SEGMEnT and Anatomic Scale Modeling
SEGMEnT (Spatially Explicit General-Purpose Model of Enteric Tissue) is an agent-based model that incorporates gut epithelial cells, inflammatory cells (macrophages and neutrophils), and their effects on the extracellular matrix with consequent changes in crypt-villus morphology. Cells communicate with each other and their environment through a cytokine signaling network.
Simulations with SEGMEnT fall into three categories: 1) representing the baseline healthy state of the gut mucosa, 2) reproducing previously published single-molecule inhibition or gene knockout experiments, and 3) reproducing specific patho-physiological conditions. SEGMEnT reproduces multiple different system-level/cell population phenotypes. These phenotypes can be used as objective functions to constrain model behavior for parameter space exploration, as well as when additional cellular-molecular detail is added. Spatial gradients exist for morphogens such as Wnt, extracellular bone morphogenic protein (BMP), BMP activity, Ephrin-B ligand/EphB receptor activity, sonic hedgehog (Hh), and β-catenin. The cellular components of the epithelium undergo a complete renewal every five days. In addition to reproducing baseline normal mucosal homeostasis, SEGMEnT is also able to reproduce several pathophysiological conditions related to inflammation and produce the corresponding altered tissue patterning, such as tissue injury and reconstitution and response intestinal ischemia and reperfusion. Also, notably, SEGMEnT was used to simulate the generation of pouch metaplasia arising from persistent, low-level inflammatory signaling as would be seen in luminal stasis and bacterial overgrowth in an ileal pouch.
1. Cockrell, Chase, Scott Christley, and Gary An. "Investigation of inflammation and tissue patterning in the gut using a spatially explicit general-purpose model of enteric tissue (SEGMEnT)." PLoS computational biology 10, no. 3 (2014): e1003507.
2. Cockrell, Robert Chase, Scott Christley, Eugene Chang, and Gary An. "Towards anatomic scale agent-based modeling with a massively parallel spatially explicit general-purpose model of enteric tissue (SEGMEnT_HPC)." PloS one 10, no. 3 (2015): e0122192.