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Multiscale Modeling and Analysis of Planar Cell Polarity in the Drosophila Wing

2012; Institute of Electrical and Electronics Engineers; Volume: 10; Issue: 2 Linguagem: Inglês

10.1109/tcbb.2012.101

2374-0043

Qian Gao, David Gilbert, Monika Heiner, Fei Liu, Daniele Maccagnola, David Tree,

Bioinformatics and Genomic Networks

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.