Periodic report RP3

Periodic report RP3

The Solve-RD periodic report for the third reporting period has just been submitted.

In the last 18 months (from 01/2021 to 06/2022), we continued to implement the activities addressing the three challenges (see here).

We reached our goal and collected 21,348 datasets (phenotypic & exome/genome sequencing data) from unsolved RD patients and their family members. Standardised phenotypic information (HPO, ORDO & OMIM encoded) has been collected via the RD-Connect GPAP PhenoStore module.

We have continued producing and enriching the Rare Disease Case Ontology (RDCO). Up to now, RDCO has been populated with 412,500 similarity associations.

Re-analysis of data freezes 1 & 2 has been done by the Data Analysis Task Force DATF working groups. Results have been prioritized and interpreted by the Data Interpretation Task Forces (DITFs) of each ERN. This collaborative effort led to the diagnosis of 511 patients from 6,003 families. This is already an 8.5 % additional diagnostic rate although many of the analyses and evaluations are still ongoing. The new re-analysis approach pursued in Solve-RD as well as the structures we established to warrant best exchange of expertise have been published in a series of papers in the EJHG in June 2021.

Service providers have been chosen for all novel omics technologies. SOPs for biomaterials have been shared with all ERN partners via the DITFs. Sample shipment is only slowly progressing; however, >3,000 samples have been sent to the central lab in Nijmegen for QC and then further distributed to the respective service providers.

The RDMM-Europe brokerage service connecting Solve-RD partners who discovered novel RD genes with model organism scientists that have the expertise to functionally validate these genes and variants opened 10 calls for Connection Applications. 36 Seeding Grants have been awarded so far.

The co-designed models for the communication of genomic results for RD have been published (Costa et al.). The main finding at both study sites in the Czech Republic and the UK was the identification of post-test care as the shared priority for improvement for both health professionals and families.

The conference ECOgenomics “European Conference on the Diffusion of Genomic Medicine: Health Economics & Policy” took place online from 26-28 May 2021. Plenary sessions and parallel thematic sessions brought together researchers from the human sciences (mainly health economics), but also researchers from other disciplines.

The Treatabolome database has been released and an API connects it to the RD-Connect GPAP to make information about treatable genes and variants of RDs accessible and to improve the visibility of existing variant-specific treatment options at the time of diagnosis to clinicians and their patients. It includes data from 10 systematic literature reviews of which six have been published in a special issue in May 2021 in the JND.

The data flow system has continuously been adapted to the project’s needs involving GPAP, the EGA, omics service providers, the sandbox and RD3. GPAP’s new Cohort App module facilitates the exploration and construction of cohorts on experiments metadata and structured clinical data using standard ontologies to improve the analysis of defined cohorts. The FUSE client enables access to files stored at the EGA via the Sandbox and also for real-time visualisation in a genome browser like IGV when analysing data in the GPAP.