Cited by 105Epigenetics and DNA MethylationSingle-cell and spatial transcriptomicsGenomics and Chromatin Dynamics

A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution

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Zhu, Tianyu, Liu, Jacklyn, Beck, Stephan, Pan, Sun, Capper, David, Lechner, Matt, Thirlwell, Chrissie, Breeze, Charles E. +1 more·2022·Nature Methods

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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  1. [32]Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell169, 1327–1341 (2017). PMC5680778 28622513

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Authors
Zhu, T., Liu, J., Beck, S., Pan, S., Capper, D., Lechner, M., Thirlwell, C., Breeze, C. E., & Teschendorff, A. E.
Affiliations
  • Shanghai Institute of Nutrition and Health (CN)
  • University College London (GB)
  • German Cancer Research Center (DE)
  • Barts Health NHS Trust (GB)
  • Altius Institute for Biomedical Sciences (US)
Corresponding author
  • Breeze, Charles E.
  • Teschendorff, Andrew E.
Venue
Nature Methods
Published
2022-03
Volume
19
Issue
3
Pages
296-306
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
OpenAlex
W4221136004
Cited by
103
References
99
Citations by year
2026: 14 · 2025: 21 · 2024: 33 · 2023: 26 · 2022: 9
FWCI
7.43
Type
journal article
Language
en
Open access
Locations
  • Nature Methods (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (31970632)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
cell-type resolution, single-cell RNA sequencing, tumor cell of origin, olfactory neuroblastoma, melanoma, schizophrenia, neuronal origin
MeSH terms
Epigenome, Humans, Neurons, CpG Islands, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study, Epigenomics

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