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(2022-03-29 23:30):
#paper Zhu T, Liu J, Beck S, Pan S, Capper D, Lechner M, Thirlwell C, Breeze CE, Teschendorff AE. A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution. Nat Methods. 2022 Mar;19(3):296-306. doi: 10.1038/s41592-022-01412-7. Epub 2022 Mar 11. PMID: 35277705; PMCID: PMC8916958.
该文是3月19刚发表在Nat Methods上的一篇文章,文章主要讲的是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针对13种实体组织类型和40种细胞类型定义的DNA甲基化图谱,简单来说就是构建了一个利用DNA甲基化变异解析多种组织中细胞类型。目前单细胞测序主要还是以RNA表达谱为主,因此如何通过甲基化测序来准确预测组织中各种细胞类型还待研究。虽然已经有一些算法例如MehylCIBERSORT,其原理如其名字一样,都是借鉴CIBERSORT的反卷积算法,但根据其原理,只能计算成纤维细胞以及7种免疫细胞的甲基化谱,但不同肿瘤类型的组织中实际情况是更加复杂的。本文作者从多个不同肿瘤组织的单细胞测序数据出发,细胞的marker基因的mRNA表达量与其启动子区域的甲基化成显著反比的位点来定义甲基化marker。可以准确在13种组织类型和40种细胞的高分辨率DNA甲基化图谱。作者基于不同组织的中特异的细胞类型结果,分别做了验证,并且在具体的临床问题(神经细胞瘤和2期黑色素瘤的新预后关联)上,也都有良好的表现。最后作者提供了上述表达谱计算R包,并且该R包也能通过自测数据,在新的组织上构建起特异的细胞类型:https://github.com/ww880412/RPresto ;
遗憾的是,我没成功安装上还,缺少依赖包“presto”。但未找到该包,只有一个RPresto,装上后依然报错,待解决中;
IF:36.100Q1
Nature methods,
2022-03.
DOI: 10.1038/s41592-022-01412-7
PMID: 35277705
PMCID:PMC8916958
A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution
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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.
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