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RACIPE: a computational tool for modeling gene regulatory circuits using randomization

BACKGROUND: One of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, espe...

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Autores principales: Huang, Bin, Jia, Dongya, Feng, Jingchen, Levine, Herbert, Onuchic, José N., Lu, Mingyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006707/
https://www.ncbi.nlm.nih.gov/pubmed/29914482
http://dx.doi.org/10.1186/s12918-018-0594-6
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author Huang, Bin
Jia, Dongya
Feng, Jingchen
Levine, Herbert
Onuchic, José N.
Lu, Mingyang
author_facet Huang, Bin
Jia, Dongya
Feng, Jingchen
Levine, Herbert
Onuchic, José N.
Lu, Mingyang
author_sort Huang, Bin
collection PubMed
description BACKGROUND: One of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, especially for large networks. RESULTS: We present a user-friendly computational tool for the community to use our newly developed method named random circuit perturbation (RACIPE), to explore the robust dynamical features of gene regulatory circuits without the requirement of detailed kinetic parameters. Taking the network topology as the only input, RACIPE generates an ensemble of circuit models with distinct randomized parameters and uniquely identifies robust dynamical properties by statistical analysis. Here, we discuss the implementation of the software and the statistical analysis methods of RACIPE-generated data to identify robust gene expression patterns and the functions of genes and regulatory links. Finally, we apply the tool on coupled toggle-switch circuits and a published circuit of B-lymphopoiesis. CONCLUSIONS: We expect our new computational tool to contribute to a more comprehensive and unbiased understanding of mechanisms underlying gene regulatory networks. RACIPE is a free open source software distributed under (Apache 2.0) license and can be downloaded from GitHub (https://github.com/simonhb1990/RACIPE-1.0). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12918-018-0594-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-60067072018-06-26 RACIPE: a computational tool for modeling gene regulatory circuits using randomization Huang, Bin Jia, Dongya Feng, Jingchen Levine, Herbert Onuchic, José N. Lu, Mingyang BMC Syst Biol Software BACKGROUND: One of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, especially for large networks. RESULTS: We present a user-friendly computational tool for the community to use our newly developed method named random circuit perturbation (RACIPE), to explore the robust dynamical features of gene regulatory circuits without the requirement of detailed kinetic parameters. Taking the network topology as the only input, RACIPE generates an ensemble of circuit models with distinct randomized parameters and uniquely identifies robust dynamical properties by statistical analysis. Here, we discuss the implementation of the software and the statistical analysis methods of RACIPE-generated data to identify robust gene expression patterns and the functions of genes and regulatory links. Finally, we apply the tool on coupled toggle-switch circuits and a published circuit of B-lymphopoiesis. CONCLUSIONS: We expect our new computational tool to contribute to a more comprehensive and unbiased understanding of mechanisms underlying gene regulatory networks. RACIPE is a free open source software distributed under (Apache 2.0) license and can be downloaded from GitHub (https://github.com/simonhb1990/RACIPE-1.0). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12918-018-0594-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-19 /pmc/articles/PMC6006707/ /pubmed/29914482 http://dx.doi.org/10.1186/s12918-018-0594-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Software
Huang, Bin
Jia, Dongya
Feng, Jingchen
Levine, Herbert
Onuchic, José N.
Lu, Mingyang
RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title_full RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title_fullStr RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title_full_unstemmed RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title_short RACIPE: a computational tool for modeling gene regulatory circuits using randomization
title_sort racipe: a computational tool for modeling gene regulatory circuits using randomization
topic Software
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006707/
https://www.ncbi.nlm.nih.gov/pubmed/29914482
http://dx.doi.org/10.1186/s12918-018-0594-6
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