It’s a privilege to announce Solve-RD’s latest manuscript based on years of work: “Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses”
https://lnkd.in/eMqdDsQX
A thread (1/n)
This pan-European data re-analysis involved a massive effort by so many! With the gratifying result to allow a diagnosis in >500 of >6,000 previously undiagnosed rare disease (RD) patients and families. (2/n)
Some of the main lessons: solve-RD brought together:
- Data: data sharing works across all of Europe across all different systems and legislations.
- RD expertise: >300 experts: colleagues, collaborators and friends. (3/n)
- re-analysis of even very heterogeneous datasets can be successful. The ever growing toolset, as well as knowledge about genes and variants makes existing data extremely valuable. This pan-continental effort replicates massive national efforts. (4/n)
- coding SNVs/InDels were classified as (likely) disease causing now, because a) same variant was identified and classified as pathogenic in meantime (eg ClinVar); (5/n)
b) the disease gene was only recently described; c) the variant was new/private but Solve-RD allowed a consensus of two-level-expert review (data analysis and data interpretation experts) (6/n)
- a significant proportion of cases were diagnosed thanks to “non-standard variant types” that were newly called by latest tools: CNVs, SVs, MEI, STR, mtDNA, deep-intrinsic splice sites (7/n)
- Additional candidates and ad hoc diagnoses also shared here (n=333 & n=249)
- Of all newly identified RD diagnoses, >14% are “actionable” with today’s knowledge. (8/n)
- All data is available to the global RD community. Raw data via EGA; annotated and searchable data via RD-connect (which if continue to filled with similar efforts may become the “GnomAD of RD”) (9/n)
- Here we offer a practical and pragmatic blueprint for even larger RD data sharing initiatives. This is scalable (here 10k datasets; within Solve-RD now 20k), and will be scaled-up eg in ERDERA (>100k). (10/n)
Read the manuscript. (OA!), and its massive supplement - much more to discover - and let us know how to engage in future efforts. (11/11).
Importantly; many people to thank: The biggest success factor was trust and engagement: collaboration, collaboration, collaboration.
We are very grateful to all families and patients that allowed this partnership. We also thank the EU for Solve-RDs funding, as well as all other funders.
All ERN partners particularly ERN GENTURIS ERN-NMD, ERN-RND, & ITHACA.
Many thanks to the entire Solve-RD consortium; with special shoutout to our fantastic coordinating office in Tübingen Holm Graessner
Likewise all DATF and DITF leads and members. And so many other fantastic colleagues that all agreed to jointly engage in this effort.
In particular all joint co-first and co-last authors! Steve Laurie Sergi Beltran Agulló Elke de Boer Lisenka Vissers Richarda de Voer Wouter Steyaert & many!
