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Rheumatoid arthritis

Rheumatoid Arthritis Map (RA-MAP)

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that causes chronic inflammation of the joints. The etiology of the disease remains still unclear. Patients with autoimmune diseases have an immune system that targets and attacks their own body tissues. Characteristic features of RA include inflammation of the tissue around the joints and hyperplasia (swelling) that can lead to bone erosion and permanent deformity. The disease can affect multiple organs in the body causing inflammation and injury and for this it is considered a systemic illness.

RA affects approximately 1% of the worldwide population. Women have a two to three higher risk developing the disease in comparison to men. It is currently believed that RA initiates as a result of complex interactions between genetic and environmental factors and that these factors are responsible for susceptibility and phenotype.

All cellular processes can be depicted as, and characterized by, their underlying complex molecular networks. This fundamental concept of viewing cells has brought up the need to develop high-quality methodologies for the construction and subsequent analysis of these molecular networks at a systems level. Quantitative kinetic models using differential or stochastic equations can provide a detailed analysis of a network’s dynamics, but they require a number of parameters that is often prohibitively large. In order to address the scarcity of kinetic data in signalling pathways, the use of discrete logic-based models is proposed as an alternative way to study the system’s qualitative dynamic behavior.

The University of Evry, Paris Saclay is working on an updated, detailed, fully annotated molecular map for RA based on exhaustive curation of the existing literature using CellDesigner. This map will serve as a template for the construction of a qualitative dynamical model, in order to explore the dynamical properties of the system and analyze its underlying regulatory networks. The model will then be used to address different biological questions such as comparing the network for different phenotypes, trying to understand the mechanisms driving variable responses to treatment and investigating the role of co- and multi-morbidities.

The construction of a map and of a dynamic model are two tasks with different purposes that are today mainly performed in an independent way. On the one hand, it is a question of creating a knowledge base in the form of a map, and on the other of defining an abstraction of the system that captures dynamic behaviours of interest. Yet these two constructs share a lot of information, including the mode of influence (e.g., activation or inhibition) and the topology of the network.

In order to bridge the gap between static and dynamic representations, the team has developed CaSQ (CellDesigner as SBML-qual), a tool for automated inference of large Boolean models, from molecular interaction maps based on network topology and semantics.

The large scale Boolean models produced can be simulated and modelled using the Cell Collective modelling platform.

Publications

Singh V, Ostaszewski M, Kalliolias GD, Chiocchia G, Olaso R, Petit-Teixeira E, Helikar T, Niarakis A. Computational Systems Biology Approach for the Study of Rheumatoid Arthritis: From a Molecular Map to a Dynamical Model. Genom Comput Biol. 2018;4(1). pii: e100050. doi: 10.18547/gcb.2018.vol4.iss1.e100050. Epub 2017 Dec 6. PubMed PMID: 29951575.

Development Team

Vidisha Singh Vidisha Singh, MSc
University of Evry, University of Paris-Saclay, France
PhD Student
GenHotel EA3886
European Research Laboratory for Rheumatoid Arthritis, Genopole, Evry
RA-Map and CaSQ development
Sara Sadat Aghamiri Sara Sadat Aghamiri, Msc
University of Evry, University of Paris-Saclay, France
Master student, Department of Biology
GenHotel EA3886
European Research Laboratory for Rheumatoid Arthritis, Genopole, Evry
CaSQ benchmarking
Anna Niarakis Anna Niarakis, PhD
University of Evry, University of Paris-Saclay, France
Associate Professor, Department of Biology
GenHotel EA3886
European Research Laboratory for Rheumatoid Arthritis, Genopole, Evry
RA-Map and CaSQ development
Sylvain Soliman Sylvain Soliman, PhD
Inria Saclay-Île de France, Palaiseau, France
Researcher
CaSQ development
Tomas Helikar Tomas Helikar, PhD
University of Nebraska-Lincoln, Lincoln, NE, USA
Associate Professor, Department of Biochemistry
Cell Collective modelling platform

Editorial Panel

George D. Kalliolias George D. Kalliolias, MD, PhD
Hospital for Special Surgery, Weill Cornell Medical College, New York City, US
Director of Precision Medicine Laboratory at the Hospital for Special Surgery, Assistant Professor of Medicine at the Weill Cornell Medical College
Elisabeth Petit-Teixeira Elisabeth Petit-Teixeira, PhD
University of Evry, University of Paris-Saclay, France
Professor, Department of Biology
GenHotel EA3886
European Research Laboratory for Rheumatoid Arthritis, Genopole, Evry

Former contributors

Gilles Chiocchia Gilles Chiocchia, PhD
University of Versailles-Saint-Quentin-en-Yvelines, France
Professor - Hospital Practitioner
Director INSERM UMR 1173 - Infection and Inflammation
Head of Laboratory of Chronic Infection and Inflammation
Saran Pankaew Saran Pankaew, Msc
University of Evry, University of Paris-Saclay, France
Master student, Department of Biology
GenHotel EA3886
European Research Laboratory for Rheumatoid Arthritis, Genopole, Evry
David Gibson David Gibson, PhD
University of Ulster, UK
Lecturer in Stratified Medicine, School of Biomedical Sciences
Steven Watterson Steven Watterson, MPhys, PhD
University of Ulster, UK
Lecturer in Computational Biology (Hypertension), School of Biomedical Sciences
Andrew Parton Andrew Parton, BSc
University of Ulster, UK
PhD Student

Funding

  • PhD project "Integrative Modelling and Analysis of Molecular Pathways dysregulated in Rheumatoid Arthritis" is funded by the Doctoral School "Structure and Dynamics of Living Systems", the University of Paris-Saclay.
  • CASyM research exchange grant, 2015. Awarded project: “Building a unified pathway theory of inflammation across asthma, rheumatoid arthritis and atherosclerosis”.