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      FALCON: a toolbox for the fast contextualization of logical networks

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          Abstract

          Motivation

          Mathematical modelling of regulatory networks allows for the discovery of knowledge at the system level. However, existing modelling tools are often computation-heavy and do not offer intuitive ways to explore the model, to test hypotheses or to interpret the results biologically.

          Results

          We have developed a computational approach to contextualize logical models of regulatory networks with biological measurements based on a probabilistic description of rule-based interactions between the different molecules. Here, we propose a Matlab toolbox, FALCON, to automatically and efficiently build and contextualize networks, which includes a pipeline for conducting parameter analysis, knockouts and easy and fast model investigation. The contextualized models could then provide qualitative and quantitative information about the network and suggest hypotheses about biological processes.

          Availability and implementation

          FALCON is freely available for non-commercial users on GitHub under the GPLv3 licence. The toolbox, installation instructions, full documentation and test datasets are available at https://github.com/sysbiolux/FALCON. FALCON runs under Matlab (MathWorks) and requires the Optimization Toolbox.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

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          Most cited references15

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          Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood.

          Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model parameters are determined by the amount and quality of experimental data. This knowledge is essential for further investigation of model predictions. For this reason a major topic in modeling is identifiability analysis. We suggest an approach that exploits the profile likelihood. It enables to detect structural non-identifiabilities, which manifest in functionally related model parameters. Furthermore, practical non-identifiabilities are detected, that might arise due to limited amount and quality of experimental data. Last but not least confidence intervals can be derived. The results are easy to interpret and can be used for experimental planning and for model reduction. An implementation is freely available for MATLAB and the PottersWheel modeling toolbox at http://web.me.com/andreas.raue/profile/software.html. Supplementary data are available at Bioinformatics online.
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            Structural and functional analysis of cellular networks with CellNetAnalyzer

            Background Mathematical modelling of cellular networks is an integral part of Systems Biology and requires appropriate software tools. An important class of methods in Systems Biology deals with structural or topological (parameter-free) analysis of cellular networks. So far, software tools providing such methods for both mass-flow (metabolic) as well as signal-flow (signalling and regulatory) networks are lacking. Results Herein we introduce CellNetAnalyzer, a toolbox for MATLAB facilitating, in an interactive and visual manner, a comprehensive structural analysis of metabolic, signalling and regulatory networks. The particular strengths of CellNetAnalyzer are methods for functional network analysis, i.e. for characterising functional states, for detecting functional dependencies, for identifying intervention strategies, or for giving qualitative predictions on the effects of perturbations. CellNetAnalyzer extends its predecessor FluxAnalyzer (originally developed for metabolic network and pathway analysis) by a new modelling framework for examining signal-flow networks. Two of the novel methods implemented in CellNetAnalyzer are discussed in more detail regarding algorithmic issues and applications: the computation and analysis (i) of shortest positive and shortest negative paths and circuits in interaction graphs and (ii) of minimal intervention sets in logical networks. Conclusion CellNetAnalyzer provides a single suite to perform structural and qualitative analysis of both mass-flow- and signal-flow-based cellular networks in a user-friendly environment. It provides a large toolbox with various, partially unique, functions and algorithms for functional network analysis.CellNetAnalyzer is freely available for academic use.
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              Quantitative and logic modelling of molecular and gene networks.

              Behaviours of complex biomolecular systems are often irreducible to the elementary properties of their individual components. Explanatory and predictive mathematical models are therefore useful for fully understanding and precisely engineering cellular functions. The development and analyses of these models require their adaptation to the problems that need to be solved and the type and amount of available genetic or molecular data. Quantitative and logic modelling are among the main methods currently used to model molecular and gene networks. Each approach comes with inherent advantages and weaknesses. Recent developments show that hybrid approaches will become essential for further progress in synthetic biology and in the development of virtual organisms.
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                Author and article information

                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                01 November 2017
                29 June 2017
                29 June 2017
                : 33
                : 21
                : 3431-3436
                Affiliations
                [1 ]Systems Biology Group, Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg
                Author notes
                [* ]To whom correspondence should be addressed.
                [†]

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.

                [*]

                Associate Editor: Bonnie Berger

                Article
                btx380
                10.1093/bioinformatics/btx380
                5860161
                28673016
                239ac27f-a395-49a6-ac59-e0203a8a9631
                © The Author 2017. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 08 November 2016
                : 10 May 2017
                : 26 June 2017
                Page count
                Pages: 6
                Funding
                Funded by: FNR 10.13039/100007869
                Categories
                Original Papers
                Systems Biology

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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