Brett Trost, Molecular Genetics

Supervisor 
Stephen Scherer, Senior Scientist, Genetics and Genome Biology, Hospital for Sick Children and University Professor, Department of Molecular Genetics, University of Toronto.

Thesis
Dr. Trost’s PhD thesis, “Design and Data Analysis of Kinome Microarrays”, describes computational methods that facilitate the creation and use of kinome microarrays, a technology for studying how cells communicate. Specifically, his thesis describes two novel algorithms, called DAPPLE and PHOSFER, for designing kinome microarrays, as well as a new statistical method, PIIKA, for accurately analyzing data from these arrays. DAPPLE, PHOSFER, and PIIKA have been used by the United States National Institutes of Health to study the Ebola, Pichinde, and monkeypox viruses, with the results suggesting potential treatments for these infections. They have also been applied to numerous other problems in human health (breast cancer; medulloblastoma; cystic fibrosis; arthritis) and agriculture (colony collapse disorder in honeybees; Johne's disease in cattle; fungus infection in soybeans; and Salmonella infection in chickens). All three methods are freely available on the internet and have collectively been used thousands of times by hundreds of unique users. Dr. Trost received several prestigious awards for his thesis work, including the University of Saskatchewan PhD Thesis Award and the Governor-General’s Academic Gold Medal.

Dr. Trost’s postdoctoral research has focused on the detection and interpretation of genetic variants associated with human disease. The first study led by Dr. Trost during his postdoctoral fellowship developed a workflow for accurately detecting copy number variants (large deletions or duplications of genetic material) from human whole-genome sequencing data. Published in the American Journal of Human Genetics, this workflow has recently been used to identify pathogenic genetic variants in more than 20,000 individuals with autism and their family members. In addition, Dr. Trost’s workflow is now a standard component of the genomic analysis pipeline used by The Centre for Applied Genomics, Canada’s largest DNA sequencing centre, where it is applied to thousands of genomic samples every year. Dr. Trost has also been involved in a wide range of other exciting projects during his postdoctoral fellowship, including the sequencing of the Canadian beaver genome; an evaluation of blood, saliva, and cheek-swab samples for DNA sequencing; the whole-genome sequencing of healthy individuals as part of Canada’s Personal Genome Project; and studies providing insight into the genetics of heart disease, Huntington’s disease, and metabolic disorders.

Previously, tandem repeat expansions have been associated with many diseases, most famously Huntington’s disease, but they had never before been associated with a disorder with complex genetics like autism. In a study published last year in Nature, Dr. Trost working under study-lead Dr. Ryan Yuen (Assistant Professor in the Department of Molecular Genetics), showed that tandem repeat expansions may account for up to 2.6% of autism cases, opening the door to many avenues of further research, both in autism and in other diseases with complex genetics.

Dr. Trost has received numerous prestigious awards during his postdoctoral fellowship, including the Hospital for Sick Children Lap-Chee Tsui Fellowship for Research Excellence, the Canadian Open Neuroscience Platform Research Scholar Award, and the CIHR Banting Postdoctoral Fellowship, for which ranked in the top 2% of applicants across Canada. He was also one of approximately 600 young scientists worldwide selected to attend the 2018 Lindau Nobel Laureate Meeting, which was attended by nearly 40 Nobel Laureates.

Although genome sequencing is becoming more and more widespread, the function and regulation of the human genome remain poorly understood. Upon completion of his postdoctoral fellowship, Dr. Trost plans to start his own laboratory dedicated to using computational and statistical methods for advancing our understanding of the genetics of human disease.