Identifying control mechanisms of granuloma formation during M. tuberculosis infection using an agent-based model

A methodology for performing global uncertainty and sensitivity analysis in systems biology

“…Most uncertainty and sensitivity analysis techniques have been developed for use with deterministic models, such as those presented in previous sections of this work. To our knowledge, very few researchers have attempted extensive and systematic uncertainty and sensitivity analysis on ABMs (Lempert et al, 2002;Riggs et al, 2008;Segovia-Juarez et al, 2004).…”

“…As an example, we present a published ABM describing granuloma formation during Mycobacterium tuberculosis infection (Segovia-Juarez et al, 2004). This was the first ABM to use a modification of a US analysis using PRCC.…”

“…Parameters that we will analyze by US methods control initial conditions and rates or probabilities used to evaluate rules (Table IV). See (Segovia-Juarez et al, 2004) for a more detailed description of the model.…”

“…Figure 8 represents two typical scenarios: containment of infection and dissemination. The baseline set of parameter values differs between the two scenarios (see (Segovia-Juarez et al, 2004) for definitions of these scenarios and baseline parameters). The variability around each scenario is determined by aleatory uncertainty, while epistemic uncertainty causes the emergence of this bimodal outcome.…”

New insights into the function of granulomas in human tuberculosis

“…Different human models were recently established taking advantage of human cells and tissue. Segovia-Juarez et al developed an agentbased in vitro system in a cellular environment, suggesting that chemokine diffusion and prevention of macrophage 'overcrowding' in the system as well as T-cell recruitment are crucial prerequisites for granuloma formation [34]. Transmembrane TNF-α was investigated in a more recent study and seemed critical for early steps of granuloma formation, but not for long-term maintenance [35].…”