NPvis: An Interactive Visualizer of Peptidic Natural Product-MS/MS Matches

Abstract

Peptidic natural products (PNPs) represent a medically important class of secondary metabolites that includes antibiotics, anti-inflammatory and antitumor agents. Advances in tandem mass spectra (MS/MS) acquisition and in silico database search methods have enabled high-throughput PNP discovery. However, the resulting spectra annotations are often error-prone and their validation remains a bottleneck. Here, we present NPvis, a visualizer suitable for the evaluation of PNP-MS/MS matches. The tool interactively maps annotated spectrum peaks to the corresponding PNP fragments and allows researchers to assess the match correctness. NPvis accounts for the wide chemical diversity of PNPs that prevents the use of the existing proteomics visualizers. Moreover, NPvis works even if the exact chemical structure of the matching PNP is unknown. The tool is available online and as a standalone application. We hope that it will benefit the community by streamlining PNP data analysis and validation.

Keywords: bioinformatics; mass spectrometry; peptidic natural products; software; visualization.

Figure 1

The NPvis web server visualisation of a mass spectrum matching an (unknown) massetolide A variant. (a) The foldable control panel allows users to specify the input data and the NPvis settings. (b) The metadata panel informs about the provided spectrum and compound and the match parameters. (c) The zoomable spectrum panel highlights annotated (sky blue) and not-annotated (grey) MS/MS peaks. (d) The zoomable and rotatable compound panel presents the overall chemical structure (black) and the breakable bonds (red) of the compound. In the “PNP with modification” mode, this panel also shows the mass and proposed location of the modification (orange). In this example, the modification is +113.085 Da, which likely corresponds to an insertion of a single leucine or isoleucine residue (monoisotopic mass 113.084 Da). A user may click on an annotated peak in the spectrum panel to see the corresponding structure fragment in the compound panel (both colored blue). (e) The hideable mass error plot of absolute (Da) and relative (ppm) discrepancies between the masses of the annotated peaks and the corresponding structure fragments. (f) The scrollable list of annotated peaks highlights the selected peak (if any). The (b–f) panels are present in the downloadable interactive reports (the bottom-right button), as well as reports generated by command-line NPvis.