Towards Argument-Driven Validation of an in silico Model of Immune Tissue Organogenesis

摘要

Specialised tissues of the immune system including lymph nodes, tonsils, spleen and Peyer's Patches have key roles in the initiation of adaptive immune responses to infection. To understand the molecular mechanisms involved in the development of this tissue, mice deficient for key genes in this process have been developed and analysed, leading to a basic model describing tissue formation. Although this approach has provided some key insights into the molecular mechanisms involved, due to the complexity of gene expression patterns it has not been possible to fully understand the process of lymphoid tissue organogenesis. In an attempt to further explore the mechanisms involved, we intend to utilise an iterative approach which combines imaging, gene expression, and gene-knockout data with stochastic multi-agent modelling. We have developed an agent-based simulation with which we can investigate the effect of the molecular and biophysical mechanisms involved in such complex biological systems. Our simulation captures the development of Peyer's Patches (PP), specialised lymphoid tissue found within the intestine which plays a key role in the induction of antibody responses to pathogenic bacteria and viruses in the gut [1,2]. This tissue forms during embryonic development as a result of a stochastic process which leads to the formation of 8-12 PP in mice, and around 300 PP in humans [3]. We have found that results from our agent-based simulation do not exactly match those seen in vivo. However, we believe that this will often be the case for computer simulations of biology that simplify various aspects of the real system. Consequently, we need to explain and justify how the simulation results have been generated so that these results can be interpreted in the context of the real biological system. We describe in this abstract how we plan to apply goal-structuring notation (an argumentation technique) to provide this explanation and justification.