Building, Analyzing and Calibrating Multi-Scale Models in 2D and 3D: Tuberculosis as a Case Study

Denise Kirschner (April 17, 2019)

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Abstract

Multi-scale models (MSM) are increasingly being used to study complex biological processes. Multi-scale models span a range of both spatial and temporal scales and can also encompass multiple physiological compartments. MSMs are growing more complex and cumbersome and it is necessary to coarse grain model aspects when appropriate. A new approach that we call tuneable resolution can provide that flexibility. Additionally, analyses of MSMs can be difficult, and we have fine-tuned a global uncertainty and sensitivity analysis approach that can be applied to all MSM types performing both inter- and intra-scale analyses and to assist with model calibration and validation. Finally, we have been exploring optimization, for example of drug treatment regimens, in the context of MSMs and have identified protocols that are computationally efficient. We will explore all of these topics in the context of our extensive work in the area of the host immune-response to infection with the bacterium Mycobacterium tuberculosis.