Next-generation sequencing (NGS) is the automation of high-throughput DNA sequencing on a massive scale that is rapidly transforming biology and medicine. It can enable laboratories to detect small, but clinically significant, numbers of drug-resistant viruses in blood samples from infected individuals.
The lack of computational tools to process and interpret NGS data collected from rapidly-evolving populations such as HIV remains a major obstacle in the application of NGS to HIV treatment and prevention. Dr. Poon’s research will bridge this divide by developing computational methods for NGS analysis designed to address key issues in HIV prevention and treatment. He will share his software as a free resource to the basic and clinical research communities.
He will take advantage of resources available to him through the BC Centre for Excellence in HIV/AIDS (BC-CfE): an extensive archive of HIV plasma specimens; one of the world’s few NGS cores dedicated to HIV research; and his own expertise in molecular evolution and bioinformatic sequence analysis.
As part of his research, he is developing and validating a new method to reconstruct the time of HIV infection from NGS data. Using specimens from the BC-CfE, he will estimate times of HIV infection and reconstruct the historical trend of HIV incidence (the rate of new HIV infections) in BC. This will help assess the long-term impact of expanding access to HIV therapy in BC and identify other correlates of HIV incidence.
He will also use “phylogenetic” methods, which can infer the ancestral tree that relates observed genetic sequences, to reconstruct the history of HIV transmissions in BC. This will allow him to evaluate the impact of expanding access to HIV therapy in BC on the rate of transmitting drug-resistant HIV, and to characterize the variation in rates of HIV transmission over the course of the epidemic.
Finally, he will develop a new class of methods for analyzing NGS data to characterize the adaptation of HIV to the host-specific immune response, and to reconstruct the genetic sequence of the transmitted HIV strain. The results from these methods can provide key information for the development of HIV vaccine candidates – a core aim of HIV prevention research.