First-of-a-kind web tool for exploring splicing misregulation in human disease (2011)




The human genome can be thought of as a computer program that controls the generation of biological complexity and the activities within living cells. While the text comprising the genome was revealed 10 years ago when the genome was ‘sequenced’, deciphering the genetic code hidden within the genome has been difficult. Recently, Drs. Brendan Frey and Benjamin J. Blencowe at the University of Toronto have developed a method that enabled them to identify the instructions comprising a ‘splicing code’ within the genome (Barash et al, Nature 2010 Website for Alternative Splicing Prediction). In this pilot project, they examined the potential for using the splicing code to enable biomedical research. They re-oriented their analysis toward the causes of human disease, invented a methodology for predicting the effects of genetic mutations, and developed a prototype web tool that demonstrates how the tool can be used to enable medical research. This pilot project was successful and led to 1) the development of a $1 million proposal to scale up the approach to fully support medical research, 2) a collaboration between the University of Toronto, Cold Spring Harbor to investigate the causes and therapeutic treatment of spinal muscular atrophy, the leading cause of infant mortality, and 3) the training of graduate students and postdoctoral fellows who are now working to scale up the methodology to support medical research. The exploratory research enabled by this project has opened the door to a new major direction of research in the Canadian genomics community.