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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data, Coby Viner, Stephanie Dorman, Ben Shirley, Peter Rogan
Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data, Coby Viner, Stephanie Dorman, Ben Shirley, Peter Rogan
Biochemistry Publications
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 alter mRNA splicing can be validated by manual inspection of transcriptome sequencing data, however this approach is intractable for large datasets. These abnormal mRNA splicing patterns are characterized by reads demonstrating either exon skipping, cryptic splice site use, and high levels of intron inclusion, or combinations of these properties. We present, Veridical, an in silico method for the automatic validation …
Splicing Mutation Analysis Reveals Previously Unrecognized Pathways In Lymph Node-Invasive Breast Cancer., Stephanie N Dorman, Coby Viner, Peter K Rogan
Splicing Mutation Analysis Reveals Previously Unrecognized Pathways In Lymph Node-Invasive Breast Cancer., Stephanie N Dorman, Coby Viner, Peter K Rogan
Biochemistry Publications
Somatic mutations reported in large-scale breast cancer (BC) sequencing studies primarily consist of protein coding mutations. mRNA splicing mutation analyses have been limited in scope, despite their prevalence in Mendelian genetic disorders. We predicted splicing mutations in 442 BC tumour and matched normal exomes from The Cancer Genome Atlas Consortium (TCGA). These splicing defects were validated by abnormal expression changes in these tumours. Of the 5,206 putative mutations identified, exon skipping, leaky or cryptic splicing was confirmed for 988 variants. Pathway enrichment analysis of the mutated genes revealed mutations in 9 NCAM1-related pathways, which were significantly increased in samples with …