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

Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data...

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Main Authors: Aman Garg, Samson Yuen, Nuttiiya Seekhao, Grace Yu, Jeannie A. C. Karwowski, Michael Powell, Jon T. Sakata, Luc Mongeau, Joseph JaJa, Nicole Y. K. Li-Jessen
Format: Article
Language:English
Published: MDPI AG 2019-07-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/9/15/2974
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author Aman Garg
Samson Yuen
Nuttiiya Seekhao
Grace Yu
Jeannie A. C. Karwowski
Michael Powell
Jon T. Sakata
Luc Mongeau
Joseph JaJa
Nicole Y. K. Li-Jessen
author_facet Aman Garg
Samson Yuen
Nuttiiya Seekhao
Grace Yu
Jeannie A. C. Karwowski
Michael Powell
Jon T. Sakata
Luc Mongeau
Joseph JaJa
Nicole Y. K. Li-Jessen
author_sort Aman Garg
collection DOAJ
description Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.
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spelling doaj.art-0b8f8bc9431f4cacbd40a19945fcc7b82022-12-21T18:51:09ZengMDPI AGApplied Sciences2076-34172019-07-01915297410.3390/app9152974app9152974Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and VerificationAman Garg0Samson Yuen1Nuttiiya Seekhao2Grace Yu3Jeannie A. C. Karwowski4Michael Powell5Jon T. Sakata6Luc Mongeau7Joseph JaJa8Nicole Y. K. Li-Jessen9Department of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, CanadaSchool of Communication Sciences and Disorders, McGill University, Montreal, QC H3A 1G1, CanadaDepartment of Electrical and Computer Engineering, University of Maryland, College Park, MD 20742, USASchool of Communication Sciences and Disorders, McGill University, Montreal, QC H3A 1G1, CanadaThis author currently has no affiliation.Virginia Tech Carilion Research Institute, Roanoke, VA 24016, USADepartment of Biology, McGill University, Montreal, QC H3A 1G1, CanadaDepartment of Mechanical Engineering, McGill University, Montreal, QC H3A 0G4, CanadaDepartment of Electrical and Computer Engineering, University of Maryland, College Park, MD 20742, USADepartment of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, CanadaAgent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.https://www.mdpi.com/2076-3417/9/15/2974vocal foldscomputational medicineagent-based modeling
spellingShingle Aman Garg
Samson Yuen
Nuttiiya Seekhao
Grace Yu
Jeannie A. C. Karwowski
Michael Powell
Jon T. Sakata
Luc Mongeau
Joseph JaJa
Nicole Y. K. Li-Jessen
Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
Applied Sciences
vocal folds
computational medicine
agent-based modeling
title Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
title_full Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
title_fullStr Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
title_full_unstemmed Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
title_short Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification
title_sort towards a physiological scale of vocal fold agent based models of surgical injury and repair sensitivity analysis calibration and verification
topic vocal folds
computational medicine
agent-based modeling
url https://www.mdpi.com/2076-3417/9/15/2974
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