July 22, 2013  |  Microbial sequencing methods

Whole-Genome Microbial Epigenetics: ASM Workshop videos highlight emerging application of SMRT Sequencing

We recently participated in a workshop on whole-genome microbial epigenetics at the American Society for Microbiology annual meeting in Denver. Using SMRT® Sequencing, the three most common types of bacterial methylation can be studied at base resolution across an entire genome. An exceptional lineup of speakers shared their latest research and we’re pleased to be able to share video of the presentations.

Our CSO Jonas Korlach opened the workshop with a brief introduction describing how SMRT Sequencing generates epigenetic information. His presentation was followed by Brian Anton, from New England BioLabs, who presented data on restriction-modification systems and orphan methylases analyzed with SMRT Sequencing. Anton noted that twice as many methyltransferase (MTase) recognition motifs had been decoded in the past two years on the PacBio® system as had been discovered in the previous forty years of research! He also included a phylogenetic analysis of MTase genes and reported that most DNA MTases appear to be gained or lost at a rapid evolutionary rate via horizontal gene transfer.  Watch video: Large-Scale
Analysis of Restriction-Modification in Systems Using SMRT Sequencing

As scientists find particular MTases and modification events for the first time, they are appreciating a previously unknown complexity in microbial epigenetics. Sebastian Suerbaum from Hannover Medical School reported on the methylome analysis between two strains of the bacteria Helicobacter pylori, finding that genome-wide methylation patterns are highly complex and divergent. The study revealed 32 methylated motifs, with just seven shared in both strains; of the 32 total motifs, 11 were completely new findings.

Bart Weimer from the University of California, Davis, shared data from the 100K Pathogen Genome Project. He noted that the food preparation process serves as an ideal environment in which microbes’ genomes may rapidly evolve and rearrange; this contributes to the high diversity of serotypes of some of these pathogens. Closed genomes and whole-genome methylation data from SMRT Sequencing have enabled Weimer and his team to produce a more accurate phylogenetic tree of serotypes; skip the culturing step to get results faster; and discover new epigenetic modifications in Salmonella and Listeria. Watch video: Genomics in Food Security – 100k Pathogen Genome Project

On a similar note, Peter Evans from the US FDA reported on whole-genome sequencing and methylome analysis for several bacteria relevant to public health. He said that having the comprehensive view of each microbe was critical, especially in cases where it is important to tell the difference between an outbreak case and sporadic illness, or to trace the source of an outbreak. Evans also compared sequencing data across the PacBio, 454®, and MiSeq® platforms. Watch video: Epigenetic Analysis of Salmonella and other Bacteria of Public Health Importance

In another presentation, Greg Harhay from the USDA Meat Animal Research Center (USMARC) offered data on pathogens involved in bovine respiratory disease complex, which costs the livestock industry more than $1 billion annually and is the single biggest reason for the use of antibiotics in cattle. Harhay’s team used the PacBio system to analyze several isolates from two different pathogens, assembling their genomes and elucidating their methylation patterns. Watch video: The Methylome and Virulence of Bovine Respiratory Disease Bacterial Pathogens

Garth Ehrlich, from Allegheny Singer Research Institute, reported on new studies of pneumococcal epigenetics. Streptococcus pneumonia, which causes more than 1.6 million deaths annually, has a highly plastic genome and more than 90 serotypes. Methylation analysis with SMRT Sequencing found a potential novel T modification in addition to the expected epigenetic changes.  Watch video: Studying Whole-Genome Pheumococcal Epigenetics

The final presentation came from epigenetics expert Michael Jennings from Griffith University, who defined the phasevarion, or the phase variable regulon mechanism in host-adapted pathogens. Jennings explained the mechanism, mediated by methyltransferases, which switches expression of multiple genes on or off in a coordinated fashion and has significant implications on pathogen virulence. He noted that recent studies of whole methylomes in wild-type versus knockout strains have allowed his team to rapidly identify methylation targets and to correlate this phenomenon to promoter activity. Watch video: Studying Whole-Genome Pheumococcal Epigenetics – Phasevarions: Phase Variation of Type III DNA Methyltransferases Controls Coordinated Switching in Multiple Genes

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