Responsible and Reproducible Research

Visualization of automatically combined disease maps and pathway diagrams for rare diseases#

Piotr Gawron, David Hoksza, Janet Piñero, Maria Pena Chilet, Marina Esteban, Jose Luis Fernandez-Rueda,Vincenza Colonna, Ewa Smula, Laurent Heirendt, François Ancien, Valentin Groues, Venkata Pardhasaradhi Satagopam, Reinhard Schneider, Joaquin Dopazo, Laura I. Furlong, Marek Ostaszewski

Investigation of molecular mechanisms of human disorders, especially rare diseases, require exploration of various knowledge repositories for building precise hypotheses and complex data interpretation. Recently, increasingly more resources offer diagrammatic representation of such mechanisms, including disease-dedicated schematics in pathway databases and disease maps. However, collection of knowledge across them is challenging, especially for research projects with limited manpower. In this article we present an automated workflow for construction of maps of molecular mechanisms for rare diseases. The workflow requires a standardized definition of a disease using OrphaNet or HPO identifiers to collect relevant genes and variants, and to assemble a functional, visual repository of related mechanisms, including data overlays. The diagrams composing the final map are unified to a common systems biology format from CellDesigner SBML, GPML and SBML+layout+renders. The constructed resource contains disease-relevant genes and variants as data overlays for immediate visual exploration, including embedded genetic variant browser and protein structure viewer. We demonstrate the functionality of our workflow on an example of Kawasaki disease. In summary, our work allows for an ad-hoc construction of molecular diagrams combined from different sources, preserving their layout and graphical style, but integrating them into a single resource. This allows to reduce time consuming tasks of prototyping of a molecular disease map, enabling visual exploration, hypothesis building, data visualization and further refinement. The code of the workflow is open and accessible at

Raw data#

The datasets are available at, MINERVA exports adhoc_ORPHA2331 and adhoc_ORPHA791.

Source code#

The scripts used to analyse the data are available from GitLab.

Web service#

A workflow to create the disease map on the file is available under