Trace Simplifications Preserving Temporal Logic Formulae: Application to Oscillation Constraints between the Circadian Clock and the Cell Cycle

Pauline Traynard1 François Fages1 and Sylvain Soliman1

1 - Inria Paris-Rocquencourt, Team Lifeware, France

Winner of Best Student Paper Prize


Calibrating dynamical models on experimental data time series is a central task in computational systems biology. When numerical values for model parameters can be found to fit the data, the model can be used to make predictions, whereas the absence of any good fit may suggest to revisit the structure of the model and gain new insights in the biology of the system. Temporal logic provides a formal framework to deal with imprecise data and specify a wide variety of dynamical behaviors. It can be used to extract information from numerical traces coming from either experimental data or model simulations, and to specify the expected behaviors for model calibration. The computation time of the different methods depends on the number of points in the trace so the question of trace simplification is important to improve their performance. In this paper we study this problem and provide a series of trace simplifications which are correct to perform for some common temporal logic formulae. We give some general soundness theorems, and apply this approach to period and phase constraints on the circadian clock and the cell cycle. In this application, temporal logic patterns are used to compute the relevant characteristics of the experimental traces, and to measure the adequacy of the model to its specification on simulation traces. Speed-ups by several orders of magnitude are obtained by trace simplification even when produced by smart numerical integration methods.

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