Abstract

BackgroundHistone post-translational modifications (PTMs) play an important role in our system by regulating the structure of chromatin and therefore contribute to the regulation of gene and protein expression. Irregularities in histone PTMs can lead to a variety of different diseases including various forms of cancer. Histone modifications are analyzed using high resolution mass spectrometry, which generate large amounts of data that requires sophisticated bioinformatics tools for analysis and visualization. PTMViz is designed for downstream differential abundance analysis and visualization of both protein and/or histone modifications.ResultsPTMViz provides users with data tables and visualization plots of significantly differentiated proteins and histone PTMs between two sample groups. All the data is packaged into interactive data tables and graphs using the Shiny platform to help the user explore the results in a fast and efficient manner to assess if changes in the system are due to protein abundance changes or epigenetic changes. In the example data provided, we identified several proteins differentially regulated in the dopaminergic pathway between mice treated with methamphetamine compared to a saline control. We also identified histone post-translational modifications including histone H3K9me, H3K27me3, H4K16ac, and that were regulated due to drug exposure.ConclusionsHistone modifications play an integral role in the regulation of gene expression. PTMViz provides an interactive platform for analyzing proteins and histone post-translational modifications from mass spectrometry data in order to quickly identify differentially expressed proteins and PTMs.

Highlights

  • Histone post-translational modifications (PTMs) play an important role in our system by regulating the structure of chromatin and contribute to the regulation of gene and protein expression

  • This generates a polypeptide of 40–50 aa residues (5–6 kDa) that contain the majority of histone PTMs and is beneficial for analyzing combinatorial histone modifications

  • To illustrate the use of PTMViz, we demonstrate the tool features on a drug abuse study in which mice were given acute injections of either a saline control or methamphetamine

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Summary

Results

To illustrate the use of PTMViz, we demonstrate the tool features on a drug abuse study in which mice were given acute injections of either a saline control or methamphetamine. The first feature of the PTM tab is an interactive data table, displaying all of the modifications included in the analysis, where the user can filter the data to observe specific samples, histone proteins, histone amino acid positions, or modification type. In the sample data provided, we identified significantly differentiating histone PTMs including histone H3K9me, H3K27me, and H4K16ac, that were regulated due to drug exposure (Fig. 3, Additional file 2: Fig. S2) and are visualized in the stacked bar chart and heatmap. Within this section the user can select the two groups of data they wish to compare and visualize as a differential analysis and in an interactive heat map (Fig. 3b) similar to the heatmap created in the protein section of the tool All these features give the user the control to view their data in many ways to achieve a maximum understanding of the results

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