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Moncrief Grand Challenge Faculty Awards - Inderjit Dhillon

Research Topic: “Disease Modeling Via Large-Scale Network Analysis”

Abstract: The ability to predict how changes in genotype affect phenotype would have wide applications, perhaps most importantly the rational identification of genes whose mutation predisposes an individual to a given disease. It remains extraordinarily difficult to identify causal genes in most genetic diseases, in particular highly polygenic disorders, such as cardiovascular disease, schizophrenia, diabetes, and majority of birth defects, for which current approaches are most limited. However, in recent years, there has been an enormous growth in the amount and variety of information that one can use in this endeavor. In the proposed research, we plan to develop a mathematical and data-driven approach to identify genes underlying a given trait or disease, with immediate applications to discover genes associated with highly polygenic diseases. The proposed research will develop mathematical models for relationships between genes and phenotypes. This will enable the development of novel mathematical techniques that derive their roots from areas as diverse as graph theory, network analysis, probabilistic graphical models and compressive sensing. Though the proposed research will be targeted towards finding associations between genes and diseases, the mathematical models and techniques developed are expected to advance the state of the art in diverse areas such as social network analysis, graphical models and matrix completion (compressive sensing), and will be accompanied by software packages for analyzing and visualizing such datasets.