vmrseq: probabilistic modeling of single-cell methylation heterogeneity

Abstract Single-cell DNA methylation measurements reveal genome-scale inter-cellular epigenetic heterogeneity, but extreme sparsity and noise challenges rigorous analysis. Previous methods to detect variably methylated regions (VMRs) have relied on predefined regions or sliding windows and report re...

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Main Authors: Ning Shen, Keegan Korthauer
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Genome Biology
Subjects:
Online Access:https://doi.org/10.1186/s13059-024-03457-7
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author Ning Shen
Keegan Korthauer
author_facet Ning Shen
Keegan Korthauer
author_sort Ning Shen
collection DOAJ
description Abstract Single-cell DNA methylation measurements reveal genome-scale inter-cellular epigenetic heterogeneity, but extreme sparsity and noise challenges rigorous analysis. Previous methods to detect variably methylated regions (VMRs) have relied on predefined regions or sliding windows and report regions insensitive to heterogeneity level present in input. We present vmrseq, a statistical method that overcomes these challenges to detect VMRs with increased accuracy in synthetic benchmarks and improved feature selection in case studies. vmrseq also highlights context-dependent correlations between methylation and gene expression, supporting previous findings and facilitating novel hypotheses on epigenetic regulation. vmrseq is available at https://github.com/nshen7/vmrseq .
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institution Kabale University
issn 1474-760X
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publishDate 2024-12-01
publisher BMC
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spelling doaj-art-f000009323f248df9c9e6badf7c59c3b2025-01-05T12:31:57ZengBMCGenome Biology1474-760X2024-12-0125112710.1186/s13059-024-03457-7vmrseq: probabilistic modeling of single-cell methylation heterogeneityNing Shen0Keegan Korthauer1Department of Statistics, University of British ColumbiaDepartment of Statistics, University of British ColumbiaAbstract Single-cell DNA methylation measurements reveal genome-scale inter-cellular epigenetic heterogeneity, but extreme sparsity and noise challenges rigorous analysis. Previous methods to detect variably methylated regions (VMRs) have relied on predefined regions or sliding windows and report regions insensitive to heterogeneity level present in input. We present vmrseq, a statistical method that overcomes these challenges to detect VMRs with increased accuracy in synthetic benchmarks and improved feature selection in case studies. vmrseq also highlights context-dependent correlations between methylation and gene expression, supporting previous findings and facilitating novel hypotheses on epigenetic regulation. vmrseq is available at https://github.com/nshen7/vmrseq .https://doi.org/10.1186/s13059-024-03457-7DNA methylationSingle-cell bisulfite sequencingEpigenetic heterogeneityHidden Markov model
spellingShingle Ning Shen
Keegan Korthauer
vmrseq: probabilistic modeling of single-cell methylation heterogeneity
Genome Biology
DNA methylation
Single-cell bisulfite sequencing
Epigenetic heterogeneity
Hidden Markov model
title vmrseq: probabilistic modeling of single-cell methylation heterogeneity
title_full vmrseq: probabilistic modeling of single-cell methylation heterogeneity
title_fullStr vmrseq: probabilistic modeling of single-cell methylation heterogeneity
title_full_unstemmed vmrseq: probabilistic modeling of single-cell methylation heterogeneity
title_short vmrseq: probabilistic modeling of single-cell methylation heterogeneity
title_sort vmrseq probabilistic modeling of single cell methylation heterogeneity
topic DNA methylation
Single-cell bisulfite sequencing
Epigenetic heterogeneity
Hidden Markov model
url https://doi.org/10.1186/s13059-024-03457-7
work_keys_str_mv AT ningshen vmrseqprobabilisticmodelingofsinglecellmethylationheterogeneity
AT keegankorthauer vmrseqprobabilisticmodelingofsinglecellmethylationheterogeneity