Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Neuromuscular disorders (NMDs) are a large group of diseases that affect the nerves and muscles and are caused by changes in more than 600 different genes. Patients with NMDs have a wide range of symptoms, including muscle weakness, respiratory failure, and fatigue. Despite advances in genetic testing, 30-50% of children with NMDs still lack a genetic diagnosis due to limitations in current methods for interpreting genetic changes (variants). Without a genetic diagnosis, these children cannot receive appropriate care. New computational and artificial intelligence (AI) approaches can help to solve these most challenging unsolved cases, but a detailed understanding of the disease and experimental validation is still required. We aim to analyze the genetic changes in the genomes of affected individuals using cutting-edge AI and data science methods to provide a genetic diagnosis and understand how the genetic changes cause the disease. We will analyze genome data from 500 patients with unsolved NMD using innovative tools and network analysis methods. We will develop a computational workflow using AI tools and combine this with biological knowledge to better understand whether the variant(s) in the child's genome could be responsible for their disease. We will then validate our gene/variant of interest using animal or cell models and functional experiments in our lab and with the help of our global collaborations. Our results will help provide genetic diagnoses to children, potentially identify new disease-causing genes, and reveal novel mechanisms of disease. This will enable children to receive appropriate treatments and participate in clinical trials.