical read coverage of <18-fold. Using this method, we characterized the landscape of the methylation status of repetitive elements, such as LINEs, in the human genome, thereby revealing the strong correlation between CpG density and hypomethylation and detecting hypomethylation hot spots of LTRs and LINEs. We also comprehensively evaluated the methylation states for nearly identical (> 99.8%) active transposons 4682 base pairs (bp) in length in the medaka genome, which were difficult to observe using bisulfite-treated short reads.