Long-read genome sequencing (lrGS) was named Technology of the Year in 2022 for its remarkable ability to nearly complete the sequencing of genomes while addressing significant limitations of current short-read sequencing technologies. These limitations include the omission of 99 genes in the standard reference genome, inadequate coverage of larger repeat expansions, challenges in distinguishing between genes and pseudogenes, difficulties in parental haplotyping/phasing of variants, and the promising potential to identify haplotype-specific epigenetic modifications, such as methylation. Given these advantages, lrGS could potentially establish itself as the gold standard in diagnostics in the near future. This transition is crucial, as approximately 40% of patients with rare diseases remain undiagnosed after short-read genome sequencing, translating to around 15 million patients in Europe and over 150 million worldwide. Similarly, the majority of early and complex cancer syndromes remain unresolved.

In response to this medical need, we aim to further implement innovative technologies to uncover new genetic causes of suspected genetic conditions. Having successfully integrated short-read sequencing in clinical diagnostics for rare diseases and familial cancer syndromes for half a decade, we now seek to harness the full potential of combined complete genome sequencing and initial epigenome data analysis in preparation for its integration as a first-line technology in diagnostic pathways.

This endeavour presents unprecedented challenges for all collaborators, particularly concerning diagnostic standards, data processing and storage, bioinformatics algorithms, data interpretation, and reporting. ELRIN aims to address these challenges by facilitation the knowledge exchange between scientists and clinicians across Europe.