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Integrated Mechanistic-Empirical Modeling of Cellular Response Based on Intracellular Signaling Dynamics

[+] Author Affiliations
Michaëlle N. Mayalu, H. Harry Asada

Massachusetts Institute of Technology, Cambridge, MA

Paper No. DSCC2013-3806, pp. V003T43A002; 5 pages
doi:10.1115/DSCC2013-3806
From:
  • ASME 2013 Dynamic Systems and Control Conference
  • Volume 3: Nonlinear Estimation and Control; Optimization and Optimal Control; Piezoelectric Actuation and Nanoscale Control; Robotics and Manipulators; Sensing; System Identification (Estimation for Automotive Applications, Modeling, Therapeutic Control in Bio-Systems); Variable Structure/Sliding-Mode Control; Vehicles and Human Robotics; Vehicle Dynamics and Control; Vehicle Path Planning and Collision Avoidance; Vibrational and Mechanical Systems; Wind Energy Systems and Control
  • Palo Alto, California, USA, October 21–23, 2013
  • Conference Sponsors: Dynamic Systems and Control Division
  • ISBN: 978-0-7918-5614-7
  • Copyright © 2013 by ASME

abstract

A hybrid modeling framework integrating a highly specific mechanistic model with highly abstract empirical model is presented. With the growing interest in the scientific and medical community for identification of therapeutic targets in treatment of disease, it is necessary to develop predictive models that can describe cellular behavior in response to environmental cues. Intracellular signaling pathways form complex networks that regulate cellular response in both health and disease. Mechanistic (or white-box) models of biochemical networks are often unable to explain comprehensive cellular response due to lack of knowledge and/or intractable complexity (especially in events distal from the cell membrane). Empirical (or black-box) models may provide a less than accurate representation of cellular response due to data deficiency and/or loss of mechanistic detail. In the proposed framework, we use a mechanistic model to capture early signaling events and apply the resulting generated internal signals (along with external inputs) to a downstream empirical sub-model. The key construct in the approach is the treatment of a cell’s biochemical network as an encoder that creates a functional internal representation of external environmental cues. The signals derived from this representation are then used to inform downstream behaviors. Using this idea, we are able to create a comprehensive framework that describes important mechanisms with sufficient detail, while representing complex or unknown mechanisms in a more abstract form. The model is verified using published biological data describing T-Cells in immune response.

Copyright © 2013 by ASME

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