An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Abstract

We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as “sepsis”. Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-α ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies.

Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation

“…We used NetLogo 5.3.1 (Netlogo 2014), a platform with a simplified programing environment, easily implemented tool sets, and well-established documentation support, to implement this ABM (Shi, Wu, and Ben-Arieh 2014;Shi et al 2016). The primary user interface of NetLogo is comprised of twodimensional (2 D) grids, in which agents can be divided into two categories: "patches" and "turtles."…”

“…"Patches" are fixed agents placed on background grids in the model workspace. "Turtles" are mobile agents that can occupy a position or move freely on the surface of patches and execute certain functions or actions regulated by the simulated system (Shi et al 2016). The interface of NetLogo allows a modeler to set initial parameters and observe simulation results.…”

Ultrasonic-Assisted Pelleting of Sorghum Stalk: Predictive Models for Pellet Density and Durability Using Multiple Response Surface Methodology

“…RSM has been successfully used and applied in many diverse areas such as biotechnology [44,45], chemical engineering [46,47], biofuel production [48], energy consumption [49], plant protection [50,51], and clinical practice [52,53]. One major contribution of this methodology is to investigate and quantify the relationships between a set of input variables and outputs of interest.…”

Mathematical Model for Two-Spotted Spider Mites System: Verification and Validation

“…For a future research, we plan to develop an agent-based model [24] [25] [26] to simulate interactions and predict the key parameters in order to offer suggestions on controlling the number of predators. Also, future expansion of this research can consider applying optimal control theory [27] [28] to provide decision makers with better policies of controlling the population of the two-spotted spider mites.…”