Deuteration distribution estimation with improved sequence coverage for HX/MS experiments

MOTIVATION Time-resolved hydrogen exchange (HX) followed by mass spectrometry (MS) is a key technology for studying protein structure, dynamics and interactions. HX experiments deliver a time-dependent distribution of deuteration levels of peptide sequences of the protein of interest. The robust and complete estimation of this distribution for as many peptide fragments as possible is instrumental to understanding dynamic protein-level HX behavior. Currently, this data interpretation step still is a bottleneck in the overall HX/MS workflow. RESULTS We propose HeXicon, a novel algorithmic workflow for automatic deuteration distribution estimation at increased sequence coverage. Based on an L(1)-regularized feature extraction routine, HeXicon extracts the full deuteration distribution, which allows insight into possible bimodal exchange behavior of proteins, rather than just an average deuteration for each time point. Further, it is capable of addressing ill-posed estimation problems, yielding sparse and physically reasonable results. HeXicon makes use of existing peptide sequence information, which is augmented by an inferred list of peptide candidates derived from a known protein sequence. In conjunction with a supervised classification procedure that balances sensitivity and specificity, HeXicon can deliver results with increased sequence coverage. AVAILABILITY The entire HeXicon workflow has been implemented in C++ and includes a graphical user interface. It is available at http://hci.iwr.uni-heidelberg.de/software.php. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.