Splicing and Junction Mapping

High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as ...

The vast majority of multi-exon genes in humans undergo alternative splicing, which greatly increases the functional diversity of protein species. Predicting functions at the isoform level is essential to further our understanding of developmental abnormalities and cancers, which frequently exhibit ...

Gustavo Sacomoto In this thesis, we address the problem of identifying and quantifying variants (alternative splicing and genomic polymorphism) in RNA-seq data when no reference genome is available, without assembling the full transcripts. Based on the fundamental idea that each ...

The computational prediction of alternative splicing from high-throughput sequencing data is inherently difficult and necessitates robust statistical measures because the differential splicing signal is overlaid by influencing factors such as gene expression differences and simultaneous expression of multiple isoforms amongst ...

Several state-of-the-art methods for isoform identification and quantification are based on l1-regularized regression, such as the Lasso. However, explicitly listing the-possibly exponentially-large set of candidate transcripts is intractable for genes with many exons. For this reason, existing approaches using the ...

Ultrahigh-throughput sequencing of cDNA (RNA-Seq) is an invaluable resource for investigating alternative splicing in an organism. Alternative splicing is a form of posttranscriptional regulation in which primary RNA transcripts from a single gene can be spliced in multiple ways leading ...

The vast majority of multi-exon genes in higher eukaryotes are alternatively spliced and changes in alternative splicing (AS) can impact gene function or cause disease. High-throughput RNA sequencing (RNA-seq) has become a powerful technology for transcriptome-wide analysis of AS, but ...

Interpretation of variants present in complete genomes or exomes reveals numerous sequence changes, only a fraction of which are likely to be pathogenic. Mutations have been traditionally inferred from allele frequencies and inheritance patterns in such data. Variants predicted to ...

Advantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs) and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. Researchers at the Mayo Clinic ...

The identification of gene fusions promises to play an important role in personalized cancer treatment decisions. Many rare gene fusion events have been identified in fresh frozen solid tumors from common cancers employing next-generation sequencing technology. However the ability to ...