The future of discovery in the world of research goes beyond the walls of core teams. Collaboration across institutions, countries, and around the world will answer the biggest questions in years to come.
Over the last decade, the Applied Genomics team at Duke’s Center for Applied Genomics & Precision Medicine (CAGPM) has been trying to understand how the human immune system reacts to different kinds of infections. Ephraim Tsalik, MD, PhD, Micah McClain, MD, PhD, and Chris Woods, MD, are key investigators in CAGPM’s applied genomics program. Previously, much of their work has focused on infections at a high level – comparing virus to fungus or bacteria. With the emergence of COVID-19, researchers have learned that viruses don’t infect humans all the same way as it relates to their response. Some present with very mild symptoms, if any, while others require hospital care. CAGPM’s infectious diseases investigators are asking – why is that?
Tsalik, McClain, and Woods, along with other CAGPM team members, Geoff Ginsburg, MD, PhD, center director, Ricardo Henao, PhD, assistant professor in biostatistics & bioinformatics, Tom Burke, PhD, director of technology advancement and diagnostics, and Emily Ko, MD, assistant professor of medicine, recently co-authored a new publication in Frontiers in Immunology, “The Host Response to Viral Infectious Reveals Common and Virus-Specific Signatures in the Peripheral Blood.”
The collaboration, led by a colleague of Dr. Tsalik, Klaus Schughart, PhD, who is based in Germany, is finding key answers to how different viruses can be identified. Dr. Schughart has studied the immunological response to viral infections largely in animal models but recently received funding from his institution in Germany to expand to human patients.
The research team, also including Dr. L. Gayani Tillekeratne, who is an assistant professor in the division of infectious diseases and assistant research professor at Duke’s Global Health Institute, expanded the study to reach southeast Asia. Tillekeratne is co-director of the Ruhuna-Duke Centre for Infectious Diseases in Sri Lanka. In research, colleagues near and far are what will drive success in studies and multi-disciplinary teams are the future of driving discovery.
The study’s goal was two-fold – first, identify the shared aspects of the immune response to any virus, then further, identify the unique elements that might exist in response to any of the viruses in this study.
The team measured the human immune response by looking at the changes in gene expression. The lens of the study focused on which genes were active and which were repressed.
Enter Dr. Tom Burke and the Duke Center for Applied Genomics & Precision Medicine Biobank. Burke and his team oversee an impressive repository of over 340,000 high-quality, well-annotated biospecimens from well over 10,000 research participants enrolled in clinical genomic studies. This powerhouse team provides extensive research collaboration opportunities to leverage sequencing data.
“This study includes data derived from samples banked throughout nearly a decade, collected from four institutions on two continents,” said Burke. “This truly illustrates the value that Duke CAGPM provides as it relates to access of high quality and diverse biospecimen repositories from exquisitely phenotyped clinical research participants.”
Burke’s team helps to identify patients that may have been enrolled years ago that would be suitable for studies such as this one. The team will convert the samples into data and then engage the CAGPM statistical team, led by Ricardo Henao, PhD. Henao develops methodologies to analyze data and helps the team of investigators understand exactly what is going on in the patient’s biology.
The study found that there were unique elements to viruses, so where do we go from here?
“This study helps expand our biological understanding of these infections. We can also develop a test that measures this universal response to any viral infection,” said Dr. Tsalik. “You can imagine that with future new and emerging viruses, months before any test can be develop, we can at least determine whether the patient is responding to a viral pathogen, which can be critical to an effective public health response.”
The potential for future tests will add another layer of diagnostic testing and compliment current tests. Future tests could have the potential to measure biomarkers that are specific for viruses such as, influenza, coronavirus, and rhinovirus.
The Center for Applied Genomics & Precision Medicine is highly interdisciplinary and thrives as a hub to continue its discovery and development of analytic and translational approaches to diagnostic and biological insights into human diseases.