[en] Introduction: 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. Methods: 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+render. 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. Results: We demonstrate the functionality of our workflow on two examples of rare diseases: Kawasaki disease and retinitis pigmentosa. Two maps are constructed based on their corresponding identifiers. Moreover, for the retinitis pigmentosa use-case, we include a list of differentially expressed genes to demonstrate how to tailor the workflow using omics datasets. Discussion: 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 https://gitlab.lcsb.uni.lu/minerva/automap/.
Disciplines :
Biotechnology
Author, co-author :
Gawron, Piotr; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
Hoksza, David; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg ; Faculty of Mathematics and Physics, Charles University, Prague, Czechia
Piñero, Janet; Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain ; Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain ; MedBioinformatics Solutions SL, Barcelona, Spain
Peña-Chilet, Maria; Computational Medicine Platform, Fundacion Progreso y Salud, Sevilla, Spain ; Spanish Network of Research in Rare Diseases (CIBERER), Sevilla, Spain
Esteban-Medina, Marina; Computational Medicine Platform, Fundacion Progreso y Salud, Sevilla, Spain
Fernandez-Rueda, Jose Luis; Computational Medicine Platform, Fundacion Progreso y Salud, Sevilla, Spain
Colonna, Vincenza; Institute of Genetics and Biophysics, National Research Council of Italy, Naples, Rome ; Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
Smula, Ewa; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
HEIRENDT, Laurent ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Ancien, François; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
GROUES, Valentin ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
SATAGOPAM, Venkata ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
SCHNEIDER, Reinhard ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Dopazo, Joaquin; Computational Medicine Platform, Fundacion Progreso y Salud, Sevilla, Spain ; Spanish Network of Research in Rare Diseases (CIBERER), Sevilla, Spain
Furlong, Laura I; Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain ; Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain ; MedBioinformatics Solutions SL, Barcelona, Spain
OSTASZEWSKI, Marek ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
This work was conceptualized and prototyped during the BioHackathon Europe, organized and funded by the ELIXIR Hub in November 2019 in Paris. We thank the organizers for an opportunity to participate in such a productive and collaborative event. We thank Steve Laurie, Centro Nacional de Análisis Genómico (CNAG-CRG), Barcelona, Spain, for support in the domains of rare disease phenotyping and genomics. The work presented in this paper was carried out using the ELIXIR Luxembourg tools and services.
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