Tjakko van Ham from the Erasmus University Medical Center in the Netherlands presented at London Calling 2024. The session was titled “Combined RNAseq and long-read sequencing for unsolved cases.” They began by describing how, in a diagnostic lab, exome sequencing is typically used. However, copy number variants, sequence variants, and non-coding variants may be challenging to detect. van Ham and team modified a method of genome-wide detection of abnormal pre-mRNA splicing and RNA expression. They tested this method with seventy patient samples and improved the method of cell culture, and designed a web browser application for RNA-seq analysis. van Ham described an example of RNAseq analysis that was necessary to identify a variant in MFSD8: a splice enhancer that is typically challenging to predict. The team is exploring nanopore sequencing for several research applications. In another case, transcriptome analysis helped identify a TCOF1 transcript isoform switch that may be related to Treacher-Collins syndrome. van Ham shared several additional examples of how nanopore sequencing helped reveal abnormal regions and transcripts that help improve understanding of rare diseases. I would like to learn more about their approach and bioinformatics web application. It seems they take samples and grow fibroblasts for expression studies. Also, the software is web-based!
