Comput Math Methods Med - Modeling innate immune response to early Mycobacterium infection.

Tópicos

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Resumo

In the study of complex patterns in biology, mathematical and computational models are emerging as important tools. In addition to experimental approaches, these modeling tools have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to mycobacterial infection and tuberculous granuloma formation. We present an approach in which a computational model represents the interaction of the Mycobacterium infection with the innate immune system in zebrafish at a high level of abstraction. We use the Petri Net formalism to model the interaction between the key host elements involved in granuloma formation and infection dissemination. We define a qualitative model for the understanding and description of causal relations in this dynamic process. Complex processes involving cell-cell or cell-bacteria communication can be modeled at smaller scales and incorporated hierarchically into this main model; these are to be included in later elaborations. With the infection mechanism being defined on a higher level, lower-level processes influencing the host-pathogen interaction can be identified, modeled, and tested both quantitatively and qualitatively. This systems biology framework incorporates modeling to generate and test hypotheses, to perform virtual experiments, and to make experimentally verifiable predictions. Thereby it supports the unraveling of the mechanisms of tuberculosis infection.

Resumo Limpo

studi complex pattern biolog mathemat comput model emerg import tool addit experiment approach model tool recent appli address open question regard hostpathogen interact dynam includ immun respons mycobacteri infect tubercul granuloma format present approach comput model repres interact mycobacterium infect innat immun system zebrafish high level abstract use petri net formal model interact key host element involv granuloma format infect dissemin defin qualit model understand descript causal relat dynam process complex process involv cellcel cellbacteria communic can model smaller scale incorpor hierarch main model includ later elabor infect mechan defin higher level lowerlevel process influenc hostpathogen interact can identifi model test quantit qualit system biolog framework incorpor model generat test hypothes perform virtual experi make experiment verifi predict therebi support unravel mechan tuberculosi infect

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