Discovering molecular mechanisms of human disease through gene sets and networks
Molecular processes play a key role in the development of disease.
Yet, there is still not enough known about molecular causes of
disease. In this thesis, we introduce methods to discover hidden
connections between biological functions and disease using gene sets
We first investigate a topological property of pathways in protein-protein interaction networks. We find mediating pathways for three pulmonary diseases using a new measurement called pathway centrality which measures the amount of information flow between disease genes and differentially expressed genes handled by a pathway. Second, we identify connections between developmental processes and disease by statistically testing overlaps between developmental gene sets and disease gene sets. We handle missing disease-gene association information by pooling disease genes from specific disease terms to more general disease terms in a disease taxonomy. While successful, this work highlights a need for more molecular disease taxonomies to improve the efficacy of gene pooling. We therefore performed a pilot study to infer disease hierarchies only using disease-gene association information.
In this talk, I will talk about our methods that highlight novel connections between gene sets and disease, and our findings that may lead to development of new therapeutic solutions.