title: Assessing Cell-to-Cell DNA Methylation Variability on Individual Long Reads.
abstract: Understanding cell-to-cell variability in cytosine methylation is essential for understanding cellular perturbation and its molecular machinery. However, conventional methylation studies have focused on the differences in the average levels between cell types while overlooking methylation heterogeneity within cell types. Little information has been uncovered using recent single-cell methods because of either technical limitations or the great labor required to process many single cells. Here, we report the highly efficient detection of cell-to-cell DNA methylation variability in liver tissue, based on comparing the methylation status of adjacent CpG sites on long sequencing reads. This method provides abundant methylation linkage information and enables genome-wide estimation of cell-to-cell variability. We observed repressed methylation variability in hypomethylated regions compared with the variability in hypomethylated regions across the genome, which we confirmed using public human sperm data. A gradual change in methylation status at the boundaries of hypomethylated regions was observed for the first time. This approach allows the concise, comprehensive assessment of cell-to-cell DNA methylation variability.
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Japan.|CREST, JST, 5-3 Yonbancho, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Biological Sciences, Graduate School of Science, the University of Tokyo, Tokyo, Japan.|Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Biological Sciences, Graduate School of Science, the University of Tokyo, Tokyo, Japan.|CREST, JST, 5-3 Yonbancho, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yurino
authors.affiliation: Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Biological Sciences, Graduate School of Science, the University of Tokyo, Tokyo, Japan.|CREST, JST, 5-3 Yonbancho, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Japan.|CREST, JST, 5-3 Yonbancho, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans