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Open Challenge

The RAS-RAF-MEK-ERK Pathway Challenge

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Project description

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.

In preparation for this challenge, the RAS-RAF-MEK-ERK components in the following resources have been analysed: the Atlas of Cancer Signalling Network, the Reactome database and PANTHER database (Briefings in Bioinformatics doi: 10.1093/bib/bbab103). We plan to build on this experience, further explore the existing versions of the pathway, develop missing pieces from scratch and create an integrated consensus map, with multiple variants for different conditions and cell types.

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.


  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 working with this example, develop clear guidelines and specific solutions for creating composable components and assembling them into modular maps.

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.

Please use this self-organised form by 10 April 2021 to express your interest.

Kickoff events

Virtual kickoff meetings are scheduled for 15th April 2021 at 10:00 UTC and at 16:00 UTC to accommodate different time zones. Please join via Webex using this link.


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 30 September 2021.


The results of this work will be distributed under the Creative Commons Public Domain (CC0) License: all pathway diagrams and pathway files with the corresponding annotation information.


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