TL;DR
This paper introduces a graph-based method for validating dynamical system models using time series data, enabling model rejection and parameter reduction through pattern matching.
Contribution
It presents a novel approach combining labeled path matching in graphs with model validation, applicable to biological regulatory networks.
Findings
The method can invalidate models when no matching pattern is found.
Application to yeast gene regulatory models demonstrates practical utility.
Provides theoretical guarantees for model validation based on pattern matching.
Abstract
We show how a graph algorithm for finding matching labeled paths in pairs of labeled directed graphs can be used to perform model validation for a class of dynamical systems including regulatory network models of relevance to systems biology. In particular, we extract a partial order of events describing local minima and local maxima of observed quantities from experimental time-series data from which we produce a labeled directed graph we call the pattern graph for which every path from root to leaf corresponds to a plausible sequence of events. We then consider the regulatory network model, which can be itself rendered into a labeled directed graph we call the search graph via techniques previously developed in computational dynamics. Labels on the pattern graph correspond to experimentally observed events, while labels on the search graph correspond to mathematical facts about the…
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Dr. Breschine Cummins
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Dear Editors of SIADS, On behalf of my coauthors, T. Gedeon, S. Harker, and K. Mischaikow, I offer for submission the manuscript “Model rejection and parameter reduction via time series.” This work describes a method for comparing robust characteristics of time series data to mechanistic models of regulatory interactions between the observed species. The technique allows the rejection of hypothesized regulatory networks, and moreover eliminates large swaths of parameter space from network models that cannot be rejected. Network model and parameter pairs that are not rejected are consistent with the partial order of maxima and minima seen across the dataset. This method is appropriate for noisy data, and we apply it to four known regulators of the cell cycle of the yeast S. cerevisiae as proof of concept.
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Sincerely,
