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NCM 2022: Ultra-deep targeted transcript sequencing identifies isoform diversity across human pancreatic development


The human pancreas is an incredibly complex organ with multiple functions. There is limited knowledge surrounding the genomic and epigenomic regulation in the development of the pancreas. While some studies have investigated the gene expression levels of the developing pancreas using short-read sequencing, there is a lack of transcript-level assessment to catalogue isoform diversity over time. We used Oxford Nanopore long-read transcriptome sequencing to investigate alternative splicing events in 31 human foetal pancreas samples, spanning 6 to 21 weeks post-conception. Using a targeted approach, we performed ultra-deep sequencing of 330 genes associated with diabetes, neurodevelopmental disorders, and schizophrenia. We identified significant isoform diversity across diabetes-associated genes throughout the development of the pancreas, detecting novel transcripts that were not present in existing gene annotations, including the identification of fusion transcripts utilising exons from adjacent genes. Our long-read transcriptome data indicates the importance of alternative splicing in the developing pancreas, highlighting dynamic changes of transcript isoforms over time. This data also provides a unique resource for understanding the landscape of the transcriptome across pancreatic development.

Authors: Ailsa MacCalman

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