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Sunday, August 11 • 11:00am - 12:00pm
BioKDD: Keynote talk : Eric Schadt

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The causal chain of events that lead to the development of complex diseases such as schizophrenia remains elusive. Such diseases are complex, resulting from the interplay of potentially hundreds (or thousands) of genetic loci and environmental factors. Genetic and environmental perturbations induce changes in the molecular interactions of cellular pathways whose collective effect may become clear through the organized structure of multiscale biological networks. We have developed a novel systems approach to study psychiatric disorders such as schizophrenia that models the global molecular, functional, and structural changes in the affected brain that in turn can lead us to the root causes of the disease. To characterize the molecular, cellular, and physiological systems associated with common human diseases, we constructed gene regulatory networks, functional and structural MRI based networks, high-content phenotypic networks and then integrated these network models across all of the data modalities generated across multiple human cohorts comprised of several thousand individuals. Because DNA variation was systematically assessed across all cohorts, it provides a common set of perturbations that can be leveraged to not only infer causal relationships among different molecular and higher order traits, but that can help link networks at different scales (e.g., molecular and imaging) across cohorts. Through this integrative network-based approach, we rank-order the resulting network structures for relevance to different diseases, highlighting both known and novel biological pathways involved in disease pathogenesis and progression. We demonstrate that the causal network structures we construct from this big data integration exercise is a useful predictor of response to gene perturbations and presents a novel framework to test models of disease mechanisms underlying disease. We further demonstrate that our approach can offer novel insights for drug discovery programs aimed at treating disease by screening our disease-associated networks against molecular signatures induced by marketed and novel compounds across a number of cell-bases systems, including those derived from stem cells isolated from patients with disease.

Sunday August 11, 2013 11:00am - 12:00pm CDT

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