New genomic sequencing diagnostic tool targets reproductive failure in cattle herds

Bovine reproductive failure, which results in decreased fertility and pregnancy rates, is a major concern for livestock producers in beef and dairy sectors. In many cases, the exact disease-causing organisms responsible for reproductive issues in cattle are difficult to pinpoint, leaving producers struggling to find effective solutions. These problems can lead to significant financial losses due to reduced herd productivity.

“We see many of these cases each year at PDS, and they are challenging to diagnose because there are many reasons for abortions in cattle,” says Dr. Yanyun Huang (PhD), chief executive officer of PDS, the province’s veterinary diagnostic laboratory, and an adjunct professor in the WCVM’s Department of Veterinary Pathology.

Huang, the study’s principal investigator, developed its concept as a method of thorough diagnostic workup and to reduce costs per target pathogen for livestock producers.

“Lab detection is a key part of diagnosis. For example, farmers notice a problem in their herd and call their vet, who decides to test for one or two pathogens. Then they submit samples to the lab, and if they come back negative, they tell the lab to test for two different pathogens,” says Huang.

“Through this process, producers can spend a lot of money and time in delaying real results and cannot actually test for all of the things that are worth testing.”

In 2022, Huang received funding from the Saskatchewan Agriculture Development Fund (ADF) to develop BovReproSeq, a tool that uses next-generation sequencing (NGS) technology to analyze collected clinical samples for 17 bacterial, viral and protozoal pathogens known to cause infertility, abortions and stillbirths in cattle. The diagnostic speed and accuracy of BovReproSeq testing is an upgrade from traditional tests, which often require multiple rounds of separate testing for specific pathogens.

To develop this innovative technology, Huang partnered with Dr. Janet Hill (PhD), professor and head of the WCVM’s Department of Veterinary Microbiology, and Dhinesh Periyasamy, a Master of Science (MSc) student and PDS technical specialist.

“Dr. Huang and I have shared interests in addressing these types of issues, and we both knew that Dhinesh would be a really great fit to take on this study as part of his master’s program,” says Hill, Periyasamy’s graduate supervisor. “I love this part of my work because it’s collaborative and explores new experiences and opportunities.”

Periyasamy consulted with veterinarians and pathologists to determine the list of pathogens that should be included in BovReproSeq, then began the challenge of gathering samples and constructing the panel.

“Because this type of testing is a new approach to the issue, we couldn’t draw on previous studies to … streamline and standardize our method,” he says.

Periyasamy analyzed diagnostic results from clinical samples of bovine reproductive failure cases at PDS, which included positive clinical samples for each of the 17 pathogens to be targeted with BovReproSeq. Once collected, he compared the BovReproSeq results for 116 samples to results from traditional testing requested by veterinarians in previous cases.

“BovReproSeq produced a 99 per cent accuracy [rate] so that’s a very good outcome. We had 11 cases that produced false negatives and most of the false negative cases had very low pathogen loads, so we’ve identified some limitations in terms of analytical sensitivity,” Periyasamy says.

He notes that the promising development and validation testing of BovReproSeq was part of the first phase of the team’s findings, which were recently shared in a research paper published in the Journal of Clinical Microbiology.

In the study’s second phase, which is underway and funded by the Beef Cattle Research Council (BCRC), the researchers will test 100 additional diagnostic cases in real time and then compare replicated results to a panel of standard tests.

“This testing is much more comprehensive and includes toxicological testing. This is being utilized right now with our clients and we’re hopeful that by the end of 2025, we will release the product to be utilized by veterinarians,” says Periyasamy.

Huang says that early feedback from clients and veterinarians who use the testing has been positive, and he hopes BovReproSeq can gain traction and provide a lasting contribution to the livestock industry.

“We anticipate this will be the gold-standard for how producers and veterinarians approach testing with bovine reproductive failure. I’m very proud of how our team has worked together to make this project successful,” says Huang.

“These kinds of collaborations between the WCVM and PDS are so important to foster. It’s just one way we can complement each other’s strengths and address real word issues.”