Clinical Interpretation of Variants from Next-Generation Sequencing: The 2016 Scientific Meeting of the Human Genome Variation Society.

The 2016 scientific meeting of the Human Genome Variation Society (HGVS; http://www.hgvs.org) was held on the 20th of May in Barcelona, Spain, with the theme of "Clinical Interpretation of Variants from Next-Generation Sequencing.

Sequence chromatograms of the 4 mutations identified in the gene in this study

<p><b>Copyright information:</b></p><p>Taken from "Trichloroethylene exposure and somatic mutations of the gene in patients with Renal Cell Carcinoma"</p><p>http://www.occup-med.com/content/2/1/13</p><p>Journal of Occupational Medicine and Toxicology (London, England) 2007;2():13-13.</p><p>Published online 12 Nov 2007</p><p>PMCID:PMC2211482.</p><p></p> R and T are DNA from a commercially available reference and tumour tissue tested respectively. Panels A, B and C correspond to 3 different renal clear cell tumours fixed in formalin solution, whereas panel D corresponds to one of the frozen tumours

RD-Connect: an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research

<p><strong>Abstract:</strong></p> <p>Despite many examples of excellent practice, rare disease (RD) research is still frequently fragmented by data type and disease. Individual efforts often have little interoperability and almost no systematic connection of detailed clinical information with genetic information, biomaterial availability or research/trial datasets. Linking data at both an individual-patient and whole-cohort level enables researchers to gain a better overview of their disease of interest, while providing access to data from other research groups in a secure fashion allows researchers in multiple institutions to compare results and gain new insights. Funded by the EU Seventh Framework Programme under the International Rare Diseases Research Consortium (IRDiRC), RD-Connect is a global infrastructure project which links databases, registries, biobanks and clinical bioinformatics data used in RD research into a central research resource. RD-Connect’s primary objectives are:</p> <p>• Harmonisation and development of common standards for RD patient registries by developing a common registry infrastructure and data elements</p> <p>• Harmonisation and development of common standards and catalogue for RD biobanks that collect and provide standardised, quality-controlled biomaterials for translational research</p> <p>• Development of clinical bioinformatics tools for analysis and integration of molecular and clinical data to discover new disease genes, pathways and therapeutic targets</p> <p>• Development of an integrated platform to host and analyse data from omics research projects</p> <p>• Development of mechanisms for incorporating patient interests and engaging with stakeholders</p> <p>• Development of best ethical practices and a proposal for a regulatory framework for linking medical and personal data related to RD.</p> <p>RD-Connect will accept data generated by IRDiRC projects such as EURenOmics, which focuses on causes, diagnostics, biomarkers and disease models for rare kidney disorders, and Neuromics, which uses next generation whole exome sequencing to increase genetic knowledge of rare neurodegenerative and neuromuscular disorders. The “siloed” nature of individual research efforts is a continued bottleneck for cutting-edge research towards diagnosis and therapy development in RD. RD-Connect aims to unite existing infrastructures and integrate the latest tools in order to create a comprehensive combined omics data, biobanking, data analysis and patient registry platform for RD used by researchers across the world.</p

