Acharya Sonia N, Nichols Ruth V, Rylaarsdam Lauren E, O'Connell Brendan L, Braun Theodore P, Adey Andrew C
Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
Cancer Early Detection Advanced Research Center, Oregon Health and Science University, Portland, OR, USA.
bioRxiv. 2023 Jul 14:2023.07.12.548718. doi: 10.1101/2023.07.12.548718.
DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Sufficient off-target coverage further enables the production of near-complete methylomes for individual cell types. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).
DNA甲基化是哺乳动物表观基因组的关键组成部分，在发育、疾病及其他过程中发挥调节作用。目前，可靠的高通量单细胞DNA甲基化检测方法（sciMET）已经可行；然而，DNA甲基化的全基因组性质导致每个细胞的测序负担较重。在此，我们利用sciMET进行靶向富集，以使用显著更少的序列读数（sciMET-cap）为每个细胞捕获足够的信息用于细胞类型分类。足够的脱靶覆盖进一步使得能够为单个细胞类型生成近乎完整的甲基化组。我们对人外周血单核细胞和大脑（额中回）的sciMET-cap进行了表征。
