Title: Cardiac Systems Biology and Multi-Scale Modeling

Abstract: Computational models of the heart can be integrative in several important ways. First, they permit information integration of genome scale data sets that would otherwise be difficult to interpret and understand. We illustrate this in the analysis of high-throughput phenotypic and metabonomic data on cardiac function in the fruitfly drosophila melanogaster. We use drosophila as a model organism for studying cardiac aging and hypoxia tolerance, and integrating these data with genome-scale metabolic models. Systems models of cardiac myocytes achieve functional integration, by predicting how the functions of individual network components combine to give rise to physiological functions. We illustrate this with our recent models of b-adrenergic regulation of myocyte excitation-contraction coupling. Multi-scale computational models aim to achieve structural integration across physical scales of biomedical organization from molecule to organize. We illustrate this with examples from our recent research on arrhythmia mechanisms in genetic disease and the effects of external interventions such as pacing and pericardiectomy on ventricular-vascular coupling in vivo.

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