School of Information Systems, Computing, and Mathematics, Brunel University, DISC, St Johns Building, Uxbridge UB8 3PH, United Kingdom.
IEEE/ACM Trans Comput Biol Bioinform. 2013 Mar-Apr;10(2):337-51. doi: 10.1109/TCBB.2012.101.
Modeling across multiple scales is a current challenge in Systems Biology, especially when applied to multicellular organisms. In this paper, we present an approach to model at different spatial scales, using the new concept of Hierarchically Colored Petri Nets (HCPN). We apply HCPN to model a tissue comprising multiple cells hexagonally packed in a honeycomb formation in order to describe the phenomenon of Planar Cell Polarity (PCP) signaling in Drosophila wing. We have constructed a family of related models, permitting different hypotheses to be explored regarding the mechanisms underlying PCP. In addition our models include the effect of well-studied genetic mutations. We have applied a set of analytical techniques including clustering and model checking over time series of primary and secondary data. Our models support the interpretation of biological observations reported in the literature.
跨多尺度建模是系统生物学当前面临的挑战，特别是在应用于多细胞生物时。在本文中，我们提出了一种在不同空间尺度上建模的方法，使用新的层次彩色 Petri 网（HCPN）概念。我们应用 HCPN 来对由多个六边形细胞组成的组织进行建模，以描述果蝇翅膀中平面细胞极性（PCP）信号的现象。我们构建了一系列相关模型，允许针对 PCP 潜在机制的不同假设进行探索。此外，我们的模型还包括了已被深入研究的遗传突变的影响。我们应用了一组分析技术，包括聚类和随时间对主要和次要数据的模型检查。我们的模型支持对文献中报告的生物学观察结果的解释。
