Deuteros 2.0: peptide-level significance testing of data from hydrogen deuterium exchange mass spectrometry

Abstract

Summary: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire conformational networks. As such, the number of necessary cross-state comparisons quickly increases as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even fewer which offer statistical analysis and advanced visualization. Following the feedback from our original software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfill a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features.

Availability and implementation: Deuteros 2.0 can be downloaded for both Windows and MacOS from https://github.com/andymlau/Deuteros_2.0 under the Apache 2.0 license.

Fig. 1.

Statistical testing in Deuteros 2.0. Two statistical tests are offered in Deuteros 2.0: (a) peptide and (b) hybrid significance tests. Statistical models are applied to differential HDX-MS data to identify peptides which show statistically significant changes in deuteration between experimental states. Significant peptides are described as regions exhibiting deprotection or protection according to the direction of the deuteration difference. Data shown represent the XylE Δ(E397Q-WT) dataset from Martens et al. (2018)