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"Multiscale Patient-Specific Systems Biology"
Scott L. Diamond, PhD
Professor and Chair, Department of Chemical and Biomolecular Engineering
Institute for Medicine and Engineering
University of Pennsylvania
Predicting tissue function based upon an individual’s unique cells requires a multiscale
Systems Biology approach to understand the coupling of intracellular signaling with
spatiotemporal gradients of extracellular biochemicals. In the cardiovasculature, extracellular
species are also controlled by convective-diffusive transport. Using high throughput
experimentation, we obtained a large set of platelet responses to combinatorial activators in
order to train a neural network (NN) model of platelet activation for several individuals. Each
NN model was then embedded into a kinetic Monte Carlo/finite element/lattice Boltzmann
simulation of stochastic platelet deposition under flow. In silico representations of an
individual’s platelet phenotype allowed prediction of blood function under flow, essential to
prioritizing patient-specific cardiovascular risk and drug response or to identify unsuspected
gene mutations.
Chatterjee MS, et al. Nature Biotechnology 28:727 (2010)
Flamm MH, et al. Blood 120:190 (2012)