Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Bioinformatics. 2013 Oct 15;29(20):2645-6. doi: 10.1093/bioinformatics/btt459. Epub 2013 Aug 21.
The two major epigenetic modifications of cytosines, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), coexist with each other in a range of mammalian cell populations. Increasing evidence points to important roles of 5-hmC in demethylation of 5-mC and epigenomic regulation in development. Recently developed experimental methods allow direct single-base profiling of either 5-hmC or 5-mC. Meaningful analyses seem to require combining these experiments with bisulfite sequencing, but doing so naively produces inconsistent estimates of 5-mC or 5-hmC levels.
We present a method to jointly model read counts from bisulfite sequencing, oxidative bisulfite sequencing and Tet-Assisted Bisulfite sequencing, providing simultaneous estimates of 5-hmC and 5-mC levels that are consistent across experiment types.
胞嘧啶的两种主要表观遗传修饰，5-甲基胞嘧啶（5-mC）和 5-羟甲基胞嘧啶（5-hmC），在多种哺乳动物细胞群体中并存。越来越多的证据表明，5-hmC 在 5-mC 的去甲基化和发育中的表观基因组调控中起着重要作用。最近开发的实验方法允许直接对 5-hmC 或 5-mC 进行单碱基谱分析。有意义的分析似乎需要将这些实验与亚硫酸氢盐测序相结合，但这样做会导致 5-mC 或 5-hmC 水平的估计不一致。
我们提出了一种联合建模方法，用于对亚硫酸氢盐测序、氧化亚硫酸氢盐测序和 Tet 辅助亚硫酸氢盐测序的读取计数进行建模，为 5-hmC 和 5-mC 水平提供了跨实验类型一致的同时估计。
