EpiLog: A software for the logical modelling of epithelial dynamics

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Cellular responses are governed by regulatory networks subject to external signals from surrounding cells and to other micro-environmental cues. The logical (Boolean or multi-valued) framework proved well suited to study such processes at the cellular level, by specifying qualitative models of involved signalling pathways and gene regulatory networks.

Here, we describe and illustrate the main features of EpiLog, a computational tool that implements an extension of the logical framework to the tissue level. EpiLog defines a collection of hexagonal cells over a 2D grid, which embodies a mono-layer epithelium. Basically, it defines a cellular automaton in which cell behaviours are driven by associated logical models subject to external signals.

EpiLog is freely available on the web at http://epilog-tool.org. It is implemented in Java (version ≥1.7 required) and the source code is provided at https://github.com/epilog-tool/epilog under a GNU General Public License v3.0.

Related collections

Most cited references 22

Record: found
Abstract: found
Article: not found

Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle.

A. Faure, A Naldi, C Chaouiya … (2006)

To understand the behaviour of complex biological regulatory networks, a proper integration of molecular data into a full-fledge formal dynamical model is ultimately required. As most available data on regulatory interactions are qualitative, logical modelling offers an interesting framework to delineate the main dynamical properties of the underlying networks. Transposing a generic model of the core network controlling the mammalian cell cycle into the logical framework, we compare different strategies to explore its dynamical properties. In particular, we assess the respective advantages and limits of synchronous versus asynchronous updating assumptions to delineate the asymptotical behaviour of regulatory networks. Furthermore, we propose several intermediate strategies to optimize the computation of asymptotical properties depending on available knowledge. The mammalian cell cycle model is available in a dedicated XML format (GINML) on our website, along with our logical simulation software GINsim (http://gin.univ-mrs.fr/GINsim). Higher resolution state transitions graphs are also found on this web site (Model Repository page).

0 comments Cited 185 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems

Ahmadreza Ghaffarizadeh, Randy Heiland, Samuel H. Friedman … (2018)

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal “virtual laboratory” for such multicellular systems simulates both the biochemical microenvironment (the “stage”) and many mechanically and biochemically interacting cells (the “players” upon the stage). PhysiCell—physics-based multicellular simulator—is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility “out of the box.” The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a “cellular cargo delivery” system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant independent code base for replicating results from other simulation platforms. The PhysiCell source code, examples, documentation, and support are available under the BSD license at http://PhysiCell.MathCancer.org and http://PhysiCell.sf.net.

0 comments Cited 109 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Logical Modeling and Dynamical Analysis of Cellular Networks

Wassim Abou-Jaoudé, Pauline Traynard, Pedro T. Monteiro … (2016)

The logical (or logic) formalism is increasingly used to model regulatory and signaling networks. Complementing these applications, several groups contributed various methods and tools to support the definition and analysis of logical models. After an introduction to the logical modeling framework and to several of its variants, we review here a number of recent methodological advances to ease the analysis of large and intricate networks. In particular, we survey approaches to determine model attractors and their reachability properties, to assess the dynamical impact of variations of external signals, and to consistently reduce large models. To illustrate these developments, we further consider several published logical models for two important biological processes, namely the differentiation of T helper cells and the control of mammalian cell cycle.

0 comments Cited 89 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Pedro L. Varela: Role: SoftwareRole: Writing – Original Draft PreparationRole: Writing – Review & Editing

Camila V. Ramos: Role: SoftwareRole: Writing – Review & Editing

Pedro T. Monteiro: Role: Funding AcquisitionRole: SoftwareRole: SupervisionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing

ORCID: https://orcid.org/0000-0002-7934-5495

Claudine Chaouiya: Role: ConceptualizationRole: Funding AcquisitionRole: SupervisionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing

ORCID: https://orcid.org/0000-0003-2350-0756

Journal

Journal ID (nlm-ta): F1000Res

Journal ID (iso-abbrev): F1000Res

Journal ID (pmc): F1000Research

Title: F1000Research

Publisher: F1000 Research Limited (London, UK )

ISSN (Electronic): 2046-1402

Publication date (Electronic): 11 March 2019

Publication date Collection: 2018

Volume: 7

Electronic Location Identifier: 1145

Affiliations

[1 ]Instituto Superior Técnico, Universidade de Lisboa, Lisbon, P-1049-001, Portugal

[2 ]INESC-ID, Lisbon, P-1000-029, Portugal

[3 ]Instituto Gulbenkian de Ciência, Oeiras, P-2780-156, Portugal

[4 ]CNRS, Centrale Marseille, l'Institut de Mathématiques de Marseille, Aix-Marseille University, Marseille, France

[1 ]Institut Curie, Inserm U900, Mines Paris Tech, PSL Research University, Paris, France

[2 ]Barcelona Supercomputing Center (BSC), Barcelona, Spain

[1 ]Institut Curie, Inserm U900, Mines Paris Tech, PSL Research University, Paris, France

[2 ]Barcelona Supercomputing Center (BSC), Barcelona, Spain

IGC, Portugal

[1 ]Bioprocess Engineering Group, IIM-CSIC, Vigo, Spain

[2 ]Bioprocess Engineering Group, IIM-CSIC, Vigo, Spain

IGC, Portugal

[1 ]Department of Computer Science, Oslo Metropolitan University, Oslo, Norway

IGC, Portugal

Author notes

[a ] Pedro.Tiago.Monteiro@ 123456tecnico.ulisboa.pt

[b ] chaouiya@ 123456igc.gulbenkian.pt

No competing interests were disclosed.

Competing interests: No competing interests were disclosed.

Author information

Pedro T. Monteiro https://orcid.org/0000-0002-7934-5495

Claudine Chaouiya https://orcid.org/0000-0003-2350-0756

Article

DOI: 10.12688/f1000research.15613.2

PMC ID: 6173114

PubMed ID: 30363398

SO-VID: 2db84a59-1449-4e96-a747-c2dd933b0a19

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date accepted : 1 March 2019

Funding

Funded by: Fundação para a Ciência e a Tecnologia

Funded by: Fundação Calouste Gulbenkian

This work was supported by national funds through Fundação para Ciência e a Tecnologia (FCT) with reference PTDC/BEX-BCB/0772/2014, UID/CEC/50021/2013 and IF/01333/2013. PV was supported by grant PTDC/BEX-BCB/0772/2014 and PTDC/EIA-CCO/099229/2008. CR was supported by PTDC/BEX-BCB/0772/2014 and IF/01333/2013/CP1204/CT0001. Furthermore, CC and CR acknowledge support from the Fundação Calouste Gulbenkian.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

EpiLog: A software for the logical modelling of epithelial dynamics

Read this article at

Abstract

Related collections

Software for SAXS correction and analysis

Most cited references 22

Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle.

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems

Logical Modeling and Dynamical Analysis of Cellular Networks

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 162

Cited by 4

Most referenced authors 197