Data-driven agent-based modelling of Trypanosoma collective behaviour

单细胞寄生虫布氏锥虫在采采蝇中肠中表现出线性排列的群集。在琼脂糖凝胶上的体外社会运动测定中，寄生虫的昆虫形式的殖民地显示出径向投影。集体行为的定量表征是可用的，但潜在的机制以及与体内情况的联系需要进一步的调查。我们解决这些问题的数据驱动的开发基于代理的集体行为模型来自Vicsek模型（Vicsek等，1995年）。考虑到物理和化学试剂-试剂和试剂-边界相互作用，我们测试了我们的主要假设，即锥虫的集体运动可以通过在边界处的负自动趋化性和寄生虫对齐的组合来再现。一个计算效率高的实现模型的编程语言朱莉娅允许模拟代理数量的寄生虫的数量在实验中。因此，模拟结果与实验数据的直接、定量比较是可行的。我们考虑了文献中的数据以及优先计划中的其他项目。通过与实验项目的合作，可以评估生物相关性。通过与寄生虫开发详细的流体动力学模拟项目的相互作用，在物理pronciples的近似模型的质量进行测试。在建立了一个适当的计算表示的准二维体外试验，我们将我们的代理商到三个空间维度，以建立一个链接到体内的情况。特别是，我们认为一个通道的流场，以及收缩和障碍，代表苍蝇肠。在这种情况下，我们的模型的分析提供了深入了解锥虫的集体行为的敏感性，以改变环境的几何形状。 在基于Agent的模型的开发过程中，我们强调通用性。为了形成更广泛采用我们的模型的基础，我们确定了优先计划中的三个拟议项目，这些项目调查了大群体个体的运动模式和相互作用，即小肠中的Heligmosomoides poligyrus，小肠中的Giardia muris和液滴中的恶性疟原虫微管蛋白二聚体。在这些系统上测试我们的建模方法有助于我们进一步理解寄生虫学中的一般物理概念。我们的项目有助于更详细地了解锥虫运动和微环境中与边界相互作用的物理学。此外，它还促进了其他寄生系统的类似研究。

The unicellular parasite Trypanosoma brucei exhibits swarming with linear alignment in the tsetse fly midgut. Colonies of the insect-form of the parasite show radial projections in in vitro social motility assays on agarose gel. Quantitative characterisations of the collective behaviour are available, but the underlying mechanisms as well as the link to the in vivo situation require further investigations. We address these questions by data-driven development of an agent-based model for collective behaviour derived from the Vicsek model (Vicsek et al. 1995). Considering physical as well as chemical agent-agent and agent-boundary interactions, we test our main hypothesis that collective motion of trypanosomes can be reproduced by a combination of negative auto-chemotaxis and parasite alignment at the boundary. A computationally efficient implementation of the model in the programming language Julia allows simulations for agent numbers comparable to the number of parasites in the experiments. Hence, a direct, quantitative comparison of the simulation results to experimental data is feasible. We consider both data from the literature as well as from other projects in the Priority Programme. Collaboration with experimental projects allows assessing the biological relevance. The model quality in terms of the approximation of physical pronciples is tested through interaction with projects that develop detailed hydrodynamic simulations of the parasite. Having established an appropriate computational representation of the quasi two-dimensional in vitro assay, we transfer our agents to three spatial dimensions to establish a link to the in vivo situation. In particular, we consider a channel with a flow field as well as constrictions and obstacles to represent the fly gut. Analysis of our model in this setting provides insight into the sensitivity of the collective behaviour of trypanosomes to changes of the environment geometry. During the development of the agent-based model, we place an emphasis on generality. To form the basis for a wider adoption of our model, we have identified three proposed projects in the Priority Programme that investigate the movement patterns and interactions of large groups of individuals, namely Heligmosomoides poligyrus in the small intestine, Giardia muris in the small intestine and Plasmodium falciparum tubulin dimers in liquid droplets. Testing our modelling approach on these systems helps to further our understanding of general physical concepts in parasitology. Our project contributes to a more detailed understanding of Trypanosoma locomotion and the physics of the interaction with boundaries in the microenvironment. In addition, it promotes similar studies in other parasitic systems.