Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes
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Author
Beaulaurier, John
Zhang, Xue-Song
Zhu, Shijia
Sebra, Robert
Rosenbluh, Chaggai
Deikus, Gintaras
Shen, Nan
Munera, Diana
Chess, Andrew
Blaser, Martin J.
Schadt, Eric E.
Fang, Gang
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https://doi.org/10.1038/ncomms8438Metadata
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Beaulaurier, J., X. Zhang, S. Zhu, R. Sebra, C. Rosenbluh, G. Deikus, N. Shen, et al. 2015. “Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes.” Nature Communications 6 (1): 7438. doi:10.1038/ncomms8438. http://dx.doi.org/10.1038/ncomms8438.Abstract
Beyond its role in host defense, bacterial DNA methylation also plays important roles in the regulation of gene expression, virulence and antibiotic resistance. Bacterial cells in a clonal population can generate epigenetic heterogeneity to increase population-level phenotypic plasticity. Single molecule, real-time (SMRT) sequencing enables the detection of N6-methyladenine and N4-methylcytosine, two major types of DNA modifications comprising the bacterial methylome. However, existing SMRT sequencing-based methods for studying bacterial methylomes rely on a population-level consensus that lacks the single-cell resolution required to observe epigenetic heterogeneity. Here, we present SMALR (single-molecule modification analysis of long reads), a novel framework for single molecule-level detection and phasing of DNA methylation. Using seven bacterial strains, we show that SMALR yields significantly improved resolution and reveals distinct types of epigenetic heterogeneity. SMALR is a powerful new tool that enables de novo detection of epigenetic heterogeneity and empowers investigation of its functions in bacterial populations.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490391/pdf/Terms of Use
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