The Input Signal Step Function (ISSF), a standard method to encode input signals in SBML models with software support, applied to circadian clock models.

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TitleThe Input Signal Step Function (ISSF), a standard method to encode input signals in SBML models with software support, applied to circadian clock models.
Publication TypeJournal Article
Year of Publication2012
AuthorsAdams, RR, Tsorman, N, Stratford, K, Akman, OE, Gilmore, S, Juty, N, Le Novère, N, Millar, AJ, Millar, AJ
JournalJ Biol Rhythms
Volume27
Issue4
Pagination328-32
Date Published2012 Aug
ISSN1552-4531
KeywordsAlgorithms, Animals, Circadian Clocks, Circadian Rhythm, Computational Biology, Models, Biological, Programming Languages, Reproducibility of Results, Software
Abstract

<p>Time-dependent light input is an important feature of computational models of the circadian clock. However, publicly available models encoded in standard representations such as the Systems Biology Markup Language (SBML) either do not encode this input or use different mechanisms to do so, which hinders reproducibility of published results as well as model reuse. The authors describe here a numerically continuous function suitable for use in SBML for models of circadian rhythms forced by periodic light-dark cycles. The Input Signal Step Function (ISSF) is broadly applicable to encoding experimental manipulations, such as drug treatments, temperature changes, or inducible transgene expression, which may be transient, periodic, or mixed. It is highly configurable and is able to reproduce a wide range of waveforms. The authors have implemented this function in SBML and demonstrated its ability to modify the behavior of publicly available models to accurately reproduce published results. The implementation of ISSF allows standard simulation software to reproduce specialized circadian protocols, such as the phase-response curve. To facilitate the reuse of this function in public models, the authors have developed software to configure its behavior without any specialist knowledge of SBML. A community-standard approach to represent the inputs that entrain circadian clock models could particularly facilitate research in chronobiology.</p>

DOI10.1177/0748730412451077
Alternate JournalJ. Biol. Rhythms
PubMed ID22855577
PubMed Central IDPMC3423168
Grant ListBB/D019621/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/E015263/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/F005237/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/F010583/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom