Speaker: Dr Lauren McIntyre, Professor in Molecular genetics & Microbiology at the University of Florida.
Title: “Quantifying Alternative Splicing”
Abstract: Many eukaryotic genes are transcribed into multiple mRNAs through alternative splicing (AS) leading to differing functional properties and/or encoded proteins from the same gene . This differential processing has been hypothesized to be a primary mechanism of protein diversity in a variety of eukaryotes. Dramatic differences in splicing events among tissues, environments, cell types, and developmental stages within a single species are well documented across the tree of life. We develop a mathematical framework to calculate complexity and compare transcript models. Structural features, i.e. intron retention (IR), donor/acceptor site variation, alternative exon cassettes, alternative 5′/3′ UTRs, are compared and the distance between transcript models is calculated with nucleotide level precision. Distance metrics can be used to summarize splicing patterns for a transcriptome (1GTF) and between transcriptomes (2GTF). We show how this is useful in comparing alternate annotations for a species (e.g. RefSeq vs Ensembl). We also who how describing splicing patterns can lead to interesting observations about transcription across the tree of life. Sex-determination in Drosophila is the classic example of an alternative splicing cascade. We have observed that sex-bias of gene expression in adult heads is pervasive and can be conserved between sister-species D. melanogaster and D. simulans. We hypothesize this may be due to sex-specific splicing and examine this hypothesis with long-read RNA-seq data. We use distance metrics to pinpoint structural differences in sex-biased transcripts.
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