Whole Genome Sequencing: Redefining the Landscape of Public Health Microbiology

PHILADELPHIA, PA—“Whole genome sequencing is completely redefining the landscape of public health microbiology. These advances, which can define the complete genetic makeup of microorganisms, are opening a new era for controlling infectious threats.”

That’s the conclusion of Beth P. Bell, MD, MPH, Director of the National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention, Atlanta, GA, who presented one of the closing plenary lectures at IDWeek 2014.

Dr. Bell focused on the public health benefits of next generation diagnostic testing. These include more rapid and precise diagnosis with point of care and culture-independent tests, earlier outbreak detection, and improvements in antibiotic use.

An average bacterial pathogen has 3–5 million nucleotides. “Ten years ago, it would take several months and thousands of dollars to sequence a single bacterial genome,” with 50,000 nucleotides a day sequenced with the fastest instruments.

“Today, we can sequence dozens of genomes a day,” she said. “By using whole genome sequencing, we find ourselves on the verge of a revolutionary change in our ability to diagnose infectious diseases, to investigate and control outbreaks, to understand transmission patterns, to develop and target vaccines, and to determine antimicrobial resistance.”

Dr. Bell presented several examples of how the CDC is using whole genome sequencing.

The first is for national listeriosis surveillance, for which a pilot project was initiated in September 2013. The goal: near “real-time”’ sequencing and analysis of isolates from all U.S. clinical cases of Listeria monocytogenes infection as well as those from food-environmental sources, with the sequencing completed within 1 week of receipt of the isolate. This would help “improve the resolution and timeliness of cluster identification and epidemiologic follow-up,” she said.

The second is early identification of influenza mutations to monitor emerging changes in viral populations, which can be useful in designing vaccines.

The third is characterizing chains of transmission of the hepatitis B virus, which can help understand emerging outbreaks.

Finally, MERS-CoV genome sequencing will assist in accelerating outbreak responses.

“Whole genome sequencing and other high thorough technologies really do hold the promise of enormous public health benefits, but there are a lot of challenges in terms of data transmission, management, analysis, storage, integration, security, implementation and maintaining capacity, and addressing the issue of moving away from reliance on cultures,” Dr. Bell said.

This includes lack of standardization; data volume, rate, and complexity, with the technologies representing an increase of more than 100,000 times in terms of raw data output; limited reference data; and need for specialized systems and expertise: bioinformatics and data science are new disciplines for public health.

The CDC is just beginning the second year of a 5-year Advanced Molecular Detection initiative, which combines epidemiology, next generation sequencing, and bioinformatics. The goals are to improve pathogen identification and detection; adapt new diagnostics to meet evolving public health needs; help states meet future reference testing needs in a coordinated manner; develop prediction, modeling, and early recognition tools; and develop consensus standards, databases, and analytical approaches.

Collaboration and partnerships will be crucial to navigating this transition and leveraging the next generation of tools and methods.

“I think it’s fair to say that we in public health are just beginning to learn how we can benefit from the sorts of advances that we’ve been seeing in the clinical sector,” Dr. Bell said.