Matthew Bainbridge from the Rady Children’s Institute for Genomic Medicine in the US spoke at the Nanopore Community Meeting in Boston. The session was titled “Long-read sequencing for detecting methylation dysregulation.” Bainbridge noted that they see almost 250,000 children a year and are the only children’s hospital in Riverside County. Most of the children they see have neurologic disorders. Bainbridge The Rady Longread Cohort had 55 probands, 52 pediatric cases, and 3 adults. Eleven had known molecular findings. Repeat expansion was defined as short repetitive unit that gets longer with each generation going from dozens of baes to hundreds or thousands… and disease severity and onset are related to length. Case studies with DMPK repeats were described. Short reads could not accurately define repeat total length. Long-read sequencing identified total expansion. In another case, Bainbridge spoke about an R953 mosaic duplication case that was phased despite parental information being unavailable. A third case was a 1 day-old male with a complex cardiac phenotype. The baby had a pattern of malformation of chromosome rings. With long-read sequencing, the variant callers identified the ring/inversion correctly. Bainbridge spoke about methylation and imprinting next. They shared cases in which methylation dysregulation was detected. They applied a window and identified dysregulated methylation regions. Bainbridge shared a comparison of PacBio, short read, and ONT analyses of some of these samples, noting that while there is overlap in many methylated genes, some are only identified with PacBio and/or ONT. Bainbridge concluded that more studies are needed to continue learning which approach is most appropriate for different clinical scenarios.
