Conclusion: To accomplish the objective in Section 7.1, we discussed the importance of a biological processes development environment that can easily and smoothly support (i) modeling of biological processes, (ii) simulation of biological processes, (iii) visualization of their simulations, and (iv) integration of existing biological pathway databases for modeling, and we developed their applications, (i/ii) GON, GONML, (iii) Visualizer, and (iv) BPE, BPEOS, while developing the new Petri net-based architecture HFPN/HFPNe that is suitable for modeling and simulation of complex biological processes. It must be noted that in our development environment, one unknown biological phenomenon in multicellular systems was discovered (Matsuno et al., 2003b). In Matsuno et al. (2003b), the mechanism of Notch-dependent boundary formation in the Drosophila large intestine is analyzed by comparing experimental manipulation of Delta expression with modeling and simulation results in our development environment. Boundary formation representing the situation in normal large intestine was shown by the simulation. By manipulating the Delta expression in the large intestine, a few types of disorder in boundary cell differentiation were observed, and similar abnormal patterns were generated by the simulation. These simulation results suggest that values of parameters which represent the strength of cell-autonomous suppression of Notch signaling by Delta are essential for generating two different modes of patterning; lateral inhibition and boundary formation, which could explain how a common gene regulatory network results in two different patterning modes in vivo. The fact that the discovery was accomplished in our environment is important. Another important thing is the process of discovery; the project members, mainly Matsuno and members of the Murakami developmental biology laboratory, have weekly communicated the biological processes by modeling and simulating in our development environment, the GON and Visualizer. These two facts reveal comprising the concepts of our objective are important, and our architecture and applications are acceptable in actual research fields.
ASJC Scopus subject areas
- Computer Science(all)