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Open Challenge

The RAS-RAF-MEK-ERK Pathway Challenge

Get involved
Anticipated sub-modules


The RAS-RAF-MEK-ERK Pathway Challenge is an open project that aims at employing reusability and composability as design principles for assembling extensive Process Description maps and for enabling efficient large-scale collaborative efforts. We would like to progress through working with a specific example, the RAS-RAF-MEK-ERK signalling, and develop the most up-to-date version of this signalling cascade so it can be used as a reference resource.

The RAS-RAF-MEK-ERK components in the following resources have been analysed: the Atlas of Cancer Signalling Network, the Reactome databases and PANTHER database (preprint available at https://doi.org/10.1101/2020.12.08.416719).

Get involved

All researchers interested in this topic are invited to contribute. We encourage students and young researchers to participate. There are many interesting tasks including reviewing pathway databases, reviewing the literature and developing pathway diagrams.

We would be grateful for help from experts on the topic of RAS-RAF-MEK-ERK signalling and experienced curators who are interested in working with students and young researchers to develop maps of this signalling cascade.

Please use this self-organised form by 31 March 2021 to express your interest. With questions and suggestions, please contact organisers at openchallenge@googlegroups.com.


Modularity and composability are desired features of network components that we believe would simplify the construction and composition of biochemical maps. Focusing on a specific example that is feasible to review, analyse and maintain, we would like to employ advanced design principles that could enable large collaborative efforts to build comprehensive biochemical maps.

The RAS-RAF-MEK-ERK signalling cascade is part of many pathway maps, and when developing a new map it is not always clear whether the RAS-RAF-MEK-ERK cascade should be developed from scratch based on recent literature or it is possible to reuse available reconstructions of the cascade. For the already existing representations, it takes time and resources to find and extract relevant fragments from pathway databases, and it is often not clear which one is the best version to reuse.


  1. Design a minimal set of pathway variants of the RAS-RAF-MEK-ERK cascade that can be applied in a composable manner for developing larger maps.
  2. Using the experience of developing this example, develop clear guidelines and specific solutions for creating composable components and assembling them into modular maps.

Anticipated sub-modules

Specific mechanisms will be identified and reviewed during this project. We anticipate that sub-modules will be designed according to different RAF proteins such as RAF1, BRAF and ARAF, and scaffold and adaptor proteins such as KSR1, SEF-1, CNK1, IQGAP1, PHB, MORG1 and others as regulators of ERK activity or spatial regulators of the pathway.


We will form working groups and distribute tasks in April 2021. Work on the challenge will be conducted in the Spring and Summer of 2021. We plan to summarise and present the results of the challenge by 31 August 2021.


Alexander Mazein, Luxembourg Centre for Systems Biomedicine, Belval, Luxembourg
Adrien Rougny, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
Jonathan Karr, Icahn School of Medicine at Mount Sinai, New York, USA
Julio Saez Rodriguez, Heidelberg University Hospital, Heidelberg, Germany
Marek Ostaszewski, Luxembourg Centre for Systems Biomedicine, Belval, Luxembourg
Inna Kuperstein, Institut Curie, Paris, France
Andrei Zinoviev, Institut Curie, Paris, France
Anna Niarakis, University of Evry, University of Paris-Saclay, Evry, France
Reinhard Schneider, Luxembourg Centre for Systems Biomedicine, Belval, Luxembourg