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Bioengineering Seminar Series

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"Multiscale Patient-specific Systems Biology"

Scott L. Diamond, Ph.D.
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.  Hundreds of spatiotemporal reactions proceed within activating platelets and the polymerizing plasma when blood clots under flow.  Clinically, excessive bleeding and clotting represent the two extremes of blood function that often concern patients and their doctors. Using high throughput experimentation, they 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 (as measured using microfluidics), essential to prioritizing patient-specific cardiovascular risk and drug response or to identify unsuspected gene mutations.

Status

  • Workflow Status:Published
  • Created By:Karen Ethier
  • Created:05/15/2015
  • Modified By:Fletcher Moore
  • Modified:04/13/2017