Optimisation and Landscape Analysis of Computational Biology Models: A Case Study
Association for Computing Machinery (ACM)
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Reason for embargo
Embargoed until after conference
The parameter explosion problem is a crucial bottleneck in modelling gene regulatory networks (GRNs), limiting the size of models that can be optimised to experimental data. By discretising state, but not time, Boolean delay equations (BDEs) provide a signi ficant reduction in parameter numbers, whilst still providing dynamical complexity comparable to more biochemically detailed models, such as those based on differential equations. Here, we explore several approaches to optimising BDEs to timeseries data, using a simple circadian clock model as a case study. We compare the ffectiveness of two optimisers on our problem: a genetic algorithmf(GA) and an elite accumulative sampling (EAS) algorithm that provides robustness to data discretisation. Our results show that both methods are able to distinguish effectively between alternative architectures, yielding excellent ts to data. We also perform a landscape analysis, providing insights into the properties that determine optimiser performance (e.g. number of local optima and basin sizes). Our results provide a promising platform for the analysis of more complex GRNs, and suggest the possibility of leveraging cost landscapes to devise more effi cient optimisation schemes.
This work was financially supported by the Engineering and Physical Sciences Research Council [grant numbers EP/N017846/1, EP/N014391/1], and made use of the Zeus and Isca supercomputing facilities provided by the University of Exeter HPC Strategy.
This is the author accepted manuscript. The final version is available from ACM via the DOI in this record.
GECCO 2017: Genetic and Evolutionary Computation Conference, 15-19 July 2017, Berlin, Germany