Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes

John Beaulaurier, Xue Song Zhang, Shijia Zhu, Robert Sebra, Chaggai Rosenbluh, Gintaras Deikus, Nan Shen, Diana Munera, Matthew K. Waldor, Andrew Chess, Martin J. Blaser, Eric E. Schadt, Gang Fang

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Article number7438
JournalNature communications
Volume6
DOIs
StatePublished - Jun 15 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Beaulaurier, J., Zhang, X. S., Zhu, S., Sebra, R., Rosenbluh, C., Deikus, G., Shen, N., Munera, D., Waldor, M. K., Chess, A., Blaser, M. J., Schadt, E. E., & Fang, G. (2015). Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes. Nature communications, 6, [7438]. https://doi.org/10.1038/ncomms8438