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Published on: November 15, 2017
MSFragger: ultrafast and comprehensive peptide identification in mass spectrometry-based proteomics
Andy T Kong1,2, Felipe V Leprevost2, Dmitry M Avtonomov2
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
Nature Methods
|April 11, 2017
Summary
This study introduces MSFragger, a faster tool for identifying peptide modifications in proteomics. It significantly improves the detection of post-translational modifications, offering deeper insights into biological samples.
Area of Science:
- Proteomics
- Mass Spectrometry
- Biochemistry
Background:
- Unidentified post-translational and chemical modifications represent a significant gap in typical mass spectrometry-based proteomics.
- Existing proteome database search tools often lack the speed and comprehensiveness to identify this 'dark matter' of modifications.
Purpose of the Study:
- To develop and implement a fast fragment-ion indexing method for comprehensive peptide identification.
- To enable the open database search concept for identifying a wider range of peptide modifications.
- To improve the analysis of complex proteomic data, including post-translational modifications and cross-linked peptides.
Main Methods:
- Development of a fragment-ion indexing method.
- Implementation of the method in the MSFragger peptide identification tool.
- Application to large-scale proteomic datasets, protein-RNA cross-linked data, and affinity purification experiments.
Main Results:
- Achieved over a 100-fold improvement in speed compared to existing proteome database search tools.
- Demonstrated comprehensive identification of peptides and their modified forms using open database searching.
- Observed significant differences in modification rates across experimental conditions and a 300% increase in identified spectra for enriched proteins.
Conclusions:
- MSFragger significantly enhances the speed and scope of proteomic analysis, particularly for identifying diverse peptide modifications.
- The open database search approach empowered by MSFragger provides deeper biological insights and improves false discovery rate estimation.
- This advancement facilitates a more thorough understanding of the proteome and its dynamic modifications.
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