Domijan, Mirela, Brown, Paul E., Shulgin, Boris V. and Rand, D. A. (David A.) (2016) PeTTSy : a computational tool for perturbation analysis of complex systems biology models. BMC Bioinformatics, 17 (124). doi:10.1186/s12859-016-0972-2 ISSN 1471-2105.

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Abstract

Background
Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary.

Results
Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems.

To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters.

Conclusions
PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and signalling systems. It allows for simulation and analysis of models under a variety of environmental conditions and for experimental optimisation of complex combined experiments. With its unique set of tools it makes a valuable addition to the current library of sensitivity analysis toolboxes. We believe that this software will be of great use to the wider biological, systems biology and modelling communities.

Item Type:	Journal Article
Alternative Title:
Subjects:	Q Science > QA Mathematics Q Science > QH Natural history T Technology > TA Engineering (General). Civil engineering (General)
Divisions:	Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Library of Congress Subject Headings (LCSH):	Perturbation (Mathematics), Dynamics, Mathematical models , Gene regulatory networks
Journal or Publication Title:	BMC Bioinformatics
Publisher:	BioMed Central Ltd.
ISSN:	1471-2105
Official Date:	10 March 2016
Dates:	Date Event 10 March 2016 Available 28 February 2016 Accepted 24 September 2015 Submitted
Volume:	17
Number:	124
DOI:	10.1186/s12859-016-0972-2
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	9 March 2016
Date of first compliant Open Access:	28 June 2016
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Seventh Framework Programme (European Commission) (FP7)
Grant number:	(BBF0059381 (BBSRC), BBF0058141 (BBSRC), BB/F005261/1 (BBSRC), BB/K003097/1 (BBSRC), EP/C544587/1 (EPSRC), 305564 (FP7)
Is Part Of:	Biotechnology and Biological Sciences Research Council (GB) (BBF0059381) Prof David A Rand Biotechnology and Biological Sciences Research Council (GB) (BBF0058141 BB) Prof David A Rand Engineering and Physical Sciences Research Council (GB) (EP/C544587/1) Prof David A Rand Seventh Framework Programme (BE) (FP7/2007-2013) Prof David A Rand Biotechnology and Biological Sciences Research Council (GB) (BB/F005261/1) Prof David A Rand Biotechnology and Biological Sciences Research Council (GB) (BB/K003097/1)

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