High-Performance Agent-Based Modeling Applied to Vocal Fold Inflammation and Repair

Abstract

Fast and accurate computational biology models offer the prospect of accelerating the development of personalized medicine. A tool capable of estimating treatment success can help prevent unnecessary and costly treatments and potential harmful side effects. A novel high-performance Agent-Based Model (ABM) was adopted to simulate and visualize multi-scale complex biological processes arising in vocal fold inflammation and repair. The computational scheme was designed to organize the 3D ABM sub-tasks to fully utilize the resources available on current heterogeneous platforms consisting of multi-core CPUs and many-core GPUs. Subtasks are further parallelized and convolution-based diffusion is used to enhance the performance of the ABM simulation. The scheme was implemented using a client-server protocol allowing the results of each iteration to be analyzed and visualized on the server (i.e., in-situ) while the simulation is running on the same server. The resulting simulation and visualization software enables users to interact with and steer the course of the simulation in real-time as needed. This high-resolution 3D ABM framework was used for a case study of surgical vocal fold injury and repair. The new framework is capable of completing the simulation, visualization and remote result delivery in under 7 s per iteration, where each iteration of the simulation represents 30 min in the real world. The case study model was simulated at the physiological scale of a human vocal fold. This simulation tracks 17 million biological cells as well as a total of 1.7 billion signaling chemical and structural protein data points. The visualization component processes and renders all simulated biological cells and 154 million signaling chemical data points. The proposed high-performance 3D ABM was verified through comparisons with empirical vocal fold data. Representative trends of biomarker predictions in surgically injured vocal folds were observed.

Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification

“…Cells would perform their actions as a function of the concentrations of chemokines and ECM on their current and nearby patches. A detailed description of VF-ABM can be found in [25]. The overview of the VF-ABM is illustrated in Algorithm 1.…”

Agent‐based models of inflammation in translational systems biology: A decade later

“…In addition to the ability to facilitate the development and use of increasingly sophisticated ABMs, there have also been methodological improvements for both improving ABMs as well as analyzing the output of simulation experiments utilizing them (Figure ). These developments include work on uncertainty quantification in ABMs (Marino, Hogue, Ray, & Kirschner, ), sensitivity analysis in ABMs (Alam et al, ), methods for increasing the computational efficiency of ABMs via “tuneable resolution” (Kirschner, Hunt, Marino, Fallahi‐Sichani, & Linderman, ), the use of Bayesian statistical model checking for parameter estimation in ABMs (Hussain et al, ), the use of optimization algorithms in conjunction with ABMs (Cicchese, Pienaar, Kirschner, & Linderman, ; R. C. Cockrell & An, ), the use of HPC (C. Cockrell & An, ; R. C. Cockrell & An, ; R. C. Cockrell et al, ; Petersen et al, ; Seekhao et al, ), strategies for data‐driven model validation (Renardy et al, ), and the incorporation of model‐based dynamic control discovery (R. C. Cockrell & An, ; Petersen et al, ). These are exciting developments that have, without a doubt, increased the range of biomedical problems and applications to which ABMs could be applied.…”

“…C. Cockrell & An, 2018), the use of HPC (C. Cockrell & An, 2017; R. C. Cockrell & An, 2018;R. C. Cockrell et al, 2015;Petersen et al, 2019;Seekhao et al, 2018), strategies for datadriven model validation (Renardy et al, 2019), and the incorporation of model-based dynamic control discovery (R. C. Cockrell & An, 2018;Petersen et al, 2019). These are exciting developments that have, without a doubt, increased the range of biomedical problems and applications to which ABMs could be applied.…”

“…This work was later extended to simulating surgical injury and validating the model against data obtained in rats (Li et al, , ). Recently, the lead author (Li‐Jessen) and her group extended this work further to modeling three‐dimensional vocal folds via the use of HPC to track a large number of cells and molecules, and used to simulate surgical injury (Seekhao et al, ).…”

“…This work was later extended to simulating surgical injury and validating the model against data obtained in rats (Li et al, 2010(Li et al, , 2011. Recently, the lead author (Li-Jessen) and her group extended this work further to modeling threedimensional vocal folds via the use of HPC to track a large number of cells and molecules, and used to simulate surgical injury (Seekhao et al, 2018). Solovyev et al (2013), Ziraldo, Gong, et al (2015) and Ziraldo, Solovyev, et al (2015) utilized ABMs to gain insights into the process of pressure ulcer formation in patients with spinal cord injuries.…”