Reusability and composability in process description maps: RAS–RAF–MEK–ERK signalling

Author:

Mazein Alexander12,Rougny Adrien34,Karr Jonathan R56,Saez-Rodriguez Julio78,Ostaszewski Marek1,Schneider Reinhard1

Affiliation:

1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg

2. European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Université de Lyon, 50 Avenue Tony Garnier, 69007 Lyon, France

3. Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Aomi, Tokyo, Japan

4. Com. Bio Big Data Open Innovation Lab. (CBBD-OIL), AIST, Aomi, Tokyo, Japan

5. Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA

6. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA

7. Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, 52074 Aachen, Germany

8. Institute for Computational Biomedicine, Heidelberg University Hospital and Heidelberg University, Faculty of Medicine, Bioquant Heidelberg, Heidelberg 69120, Germany

Abstract

Abstract Detailed maps of the molecular basis of the disease are powerful tools for interpreting data and building predictive models. Modularity and composability are considered necessary network features for large-scale collaborative efforts to build comprehensive molecular descriptions of disease mechanisms. An effective way to create and manage large systems is to compose multiple subsystems. Composable network components could effectively harness the contributions of many individuals and enable teams to seamlessly assemble many individual components into comprehensive maps. We examine manually built versions of the RAS–RAF–MEK–ERK cascade from the Atlas of Cancer Signalling Network, PANTHER and Reactome databases and review them in terms of their reusability and composability for assembling new disease models. We identify design principles for managing complex systems that could make it easier for investigators to share and reuse network components. We demonstrate the main challenges including incompatible levels of detail and ambiguous representation of complexes and highlight the need to address these challenges.

Funder

Innovative Medicines Initiative Joint Undertaking

European Union’s Seventh Framework Programme

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

Reference23 articles.

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