Integrating exome sequencing, mRNA-seq, and microRNA-seq to identify genes and mechanisms in optic nerve degeneration
In glaucoma, progressive optic nerve degeneration can lead to irreversible vision impairment and eventual blindness, despite treatment. Genetic causes and influences are not yet clear in primary open angle glaucoma (POAG), the most prevalent form of the disease in North America, Europe, and several other parts of the world. The genetics of POAG are complex; to date, no single causative genomic variant has been established as causing the disease.
Genome-wide sequencing of exons from protein coding and non-coding genes in 333 patients with primary open angle glaucoma revealed over 100 associated SNP sites in over 70 genes. To rank and prioritize genes and generate hypotheses about molecular mechanisms disrupted by associated variant sites, mRNA and small RNA (microRNA) were sequenced from ocular tissues relevant to the disease.
My computer science research interests center on logic-based methods for answering queries about large bodies of diverse distributed knowledge. I use semantic information, that is, data about the data, to develop alternative, or cooperative, answers to queries. In the years since my Ph.D., I have been exploring problems in computational molecular biology using logic programming techniques in general and cooperative answering strategies in particular. In collaboration with genome sequencing groups in Canada, the U.S., and Europe I have built a system called MAGPIE (Multipurpose Automated Genome Project Investigation Environment) for analyzing DNA sequence data in real-time during and beyond the lifetime of a sequencing project.