Rare Disease Service Bundle – Assessing Molecular Pathogenicity for Rare Diseases (AMP4RD)
Creators: name: Capriotti, Emidio
name: Salgado, David
name: Agullo, Sergi Beltran
name: Casadio, Rita
name: Facchiano, Angelo
name: Licata, Luana
name: Marabotti, Anna
name: Martelli, Pier Luigi
name: Borrel, Lesley Matalogna
name: Millan, Pablo Porras
name: Saunders, Gary
name: Castrense Savojardo
name: Tartari Giacomo
Publisher: name: F1000 Research Limited
Year: 2020

description: Service Bundle (SB) is a new mechanism to identify how ELIXIR platforms and communities are able to address specific user needs that are not directly satisfied by the current infrastructures offered by ELIXIR.<br>We have implemented a proposal for a Rare Disease Service Bundle (AMP4RD) to define procedures and guidelines for the annotation and interpretation of the genetic variants in the human genome. Our initiative aims to implement an integrated infrastructure for characterizing the relationship between genotype and phenotype both from the clinical and research perspectives.<br><br><b>AMP4RD</b><br>This poster presents the adopted strategy to identify the services provided by the ELIXIR platforms and communities that are essential for the implementation of this Service Bundle. We will describe how the Service Bundle team has been able to pinpoint the valuable tools, resources and datasets required for the annotation and interpretation of the genetic variants in the context of Rare Diseases (RD). <br>This poster is a also a conversation starter, allowing the RD Service Bundle team to collect feedback on the proposed solution and to eventually expand the current proposal with new tools and resources.<br><br><b>Use Cases</b><br>Within ELIXIR the AMP4RD Service Bundle focuses on specific scientific domains related to the study of genes, proteins and their interactions. The SB identifies the ELIXIR core data resources for delivering computing workflows and tools for the annotation and interpretation of the genetic variants (Fig. 1). <br>In detail our initiative aims to integrate 3 main use cases: Identify supporting evidences to define genotype-phenotype relationships. Characterize the molecular mechanisms underlying genetic diseases. Predict the impact of genetic variations on protein structure and function. <b>Tools &amp; Workflows</b><br>According to the use cases described above we defined two workflows for: Generating a disease report starting from DNAseq data. Predict di impact of genetic variants at protein level. For the practical implementation of the workflows we collected a set of resources and tools already included in the ELIXIR bio.tools registry for addressing each task. In the first workflow (Fig. 2) we focus initially on the annotation and interpretation of the small variants (SNV and indels) for identifying a set of “actionable” variants. In this context, we defined a specific workflow for predicting the impact of the genetic variants at protein level using structural and functional information (Fig. 3).<br>Furthermore our Service Bundle is collecting a pool of ELIXIR and external training activities to familiarize scientist from different research fields with the state-of-the-art resource and tools for variant interpretation.<br>Currently we are working on the organization of a BioHackaton in collaboration with the colleagues of the workflow community. This initiative constitutes a first step toward the generation of computing workflows for addressing the tasks represented in the two charts mentioned above.