RD-Connect: first year review

<p>In its first year of operation, RD-Connect has successfully achieved its objectives for the period and has begun to establish its position as an important part of the global rare disease research infrastructure. Owing to the need to integrate with existing initiatives, the primary focus of the year has been on ensuring that RD-Connect activities are fully aligned with the needs of the associated projects that will submit data to the system, and on developing interoperability with related tools and projects operating in the same area.<br>Achievements include:<br>• Established strong collaborations with EURenOmics and Neuromics<br>• Incorporation of new associated partners involved in related work<br>• Representation on IRDiRC Scientific Committees and working groups has helped ensure harmonisation with IRDiRC activities<br>• The foundations for the integrated platform have been put in place, ensuring interoperability with other systems and meeting the requirements of IRDiRC projects generating omics data that will be linked with RD-Connect<br>• The first set of data from NeurOmics and EURenOmics will be uploaded in early 2014 after which time data from other IRDiRC projects may be accepted<br>• Various suites of clinical bioinformatics tools to extract knowledge from high throughput experiments, clinical databases and biobanks are being developed<br>• Extensive engagement with ontology developers and the associated projects has ensured that the submitted omics data will be accompanied by standardised phenotypic descriptions using HPO<br>• An extensive mapping exercise carried out jointly with the registry and biobanking WP has resulted in a list of patient registries and biobanks that will now be surveyed to establish their research focus, utility for research and invited to participate in RD-Connect activities<br>• Progress in evaluating the various options to implement a globally unique identifier<br>• Progress towards the development of the biobank catalogue, database structure and biobanking standards<br>• Proactive engagement with the ethical issues raised by omics experiments and patient data sharing<br>• Draft charter with principles and template for sharing and access to data</p> <p> </p

Standardized analysis and sharing of genome-phenome data for neuromuscular and rare disease research through the RD-Connect platform

<b>Abstract: </b><div>RD-Connect (rd-connect.eu) is an EU-funded project building an integrated platform to narrow the gaps in rare disease research, where patient populations, clinical expertise and research communities are small in number and highly fragmented. Guided by the needs of rare disease researchers and with neuromuscular and neurodegenerative researchers as its original collaborators, the RD-Connect platform securely integrates multiple types of omics data (genomics, proteomics and transcriptomics) with biosample and clinical information – at the level of an individual patient, a family or a whole cohort, providing not only a centralized data repository but also a sophisticated and user-friendly online analysis system. Whole-genome, exome or gene panel NGS datasets from individuals with rare diseases and family members are deposited at the European Genome-phenome Archive, a longstanding archiving system designed for long-term storage of these large datasets. The raw data is then processed by RD-Connect's standardised analysis and annotation pipeline to make data from different sequencing providers more comparable. The corresponding clinical information from each individual is recorded in a connected PhenoTips instance, a software solution that simplifies the capture of clinical data using the Human Phenotype Ontology, OMIM and Orpha codes. The results are made available to authorised users through the highly configurable online platform (platform.rd-connect.eu), which runs on a Hadoop cluster and uses ElasticSearch – technologies designed to handle big data at high speeds. The user-friendly interface enables filtering and prioritization of variants using the most common quality, genomic location, effect, pathogenicity and population frequency annotations, enabling users from clinical labs without extensive bioinformatics support to do their primary genomic analysis of their own patients online and compare them with other submitted cohorts. Additional tools, such as Exomiser, DiseaseCard, Alamut Functional Annotation (ALFA) and UMD Predictor (umd-predictor.eu) are integrated at several levels. The RD-Connect platform is designed to enable data sharing at various levels depending on user permissions. At the most basic level (“does this specific variant exist in any individual in this cohort?”) it has lit a Beacon within the Global Alliance for Genomics and Health’s Beacon Network (www.beacon-network.org). At the next stage of sharing – finding similarities between patients in different databases with a matching phenotype and a candidate variant in the same gene – it is actively involved in the development of Matchmaker Exchange (www.matchmakerexchange.org), allowing users of different systems to securely exchange information to find confirmatory cases. And finally, since all patients within the system have been consented for data sharing, users of the system, after validation and authorization, are able to access datasets from other centres, providing an instant means of gathering cohorts for cross-validation and further study. Although open to any rare disease, the platform is currently enriched for neuromuscular and neurodegenerative phenotypes and includes almost 1000 genomic datasets from the NeurOmics project (www.rd-neuromics.eu) with several other contributions in the pipeline, including 1000 limb-girdle muscular dystrophy index cases from the Myo-Seq project (www.myo-seq.org) and more. The platform is free of charge to use and is open for contributions of NGS and phenotypic data from research labs worldwide via [email protected] <p></p></div