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Deconvolution and Database Search of Complex Tandem Mass Spectra of Intact Proteins

2010; Elsevier BV; Volume: 9; Issue: 12 Linguagem: Inglês

10.1074/mcp.m110.002766

1535-9484

Xiaowen Liu, Yuval Inbar, Pieter C. Dorrestein, Colin Wynne, Nathan Edwards, Puneet Souda, Julian P. Whitelegge, Vineet Bafna, Pavel A. Pevzner,

Metabolomics and Mass Spectrometry Studies

Top-down proteomics studies intact proteins, enabling new opportunities for analyzing post-translational modifications. Because tandem mass spectra of intact proteins are very complex, spectral deconvolution (grouping peaks into isotopomer envelopes) is a key initial stage for their interpretation. In such spectra, isotopomer envelopes of different protein fragments span overlapping regions on the m/z axis and even share spectral peaks. This raises both pattern recognition and combinatorial challenges for spectral deconvolution. We present MS-Deconv, a combinatorial algorithm for spectral deconvolution. The algorithm first generates a large set of candidate isotopomer envelopes for a spectrum, then represents the spectrum as a graph, and finally selects its highest scoring subset of envelopes as a heaviest path in the graph. In contrast with other approaches, the algorithm scores sets of envelopes rather than individual envelopes. We demonstrate that MS-Deconv improves on Thrash and Xtract in the number of correctly recovered monoisotopic masses and speed. We applied MS-Deconv to a large set of top-down spectra from Yersinia rohdei (with a still unsequenced genome) and further matched them against the protein database of related and sequenced bacterium Yersinia enterocolitica . MS-Deconv is available at http://proteomics.ucsd.edu/Software.html.