The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Identification of differentially methylated cell types in epigenome-wide association studies
Open accessAbstract
An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC (https://github.com/sjczheng/EpiDISH), which can identify differentially methylated positions and the specific cell type(s) driving the differential methylation. We validated CellDMC on in silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide association and cancer epigenome studies. CellDMC achieved over 90% sensitivity and specificity in scenarios where current state-of-the-art methods did not identify differential methylation. By applying CellDMC to an EWAS performed in buccal swabs, we identified smoking-associated differentially methylated positions occurring in the epithelial compartment, which we validated in smoking-related lung cancer. CellDMC may be useful in the identification of causal DNA-methylation alterations in disease. CellDMC finds cell type–specific differential methylation in mixtures of cells, including epithelial tissues, and scenarios in which methylation changes in opposite directions in different cell types.
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Cites
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Cited by
DNA hypermethylation in disease: mechanisms and clinical relevance
Ehrlich, M. (2019) · Epigenetics · doi:10.1080/15592294.2019.1638701 · Cited by 373
Zhu, T., Liu, J., Beck, S., Pan, S., Capper, D., Lechner, M., Thirlwell, C., Breeze, C. E., & Teschendorff, A. E. (2022) · Nature Methods · doi:10.1038/s41592-022-01412-7 · Cited by 103
Self-citationDistinct sex-specific DNA methylation differences in Alzheimer’s disease
C. Silva, T., Zhang, W., Young, J. I., Gomez, L., Schmidt, M. A., Varma, A., Chen, X. S., Martin, E. R., & Wang, L. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01070-z · Cited by 33
“Immune cell-type proportions were estimated using the R/Bioconductor package EpiDISH [41] and Xcell [54] R software (https:// github.”
MethodInfluentialWang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28
Julià, A., Gómez, A., López-Lasanta, M., Blanco, F., Erra, A., Fernández-Nebro, A., Mas, A. J., Pérez-García, C., Vivar, M. L. G., Sánchez-Fernández, S., et al. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.104053 · Cited by 24
Metadata
- Authors
- Zheng, S. C., Breeze, C. E., Beck, S., & Teschendorff, A. E.
- Venue
- Nature Methods
- Published
- 2018-11-30
- Volume
- 15
- Issue
- 12
- Pages
- 1059-1066
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2919386822
- Cited by
- 320
- References
- 45
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
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