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Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology

By Elior Rahmani, Regev Schweiger, Brooke Rhead, Lindsey A. Criswell, Lisa F. Barcellos, Eleazar Eskin, Saharon Rosset, Sriram Sankararaman, Eran Halperin

Posted 07 Oct 2018
bioRxiv DOI: 10.1101/437368 (published DOI: 10.1038/s41467-019-11052-9)

High costs and technical limitations of cell sorting and single-cell techniques currently restrict the collection of large-scale, cell-type-specific DNA methylation data. This, in turn, impedes our ability to tackle key biological questions that pertain to variation within a population, such as identification of disease-associated genes at a cell-type-specific resolution. Here, we show mathematically and empirically that cell-type-specific methylation levels of an individual can be learned from its tissue-level bulk data, conceptually emulating the case where the individual has been profiled with a single-cell resolution and then signals were aggregated in each cell population separately. Provided with this unprecedented way to perform powerful large-scale epigenetic studies with cell-type-specific resolution, we revisit previous studies with tissue-level bulk methylation and reveal novel associations with leukocyte composition in blood and with rheumatoid arthritis. For the latter, we further show consistency with validation data collected from sorted leukocyte sub-types. Corresponding software is available from: <https://github.com/cozygene/TCA>.

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