sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden

Sonia N Acharya; Ruth V Nichols; Lauren E Rylaarsdam; Brendan L O'Connell; Theodore P Braun; Andrew C Adey

doi:10.1186/s13059-024-03306-7

sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden

Genome Biol. 2024 Jul 10;25(1):186. doi: 10.1186/s13059-024-03306-7.

Authors

Sonia N Acharya^#¹, Ruth V Nichols^#¹, Lauren E Rylaarsdam¹, Brendan L O'Connell^{1

2}, Theodore P Braun^{2

3

4}, Andrew C Adey^{5

6

7

8}

Affiliations

¹ Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
² Cancer Early Detection Advanced Research Center, Oregon Health and Science University, Portland, OR, USA.
³ Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
⁴ Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
⁵ Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA. [email protected].
⁶ Cancer Early Detection Advanced Research Center, Oregon Health and Science University, Portland, OR, USA. [email protected].
⁷ Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. [email protected].
⁸ Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA. [email protected].

^# Contributed equally.

Abstract

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Accumulated off-target coverage enables genome-wide differentially methylated region (DMR) calling for clusters with as few as 115 cells. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).

Keywords: DNA methylation; Epigenetics; Single-cell.

MeSH terms

Brain / metabolism
DNA Methylation*
Epigenomics / methods
High-Throughput Nucleotide Sequencing* / methods
Humans
Leukocytes, Mononuclear / metabolism
Sequence Analysis, DNA / methods
Single-Cell Analysis* / methods

Abstract

MeSH terms

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