Genome-Phenome Analysis Platform

The RD-Connect Genome-Phenome Analysis Platform is an online tool for diagnosis and gene discovery in rare disease research.

The RD-Connect Genome-Phenome Analysis Platform is an online tool for diagnosis and gene discovery in rare disease research. The user-friendly interface lets users, even without bioinformatic training, analyse Next-Generation Sequencing (NGS) data, such as genomes and exomes, and share them with other researchers. The Platform’s unique features allow identifying disease-causing mutations in rare disease patients and linking them with detailed clinical information (phenotypic data). The service is provided free of charge for authorised scientists and clinicians around the world.

How to use the Genome-Phenome Analysis Platform

The Platform is a rich source of sequencing data thanks to the initial collaboration with research projects NeurOmics and EURenOmics, which submitted hundreds of whole exomes and genomes of patients with rare neuromuscular, neurodegenerative and kidney diseases. The number of cases submitted by researchers is increasing, covering various disease areas.

For latest updates, see the platform release notes and the Platform update in our monthly newsletter.

What you need to know about Genome-Phenome Analysis Platform

A number of inbuilt functionalities allow identifying disease-causing genetic variants in patients and solving even difficult cases.

Basic filters Users can analyse one or multiple individuals, e.g. patient and family members. The results can be filtered by quality, mode of inheritance (e.g. autosomal, homozygous recessive, compound heterozygous, etc.), population frequencies and known and expected pathogenicity according to ClinVar database and several predictors.

Runs of Homozyocity (RoH) allow identifying consanguineous cases even when not identified as such by the clinician. RoH narrows the search down to the homozygous regions in the patient’s genome, which are more likely to be contain the disease-causing variant.

Phenotypic data The Platform matches individuals’ sequencing data with detailed clinical information about his/her symptoms (deep phenotyping), which are stored in the Human Phenotype Ontology (HPO) format in the PhenoTips database. The Platform allows refining the genomic analysis results by selected HPO-encoded symptoms, or genes related to a specific disease in the OMIM (Online Mendelian Inheritance in Man) database.

Built-in Exomiser The fully-integrated Exomiser tool extracts clinical information from PhenoTips automatically and highlights the candidate variants best matching the patient’s symptoms.

Patient matchmaking allows finding individuals with variants affecting the gene of interest. Presence of similar symptoms in the matching patients is a strong hint that a given variant is disease causing and helps confirm genetic diagnosis. Matchmaking can also help basic researchers learn how mutations in the gene they study affect humans.

Connection to other databases To make gene discovery easier, all variants on the results list have direct links to variant descriptions in external databases, such as OMIM, PubMed and Ensembl.

RD-Connect bioinformatic tools In addition, RD-Connect has developed several bioinformatic tools to help researchers analyse omics data and identify targets for potential therapies. Read more >>

All sequencing data are submitted as raw data in FASTQ (or BAM) format and are processed through the same standard pipeline. This ensures that data from different sequencing providers are comparable. The raw data are stored for long-term access at the European Genome-phenome Archive (EGA), a secure, controlled-access repository. The processed data are accessible online for real-time analysis in the RD-Connect Genome-Phenome Analysis Platform.

The European Genome-phenome Archive (EGA) is a repository for all types of sequencing and genotype experiments, including case control, population, and family studies. It includes genotypes regarding single nucleotide polymorphism (SNPs) and copy number variant (CNVs) from array based methods and genotyping done with re-sequencing methods.

The EGA serves as archive for publication as well as data on several levels, including the raw data (so they could be re-analysed in the future using other algorithms) and the genotype calls (information about pathogenic genetic variants) provided by the data submitters.

The EGA provides the necessary security required to control access to the data and maintain patient confidentiality. Data can be viewed only by authorised researchers and clinicians. In all cases, data access decisions are made not by the EGA but by an appropriate Data Access Committee.

RD-Connect pays much attention to the data quality and security and the data in the Platform meet high quality and safety standards.

Who can access the data? The data stored on the Genome-Phenome Analysis Platform can be accessed only by the authorised scientists and clinicians who underwent the registration and verification process. How to register >>

Embargo period The users can analyse and query their own data as well as data submitted by others. Data become accessible to other authorised users only after a predefined embargo period of six months which allows researchers priority to access to their own data.

Patient security and confidentiality To protect patient privacy, data of individual patients are linked to the unique RD-Connect IDs. Patients’ identity data are not stored on the Platform and cannot be accessed by Platform users. Only the researcher, who submitted the data, has the key to identify the IDs corresponding to his/her data. Read more about ethical, legal and social issues >>

A straightforward, secure registration process allows researcher around the world to access the system and carry out research on the Platform free of charge. The process involves authentication of a user as a researcher and signing the adherence agreement. To learn more, see the Genome-Phenome Analysis Platform Registration Guide

Currently, all RD-Connect services are entirely free for all users, as all development and maintenance costs are covered by the European Union’s FP7 scheme.

No. RD-Connect only helps to analyse sequencing data, but does not provide sequencing services.

The Platform has been developed at the Centro Nacional de Análisis Genómico (CNAG) in Barcelona, Spain.