Coarse Graining data-driven cellular models in multiscale ... · PDF fileCoarse Graining...
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Coarse Graining data-driven cellular models in multiscale simulations
Scott L. Diamond, PhD
Director, Penn Center for Molecular DiscoveryInstitute for Medicine and Engineering
Departments of Chemical & Biomolecular Engineering and Bioengineering
University of Pennsylvania Philadelphia PA 19104
www.seas.upenn.edu/~diamond
www.BloodSystemsBiology.org
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Blood Systems Biology
Topology interaction networks - nodes and linkages
reaction type
Parameterskinetic constants kiinitial conditions ci (0)
Predictions: System evolution Ci (x,y,z,t)
Numerics:CFD/LBNN/ODE
LKMC/PDE
Physicsdiffusion velocity pressurebond strengthsVWF mechanicsgeometryC. Taylor Lab (Stanford)
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Signaling pathways converging on calcium mobilization
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Signaling pathways converging on calcium mobilization
Purvis, et al. Blood 2008Purvis, et al. PLoS Comp Biol. 2009Dolan & Diamond, Biophys. J. 2014
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Pairwise Agonist Scanning (PAS)
Chatterjee, et al. Nature Biotechnology 2010
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Sequential and ternary addition of: SFFRN, CVX, ADP
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Flamm et al. J. Chem. Phys. 2009
Flamm et al. J. Chem. Phys. 2011
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Flamm et al. Blood, 2012
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Microfluidic phenotyping of individual subjects (PPACK-whole blood over collagen 200 s-1)
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Platelet function during thrombosis and hemostasis
αIIbβ3*
GP1b
vWF
GPVI
collagen collagen
α2β1*
ADPTXA2 thrombin5HT
laminin
α6β1*
flow
TF-VIIa XIIa
XaIXa
XIa
fibrin
contact activators:collagen,DNA, RNA
polyphosphateartificial surfaces
capture arrest activation
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Neural Network Architecture
Thrombin
Lee et. al., PLOS Computational Biology., 2015
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Neural Network Architecture
Lee et. al., PLOS Computational Biology., 2015
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Trinary Predictions
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Sequential Exposures ‐ Predictions
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Future work: Diagnostics – acute MI, trauma, hemophilia, neonatal, drug response
Patient-specific Acute MI:2D 3D calculations,Adaptive meshing, GPUsParallel processing