The London Calling 2024 session I watched tonight was titled “Long-read sequencing for pathogenic and novel variation discovery in rare diseases.” Ahmad Abou Tayoun from the Al Jailila Children’s Specialty Hospital in the United Arab Emirates was the presenter. This session was part of the Clinical & Biopharma Day on Friday, May 24, 2024. They spoke about the diagnostic yield: the proportion of patients receiving an answer, is around 30-40% with short read sequencing! Long-read sequencing provides information about genomic and epigenomic changes. Abou Tayoun and team conducted a study with a cohort of fifty-three patients with complex diseases. They then applied the knowledge learned to other cohorts. The team developed an in-house optimized protocol to capture genomic and epigenomic changes in a single assay. The method is not the most sensitive, but it has been fine-tuned for the diseases represented by this cohort. The cohort is composed largely of Arab patients, and the N50 obtained was 12 kb with 30X coverage. Several case studies highlighted how the sequencing information helped obtain a diagnosis. The team also performed transcriptomic analyses that helped confirm or support some diagnoses. Droplet digital PCR was used to confirm some of the phenotypes. While their study is under review in Nature, a larger study found similar diagnostic yields with PacBio long-read sequencing. Abou Tayoun concluded by thanking the bioinformatics specialist who developed the pipeline and the patients who consented to participate in the study. I am intrigued by how different long-read technologies produce similar gains in diagnostic yield!
