A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution.
Nat Methods
; 19(3): 296-306, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-35277705
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Metilación de ADN
/
Epigenoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Methods
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2022
Tipo del documento:
Article
País de afiliación:
China