中国科学院上海营养与健康研究所Andrew E. Teschendorff、英国伦敦大学学院Charles E. Breeze等研究人员合作绘制出一个泛组织的DNA甲基化图谱，能够以细胞类型分辨率进行人类组织甲基化组的计算拆解。2022年3月11日，《自然—方法学》杂志在线发表了这项成果。
研究人员利用组织特异性单细胞RNA测序数据集的高分辨率特性，构建了一个为13种实体组织类型和40种细胞类型定义的DNA甲基化图谱。研究人员在独立的体细胞和单核DNA甲基化数据集中全面验证了这个图集。研究人员证明，它能正确预测不同癌症类型的起源细胞，并在嗅觉神经母细胞瘤和2期黑色素瘤中发现新的预后关联。在大脑中，该图谱预测了精神分裂症的神经元起源，神经元特异性差异DNA甲基化富集于相应的全基因组关联研究风险位点。总之，DNA甲基化图谱能够以高细胞分辨率分解13种不同的人类组织类型，为改善表观遗传学数据的解释铺平了道路。
据介绍，大量组织的DNA甲基组代表了许多不同类型细胞的平均值，阻碍了人们对细胞类型对疾病发展特定贡献的理解。由于单细胞甲基组学不能扩展到大群个体，因此需要有成本效益的计算解决方案，但目前的方法仅限于血液等组织。
附：英文原文
Title: A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution
Author: Zhu, Tianyu, Liu, Jacklyn, Beck, Stephan, Pan, Sun, Capper, David, Lechner, Matt, Thirlwell, Chrissie, Breeze, Charles E., Teschendorff, Andrew E.
Issue&Volume: 2022-03-11
Abstract: Bulk-tissue DNA methylomes represent an average over many different cell types, hampering our understanding of cell-type-specific contributions to disease development. As single-cell methylomics is not scalable to large cohorts of individuals, cost-effective computational solutions are needed, yet current methods are limited to tissues such as blood. Here we leverage the high-resolution nature of tissue-specific single-cell RNA-sequencing datasets to construct a DNA methylation atlas defined for 13 solid tissue types and 40 cell types. We comprehensively validate this atlas in independent bulk and single-nucleus DNA methylation datasets. We demonstrate that it correctly predicts the cell of origin of diverse cancer types and discovers new prognostic associations in olfactory neuroblastoma and stage 2 melanoma. In brain, the atlas predicts a neuronal origin for schizophrenia, with neuron-specific differential DNA methylation enriched for corresponding genome-wide association study risk loci. In summary, the DNA methylation atlas enables the decomposition of 13 different human tissue types at a high cellular resolution, paving the way for an improved interpretation of epigenetic data. This resource presents an in silico generated DNA methylation atlas that can be used for cell-type deconvolution of human tissues.
DOI: 10.1038/s41592-022-01412-7
Source: https://www.nature.com/articles/s41592-022-01412-7
Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex
本期文章：《自然—方法学》：Online/在线发表
