Name
Title | ||
|---|---|---|
Deuteration distribution estimation with improved sequence coverage for HX/MS experiments. |
Abstract | ||
|---|---|---|
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.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.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 data are available at Bioinformatics online. |
Year | DOI | Venue |
|---|---|---|
2010 | 10.1093/bioinformatics/btq165 | Bioinformatics |
Keywords | Field | DocType |
automatic deuteration distribution estimation,known protein sequence,deuteration distribution estimation,full deuteration distribution,entire hexicon workflow,increased sequence coverage,ms experiment,average deuteration,deuteration level,dynamic protein-level hx behavior,overall hx,improved sequence coverage,hx experiment | Data mining,Protein sequencing,Computer science,Deuterium Exchange Measurement,Feature extraction,Software,Graphical user interface,Bioinformatics,Workflow,Protein structure,Peptide sequence | Journal |
Volume | Issue | ISSN |
26 | 12 | 1367-4811 |
Citations | PageRank | References |
2 | 0.52 | 4 |
Authors | ||
11 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Xinghua Lou | 1 | 82 | 6.38 |
| Marc Kirchner | 2 | 56 | 3.89 |
| Bernhard Y. Renard | 3 | 89 | 11.65 |
| Ullrich Koethe | 4 | 249 | 22.37 |
| Sebastian Boppel | 5 | 2 | 0.52 |
| Christian Graf | 6 | 2 | 0.52 |
| Chung-Tien Lee | 7 | 2 | 0.52 |
| Judith A. J. Steen | 8 | 46 | 2.55 |
| Hanno Steen | 9 | 48 | 3.27 |
| Matthias P Mayer | 10 | 2 | 0.86 |
| Fred A. Hamprecht | 11 | 962 | 76.24 |