vmrseq

github.com/nshen7/vmrseq
Idle10updated 12 months ago
R
MIT

High-throughput single-cell measurements of DNA methylation allows studying inter-cellular epigenetic heterogeneity, but this task faces the challenges of sparsity and noise. We present vmrseq, a statistical method that overcomes these challenges and identifies variably methylated regions accurately and robustly.

Sourced from

  • Bioconductorvmrseq
  • GitHubgithub.com/nshen7/vmrseq

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This package implements an approach for scanning the genome to detect and perform accurate inference on differentially methylated regions from Whole Genome Bisulfite Sequencing data. The method is based on comparing detected regions to a pooled null distribution, that can be implemented even when as few as two samples per population are available. Region-level statistics are obtained by fitting a generalized least squares (GLS) regression model with a nested autoregressive correlated error structure for the effect of interest on transformed methylation proportions.

Recent advances in single cell/nucleus transcriptomic technology has enabled collection of cohort-scale datasets to study cell type specific gene expression differences associated disease state, stimulus, and genetic regulation. The scale of these data, complex study designs, and low read count per cell mean that characterizing cell type specific molecular mechanisms requires a user-frieldly, purpose-build analytical framework. We have developed the dreamlet package that applies a pseudobulk approach and fits a regression model for each gene and cell cluster to test differential expression across individuals associated with a trait of interest. Use of precision-weighted linear mixed models enables accounting for repeated measures study designs, high dimensional batch effects, and varying sequencing depth or observed cells per biosample.

This package implements functions for calling methylation for all cytosines in the genome.