A computational model of invasive aspergillosis in the lung and the role of iron.

BACKGROUND: Invasive aspergillosis is a severe infection of immunocompromised hosts, caused by the inhalation of the spores of the ubiquitous environmental molds of the Aspergillus genus. The innate immune response in this infection entails a series of complex and inter-related interactions between multiple recruited and resident cell populations with each other and with the fungal cell; in particular, iron is critical for fungal growth. RESULTS: A computational model of invasive aspergillosis is presented here; the model can be used as a rational hypothesis-generating tool to investigate host responses to this infection. Using a combination of laboratory data and published literature, an in silico model of a section of lung tissue was generated that includes an alveolar duct, adjacent capillaries, and surrounding lung parenchyma. The three-dimensional agent-based model integrates temporal events in fungal cells, epithelial cells, monocytes, and neutrophils after inhalation of spores with cellular dynamics at the tissue level, comprising part of the innate immune response. Iron levels in the blood and tissue play a key role in the fungus' ability to grow, and the model includes iron recruitment and consumption by the different types of cells included. Parameter sensitivity analysis suggests the model is robust with respect to unvalidated parameters, and thus is a viable tool for an in silico investigation of invasive aspergillosis. CONCLUSIONS: Using laboratory data from a mouse model of invasive aspergillosis in the context of transient neutropenia as validation, the model predicted qualitatively similar time course changes in fungal burden, monocyte and neutrophil populations, and tissue iron levels. This model lays the groundwork for a multi-scale dynamic mathematical model of the immune response to Aspergillus species.

Optimal harvesting for a predator-prey agent-based model using difference equations.

In this paper, a method known as Pareto optimization is applied in the solution of a multi-objective optimization problem. The system in question is an agent-based model (ABM) wherein global dynamics emerge from local interactions. A system of discrete mathematical equations is formulated in order to capture the dynamics of the ABM; while the original model is built up analytically from the rules of the model, the paper shows how minor changes to the ABM rule set can have a substantial effect on model dynamics. To address this issue, we introduce parameters into the equation model that track such changes. The equation model is amenable to mathematical theory­we show how stability analysis can be performed and validated using ABM data. We then reduce the equation model to a simpler version and implement changes to allow controls from the ABM to be tested using the equations. Cohen's weighted κ is proposed as a measure of similarity between the equation model and the ABM, particularly with respect to the optimization problem. The reduced equation model is used to solve a multi-objective optimization problem via a technique known as Pareto optimization, a heuristic evolutionary algorithm. Results show that the equation model is a good fit for ABM data; Pareto optimization provides a suite of solutions to the multi-objective optimization problem that can be implemented directly in the ABM.