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Philippine Researchers Aim to Sequence Dengue Virus, Anthrax, Plague, and Undiagnosed Diseases


By Monica Heger

With a new Roche 454 GS Junior, researchers at St. Luke's Medical Center in the Philippines will begin characterizing the genetic diversity of viral and bacterial pathogens of the Philippines as well as sequence banked clinical samples from patients with mysterious diseases.

The sequencing effort has two aims: to characterize genetic diversity of pathogens and to eventually develop better diagnostics and treatments for viral and bacterial strains that are specific to the Philippines.

The project is especially needed because samples cannot be exported from the Philippines, so it is difficult to ensure that current treatments for dengue, say, will be effective against specific isolates from the Philippines, said Evan Skowronski, the chief scientific officer at the Tahoe Research Institute, which funded the purchase of the GS Junior.

The incidence of dengue in the Philippines has increased dramatically in recent years, with more than 100,000 cases reported in 2010, a 140 percent increase over the previous year.

St. Luke's has just begun sequencing a patient sample infected with Yersinia enterocolitica, a close relative of Y. pestis, the bacteria that causes plague, and a major cause of morbidity in the Philippines, said Skowronski.

The St. Luke's team also has thousands of samples of dengue, and sequencing of those is "just getting of the ground." Aside from dengue, the team aims to sequence other related viruses and other pathogens of interest, such as Y. pestis and Bacillus anthracis. The goal is to sequence 100 isolates this year.

The team would like to sequence an isolate from a huge plague outbreak that occurred in the 1950s, as well as clinical isolates of B. anthracis, which have caused a number of deaths due to eating beef from infected cows.

Sequencing strains in the Philippines will allow researchers to determine differences between viral strains in the Philippines and elsewhere, pinpointing how the virus has evolved and identifying potential mechanisms of resistance, all of which will eventually enable better diagnostics and therapeutics.

"There are a lot of confirmed [dengue] cases that don't type by serology methods," said Skowronski. Additionally, while vaccines are under development, they are not based on isolates from the Philippines, so "we have no idea whether the assays work or not," he added.

Aside from the sequencing of dengue, anthrax, and the plague bacteria, researchers at St. Luke's are aiming to sequence clinical samples from patients with diseases that were never diagnosed.

Sequencing is an ideal tool, said Skowronski, because "if you can get a clean clinical sample and sequence it, you can pick the 5, 10, or 20 reads out of thousands that are the signature of a novel virus."

That can be done relatively quickly compared to the current paradigm, in which it can take months if not years after an outbreak for a paper that identifies the novel virus to be published, said Skowronski.

The idea of using next-gen sequencing as a public health tool to monitor disease outbreaks is gaining traction as a viable option within the research community.

Researchers in Canada recently used sequencing to uncover the cause of a tuberculosis outbreak (IS 3/1/2011), and last year, scientists at Pacific Biosciences used sequencing to identify the origin of the cholera outbreak in Haiti (IS 12/14/2010).

Have topics you'd like to see covered by Clinical Sequencing News? Contact the editor at mheger [at] genomeweb [.] com.

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