ASCOT preprint

Jonathan Ling, together with Langmead lab members Chris Wilks and Rone Charles and collaborator Seth Blackshaw, posted a preprint describing ASCOT ( The preprint is available at: ASCOT a new resource — building on the Snaptron ( tool and resource — allowing researchers to visualize and query alternative splicing patterns in public RNA-Seq data. ASCOT enables rapid identification of splice-variants across tens of thousands of bulk and single cell RNA-Seq datasets in human and mouse. To demonstrate the utility of ASCOT, we identified many alternative exons used only by a single neuronal subtype. We then leveraged datasets from the ENCODE and GTEx consortiums to study the unique splicing patterns of rod photoreceptors and found that PTBP1 knockdown combined with overexpression of MSI1 and PCBP2 activates rod-specific exons in HepG2 liver cancer cells. Furthermore, we observed that MSI1 targets intronic UAG motifs proximal to the 5′ splice site and interacts synergistically with PTBP1 downregulation. Finally, we show that knockdown of MSI1 in the retina abolishes rod-specific splicing. This work demonstrates how large-scale analysis of public RNA-Seq datasets can yield key insights into cell type-specific control of RNA splicing and underscores the importance of considering both annotated and unannotated splicing events.


Published:December 20, 2018


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