Cytognomix’s Shannon pipeline has been highlighted in a report published describing the 2013 annual scientiﬁc meeting of the Human Genome Variation Society (HGVS) in Paris, France. The paper’s authors, Sian Ellard,George P. Patrinos, and William S. Oetting, write:
“Although NGS can identify numerous sequence variants, a major problem is predicting the functional consequence of mutations identiﬁed after sequencing. Much work has been done on determining the functionality of protein coding mutations within exon sequences, but signiﬁcant mutations that affect splicing or gene expression have not been comprehensively assessed. Peter Rogan, of the Schulich School of Medicine, Western University, London,Canada, has taken on this task and presented some of his results in his talk “Genome-wide prediction and validation of mRNA splicing mutations in cancer.” Using Shannon information theory, software packages were created for genome-scale analysis of variants within splice sites that alter binding site strength [Shirley et al., 2013] and to predict the transcript isoforms generated by splicing mutations [Mucaki et al., 2013]. Variants within the BRCA1 and BRCA2 genes were used to test their model and were grouped into four functional states: wild type, leaky mutations with residual activity, inactivating mutations, and cryptic splicing. Predicted effects of 50% of these calls were conﬁrmed using RNAseq analysis. Additional efforts underway include predicting functional mutations in promoter and intronic regions and the potential effects of mutations in regulatory splicing elements with information theory-based models. The goal is to use these software tools to perform a genome-scale mutation analysis to identify functional variants outside the coding regions affecting either splicing or expression levels.”
Citation: Ellard S, Patrinos GP, and Oetting WS, Clinical Applications of Next-Generation Sequencing: The 2013 Human Genome Variation Society Scientiﬁc Meeting, Human Mutation, DOI: 10.1002/humu.22400, 2013.