compatibility; composability; modularity; process description; quality verification; reusability; systems biology; raf Kinases; ras Proteins; Computational Biology/methods; Data Mining/methods; Humans; Internet; Models, Biological; Neoplasms/metabolism; Phosphorylation; Reproducibility of Results; raf Kinases/metabolism; ras Proteins/metabolism; Databases, Factual; MAP Kinase Signaling System; Computational Biology; Data Mining; Neoplasms; Information Systems; Molecular Biology
Abstract :
[en] 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.
Disciplines :
Biotechnology
Author, co-author :
MAZEIN, Alexander ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core ; European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Université de Lyon, 50 Avenue Tony Garnier, 69007 Lyon, France
Rougny, Adrien; Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Aomi, Tokyo, Japan ; Com. Bio Big Data Open Innovation Lab. (CBBD-OIL), AIST, Aomi, Tokyo, Japan
Karr, Jonathan R; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA ; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
Saez-Rodriguez, Julio; Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, 52074 Aachen, Germany ; Institute for Computational Biomedicine, Heidelberg University Hospital and Heidelberg University, Faculty of Medicine, Bioquant Heidelberg, Heidelberg 69120, Germany
OSTASZEWSKI, Marek ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
SCHNEIDER, Reinhard ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
External co-authors :
yes
Language :
English
Title :
Reusability and composability in process description maps: RAS-RAF-MEK-ERK signalling.
Mazein A, Ostaszewski M, Kuperstein I, et al. Systems medicine disease maps: community-driven comprehensive representation of disease mechanisms. Npj Syst Biol Appl 2018;4:1-10.
Ostaszewski M, Gebel S, Kuperstein I, et al. Communitydriven roadmap for integrated disease maps. Brief Bioinform 2019;20:659-670.
Monraz Gomez LC, Kondratova M, Ravel J-M, et al. Application of Atlas of Cancer Signalling Network in preclinical studies. Brief Bioinform 2019;20:701-16.
Ravel J-M, Monraz Gomez LC, Sompairac N, et al. Comprehensive map of the regulated cell death signaling network: a powerful analytical tool for studying diseases. Cancer 2020;12:990.
Jdey W, Thierry S, Russo C, et al. Drug-driven synthetic lethality: bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors. Clin Cancer Res Off J Am Assoc Cancer Res 2016;23:1001-1011.
Kuperstein I, Grieco L, Cohen DPA, et al. The shortest path is not the one you know: application of biological network resources in precision oncology research. Mutagenesis 2015;30:191-204.
Chanrion M, Kuperstein I, Barrière C, et al. Concomitant Notch activation and p53 deletion trigger epithelial-tomesenchymal transition and metastasis in mouse gut. Nat Commun 2014;5:5005.
Cooling MT, Nickerson DP, Nielsen PMF, et al. Modular modelling with Physiome standards. J Physiol 2016;594:6817-31.
Ostaszewski M, Mazein A, Gillespie ME, et al. COVID-19 disease map, building a computational repository of SARS-CoV- 2 virus-host interaction mechanisms. Sci. Data 2020;7:136.
Degirmenci U, Wang M, Hu J. Targeting aberrant RAS/RAF/MEK/ERK signaling for cancer therapy. Cell 2020;9:198.
Yaeger R, Corcoran RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov 2019;9:329-41.
Yuan J, Dong X, Yap J, et al. The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy. J Hematol Oncol J Hematol Oncol 2020;13:113.
Guo Y-J, Pan W-W, Liu S-B, et al. ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med 2020;19:1997-2007.
Muta Y, Matsuda M, Imajo M. Divergent dynamics and functions of ERK MAP kinase signaling in development, homeostasis and cancer: lessons from f luorescent bioimaging. Cancer 2019;11(4):513.
Lake D, Corrêa SAL, Müller J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci CMLS 2016;73:4397-413.
Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nat Rev Mol Cell Biol 2011;12:104-17.
Rougny A, Touré V, Moodie S, et al. Systems biology graphical notation: process description language level 1 version 2.0. J Integr Bioinform 2019;16(2):20190022.
Le Novère N, Hucka M, Mi H, et al. The systems biology graphical notation. Nat Biotechnol 2009;27:735-41.
Kuperstein I, Bonnet E, Nguyen H-A, et al. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps. Oncogene 2015;4:e160.
Mi H, Muruganujan A, Ebert D, et al. PANTHER version 14: more genomes, a newPANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res 2019;47: D419-26.
Jassal B, Matthews L, Viteri G, et al. The reactome pathway knowledgebase. Nucleic Acids Res 2020;48: D498-503.
Fabregat A, Korninger F, Viteri G, et al. Reactome graph database: efficient access to complex pathway data. PLoS Comput Biol 2018;14:e1005968.
Torii S, Kusakabe M, Yamamoto T, et al. Sef is a spatial regulator for Ras/MAP kinase signaling. Dev Cell 2004;7: 33-44.
