RT Journal Article
SR Electronic
T1 Landscape of CpG methylation of individual repetitive elements
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 018531
DO 10.1101/018531
A1 Yuta Suzuki
A1 Jonas Korlach
A1 Stephen W. Turner
A1 Tatsuya Tsukahara
A1 Junko Taniguchi
A1 Hideaki Yurino
A1 Wei Qu
A1 Jun Yoshimura
A1 Yuji Takahashi
A1 Jun Mitsui
A1 Shoji Tsuji
A1 Hiroyuki Takeda
A1 Shinichi Morishita
YR 2015
UL http://biorxiv.org/content/early/2015/04/24/018531.abstract
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.