Whether it is limiting an outbreak of food-borne illness caused by Salmonella or treating a serious communicable disease like tuberculosis, early detection is critical to success: the sooner officials know what they're dealing with and where it came from, the sooner they can take effective action to protect Canadians' health.
With the support of funding from the federal Genomics Research and Development Initiative (GRDI), Government of Canada scientists continue to build on discoveries made possible by past GRDI investments—developing innovative, genomics-based tools that are making the identification and tracking of infections more accurate, less costly, and faster than ever before.
At the Public Health Agency of Canada (PHAC), for example, GRDI funding enabled the research that led to the development of a fast and accurate genomics-based method for typing Salmonella. A subsequent GRDI investment led to SISTR—an interactive database of the genetic sequences of the more than 2,600 known types of the Salmonella bacteria.
The SISTR website is accessed virtually every day by researchers and public health authorities around the world, taking advantage of its ability to identify the type of Salmonella they're working on in a matter of minutes.
The trouble with Salmonella
While SISTR enables rapid typing of Salmonella—which sickens tens-of-thousands of Canadians a year—its ability to subtype the bacteria is limited. That's important because, even though only a few of the hundreds of types of Salmonella are common enough to be a real concern, each of those has hundreds of subtypes that are so similar, it's extremely difficult and time-consuming to tell them apart, even using DNA technologies.
"That's crucial information," says Dr. John Nash—Chief of Innovation and Application Development at the PHAC's National Microbiology Laboratory location in Guelph, Ontario. "Knowing which subtype is causing the illness is essential to tracking the source."
Taking out a few snips
The GRDI funded another research project at PHAC that addressed the issue. Out of the 4.5 million nucleotide pairs that make up Salmonella DNA, a team led by Dr. Roger Johnson identified 14 single nucleotide polymorphisms—SNPs, or just "snips"—where it appeared the genomes of subtypes would always differ.
"Roger's team developed a chemical approach to highlight these specific SNPs in the Salmonella DNA, demonstrating a more reliable way to identify a subtype, at less cost and in much less time—5 hours instead of 24."
To the next level
Now, a new GRDI investment has enabled a team at PHAC to capitalize on Dr. Johnson's discoveries— developing a test that automates subtyping, just as SISTR automates typing of Salmonella. Team leader Dr. Geneviève Labbé says the first job was to make the test as foolproof as possible. "To accomplish that, we took advantage of advances in sequencing technologies to identify hundreds of additional SNPs where subtypes most often differ from one another," says Dr. Labbé.
Next, the team applied the expertise in bioinformatics developed through earlier GRDI investments—in IRIDA, for example—developing a computer algorithm that picks the appropriate SNPs out of the millions of bits of data in Salmonella DNA, compares them to the SNPs of all the other Salmonella subtypes in the database, and delivers the result—all in a matter of seconds.
Fast, and flexible
Called BioHansel, this new tool promises to support enhanced surveillance, source attribution and risk assessment for Salmonella using fast subtyping—but there's more than speed.
As Dr. Labbé explains, BioHansel has other significant advantages: "Flexibility is a big one," says Dr. Labbé. "Just as the concept behind SISTR can be applied to type other pathogens such as E. coli, the algorithm BioHansel uses to identify SNPs can be adapted to subtype a whole range of pathogens that—until now—were thought to be too similar to tell apart."
Biologist Catherine Yoshida—who played a key role in the development of SISTR and now works with tuberculosis—can attest to BioHansel's flexibility. At the PHAC National Reference Centre for Mycobacteriology (NRCM) in Winnipeg, Mrs. Yoshida's team has replaced much of their traditional testing with whole genome sequencing (WGS).
Tuberculosis—TB—is the 10th leading cause of death in the world. It infects millions of people every year, including hundreds in Canada—and can be caused by a number of very closely related species of bacteria. "BioHansel has been key to enabling us to adopt WGS-based based testing," says Mrs. Yoshida, "Allowing us to determine which species—or strains—of the Mycobacterium tuberculosis complex are infecting people with a resolution that we've never had before."
More, and more to come
NRCM Biologist Daniel Kein—who was instrumental in adapting BioHansel for use with TB and continues to explore its potential to do more—notes that the new tool also allows researchers to see if a patient is infected with more than one strain of TB. "That's something that's been fairly difficult for us to see with our previous testing," says Mr. Kein. "Knowing whether a person is infected with more than one strain has important implications for epidemiologists, and maybe even drug resistance testing."
User friendly and ready to share
Another important advantage of BioHansel is its simplicity. "Unlike a lot of these kinds of tools, you don't need special training or high-powered computers to run it," says Mrs. Yoshida. "That's important, because if people can't or won't use it because it's too complicated or too expensive, Canadians won't get the benefit of its capabilities."
And for Mrs. Yoshida, that's perhaps the most important thing: "BioHansel is free, easy to run, and we're looking forward to sharing it with our provincial partners."