The “GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork” (GEMSTONE)

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Background

Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). On top of the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in case collections has also brought to attention new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is a pressing need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care.

The “GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork” (GEMSTONE) has taken on this challenge, aiming at setting the ground for the:
1) functional characterization of discovered genes and pathways;
2) understanding of the correspondence between molecular and clinical assessments;
3) implementation of novel methodological approaches.
This endeavour is funded by The European Cooperation in Science and Technology (COST), a funding organisation for the creation of research networks.

GEMSTONE embraces five working groups (WG), each with specific objectives:
- WG1-Study populations and expertise groups: aims at creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise.
- WG2-Phenotyping: aims to describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways.
- WG3-Monogenic conditions- human KO models: aims to make an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility.
- WG4 Functional investigations aims at creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system.
- WG5 Bioinformatics seeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications.
- WG6-Translational outreach aims to make a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.

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