Proceedings of the 3rd International Conference on Bio-Inspired Models of Network, Information and Computing Sytems
A parameter estimation approach for non-linear systems biology models using spline approximation
Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology
Component-based construction of bio-pathway models: The parameter estimation problem
Theoretical Computer Science
Hybrid Petri net based modeling for biological pathway simulation
Natural Computing: an international journal
Petri net models for the semi-automatic construction of large scale biological networks
Natural Computing: an international journal
Incremental signaling pathway modeling by data integration
RECOMB'10 Proceedings of the 14th Annual international conference on Research in Computational Molecular Biology
Composing globally consistent pathway parameter estimates through belief propagation
WABI'07 Proceedings of the 7th international conference on Algorithms in Bioinformatics
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Parameter estimation is a critical problem in modeling biological pathways. It is difficult because of the large number of parameters to be estimated and the limited experimental data available. In this paper, we propose a decompositional approach to parameter estimation. It exploits the structure of a large pathway model to break it into smaller components, whose parameters can then be estimated independently. This leads to significant improvements in computational efficiency. We present our approach in the context of Hybrid Functional Petri Net modeling and evolutionary search for parameter value estimation. However, the approach can be easily extended to other modeling frameworks and is independent of the search method used. We have tested our approach on a detailed model of the Akt and MAPK pathways with two known and one hypothesized crosstalk mechanisms. The entire model contains 84 unknown parameters. Our simulation results exhibit good correlation with experimental data, and they yield positive evidence in support of the hypothesized crosstalk between the two pathways. Contact: thiagu@comp.nus.edu.sg