RegulationSpotter: annotation and interpretation of extratranscriptic DNA variants

Abstract

RegulationSpotter is a web-based tool for the user-friendly annotation and interpretation of DNA variants located outside of protein-coding transcripts (extratranscriptic variants). It is designed for clinicians and researchers who wish to assess the potential impact of the considerable number of non-coding variants found in Whole Genome Sequencing runs. It annotates individual variants with underlying regulatory features in an intuitive way by assessing over 100 genome-wide annotations. Additionally, it calculates a score, which reflects the regulatory potential of the variant region. Its dichotomous classifications, 'functional' or 'non-functional', and a human-readable presentation of the underlying evidence allow a biologically meaningful interpretation of the score. The output shows key aspects of every variant and allows rapid access to more detailed information about its possible role in gene regulation. RegulationSpotter can either analyse single variants or complete VCF files. Variants located within protein-coding transcripts are automatically assessed by MutationTaster as well as by RegulationSpotter to account for possible intragenic regulatory effects. RegulationSpotter offers the possibility of using phenotypic data to focus on known disease genes or genomic elements interacting with them. RegulationSpotter is freely available at https://www.regulationspotter.org.

Figure 1.

Overview of features that can be assessed in a single RegulationSpotter VCF analysis run. Depending upon a variant's localisation, different aspects are analysed either by RegulationSpotter or MutationTaster. ^(*) It should be noted that intragenic variants are always additionally analysed by RegulationSpotter to account for the possible regulatory effects of e.g. non-coding variants. UTR: untranslated region; CDS: coding sequence; TSS: transcription start site; NMD: nonsense-mediated mRNA decay.

Figure 2.

Screenshot of the colour-coded results matrix. Variants chosen to be displayed are organised in a summary table (left part) and in a colour-coded matrix (right part) in order to allow the rapid overview of every variant. Users can follow hyperlinks to study every variant in further detail.