Agent-Based Modeling of Idiopathic Lung Fibrosis and Mechanistic Treatments

Abstract

Agent-based modeling (ABM) is a computational method for predicting the emergent outcomes of interacting, autonomous individuals in a complex system. Here, ABM is used to simulate interactions between fibroblast and myofibroblast cells during idiopathic pulmonary fibrosis (IPF) in alveolar tissue microenvironments. These microenvironments are derived from histology of a healthy human lung sample and moderate- and severe-IPF lung samples. Fibroblast differentiation, cell migration, and collagen secretion in response to the spatial distribution of the cytokine transforming growth factor-beta are captured in the ABM using NetLogo software. Results are presented from one simulated year without treatment and with mechanisms representing treatment by pirfenidone and pentoxifylline, alone and in combination. A total of 180 in silico experiments are run, analyzed, and compared in a high-throughput workflow. The effects of the initial number of fibroblasts and treatment scenarios on various metrics related to collagen accumulation and collagen invasion into alveolar regions are determined. The ABM and the analysis files are shared to facilitate model reuse. By integrating computational modeling of IPF and therapeutics, this research aims to improve understanding of fibrosis progression and assess the efficacy of novel and existing treatments targeting different mechanisms to inform decision-making for IPF treatment.