University of Oxford, UK
Posters & Accepted Abstracts: J Mol Genet Med
Characterizing the full repertoire of mutations in human cells is of fundamental importance to understanding their role in disease and response to treatment. Through large-scale sequencing efforts, we now have a much clearer picture of variation in human populations and in many cancer types than we did just five years ago. However, bioinformatic methods used to analyze sequencing data often regard short reads that align onto multiple regions of the genome as intractable. As a result the mutation status of hundreds of genes and regulatory elements is still unknown; our view of the mutation landscape contains many blind spots. A framework called thesaurus annotation introduces for the first time, a practical way to study variants in non-unique genomic regions. The technique links similar sites into clusters to force joint analysis of multiple genomic regions. This improves detection power and decreases the rate of false discovery by three orders of magnitude compared to previous efforts. It also generates interpretable results that can be validated through targeted re-sequencing. The thesaurus annotation software is adapted to analyze single samples, matched normal/ tumor pairs, as well as multi-sample sets (e.g., family trios). It is thus in the position to enhance our understanding of the landscape of mutations in the human genome.
Molecular and Genetic Medicine received 3571 citations as per Google Scholar report