Dr. Stephen Bentley, Senior Staff Scientist at the Wellcome Trust’s Sanger Institute, Cambridge, United Kingdom, gave a seminar entitled “Whole genome sequencing for high resolution genotyping of bacterial populations” at the Virginia Bioinformatics Institute (VBI) Conference Center on Monday, June 14.

Bentley described how new sequencing technologies are changing the scale and types of clinical studies possible for bacterial organisms. The availability of next generation sequencing technologies has caused a dramatic shift in the type of projects that can be tackled. Significant opportunities are opening up in areas that include disease surveillance/epidemiology, the origin and cause of disease, gene expression analysis of bacterial isolates, as well as metagenomic studies.

In his talk, Bentley described the use of next generation sequencing technologies to study genetic diversity in Staphylococcus aureus and Streptococcus pneumoniae, two projects where the analysis of multiple samples in parallel on next generation sequencing platforms (multiplexing) was delivering results. For S. aureus and S. pneumoniae, antibiotic resistance is a big problem worldwide. High-resolution genotyping of both bugs is shedding light on:

  • The multiple independent acquisition of antibiotic resistance
  • The acquisition and global distribution of different disease-related genetic elements
  • Patterns of genetic recombination amongst genomes
  • Dates of emergence of antibiotic-resistant bacterial strains
  • Serotype switching (vaccine development)

Work in Bentley's laboratory had helped to build a picture of the evolution of antibiotic-resistant S. aureus transmission that has resulted from hospital treatments and how such infections have spread across the globe. Large-scale sequencing data can be used to rapidly build robust phylogenetic trees where details of outbreaks and likely transmission routes were evident. For the group's work on Streptococcus pneumoniae, a significant challenge was posed by the extent of genomic recombination that this organism undergoes. It was important to detect and adjust for recombination in the experimental approach to build a robust phylogenetic tree. Beyond the low hanging fruit, Bentley emphasized the importance of metadata to enhance the amount of useful information that could be gleaned from the deluge of sequence data.

What does the future look like? Visualization of large data sets will become increasingly important. Research is underway, for example, to link phylogenetic trees with Google maps in a user-friendly interface. Bentley's group has been working on Artemis (www.sanger.ac.uk/resources/software/artemis), a DNA sequence visualization and annotation tool that is particularly suited to analyze the compact genomes of bacteria, archaea, and lower eukaryotes.

Third generation technologies mean that the landscape is going to change in a big way sometime soon. Companies with innovative technologies are targeting clinical applications that have significant potential for rapid diagnostics. What takes a week on some of the platforms available today is likely to take a couple of hours using the next wave of technologies. This will be possible due to even longer reads of DNA sequence and reduced sampling handling times.

Published by Public Relations, June 21, 2010