Improved de novo peptide sequencing using LC retention time information
peer-reviewed · Algorithms for Molecular Biology · 2018
| Date | 2018-08-29 |
| Type | peer-reviewed |
| Venue | Algorithms for Molecular Biology |
| Publisher | Springer Science and Business Media LLC |
| Contribution | algorithm |
| DOI | 10.1186/s13015-018-0132-5 |
Abstract
Background Liquid chromatography combined with tandem mass spectrometry is an important tool in proteomics for peptide identification. Liquid chromatography temporally separates the peptides in a sample. The peptides that elute one after another are analyzed via tandem mass spectrometry by measuring the mass-to-charge ratio of a peptide and its fragments. De novo peptide sequencing is the problem of reconstructing the amino acid sequences of a peptide from this measurement data. Past de novo sequencing algorithms solely consider the mass spectrum of the fragments for reconstructing a sequence. Results We propose to additionally exploit the information obtained from liquid chromatography. We study the problem of computing a sequence that is not only in accordance with the experimental mass spectrum, but also with the chromatographic retention time. We consider three models for predicting the retention time and develop algorithms for de novo sequencing for each model. Conclusions Based on an evaluation for two prediction models on experimental data from synthesized peptides we conclude that the identification rates are improved by exploiting the chromatographic information. In our evaluation, we compare our algorithms using the retention time information with algorithms using the same scoring model, but not the retention time.
Methods and tools
- Retention-time-aware de novo sequencing: Extends the symmetric difference scoring model with the chromatographic retention time, asking for a sequence consistent with both the fragment spectrum and the observed elution time. Develops an algorithm for each of three retention-time prediction models.