Protein identification by spectral networks analysis

@article{citeulike:1526846, abstract = {Advances in tandem mass spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra. As a result, the existing approaches that compare spectra against databases are already facing a bottleneck, particularly when interpreting spectra of modified peptides. Here we explore a concept that allows one to perform an MS/MS database search without ever comparing a spectrum against a database. We propose to take advantage of spectral pairs, which are pairs of spectra obtained from overlapping (often nontryptic) peptides or from unmodified and modified versions of the same peptide. Having a spectrum of a modified peptide paired with a spectrum of an unmodified peptide allows one to separate the prefix and suffix ladders, to greatly reduce the number of noise peaks, and to generate a small number of peptide reconstructions that are likely to contain the correct one. The MS/MS database search is thus reduced to extremely fast pattern-matching (rather than time-consuming matching of spectra against databases). In addition to speed, our approach provides a unique paradigm for identifying posttranslational modifications by means of spectral networks analysis. 10.1073/pnas.0701130104}, author = {Bandeira, Nuno and Tsur, Dekel and Frank, Ari and Pevzner, Pavel A. }, citeulike-article-id = {1526846}, doi = {10.1073/pnas.0701130104}, journal = {PNAS}, keywords = {peptide-identification, proteomics, tandem-mass-spectrometry}, month = {April}, number = {15}, pages = {6140--6145}, posted-at = {2007-08-07 15:18:21}, priority = {4}, title = {Protein identification by spectral networks analysis}, url = {http://dx.doi.org/10.1073/pnas.0701130104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1526846 L3 - citeulike-article-id:1526846 TI - Protein identification by spectral networks analysis JF - PNAS VL - 104 IS - 15 SP - 6140 EP - 6145 N2 - Advances in tandem mass spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra. As a result, the existing approaches that compare spectra against databases are already facing a bottleneck, particularly when interpreting spectra of modified peptides. Here we explore a concept that allows one to perform an MS/MS database search without ever comparing a spectrum against a database. We propose to take advantage of spectral pairs, which are pairs of spectra obtained from overlapping (often nontryptic) peptides or from unmodified and modified versions of the same peptide. Having a spectrum of a modified peptide paired with a spectrum of an unmodified peptide allows one to separate the prefix and suffix ladders, to greatly reduce the number of noise peaks, and to generate a small number of peptide reconstructions that are likely to contain the correct one. The MS/MS database search is thus reduced to extremely fast pattern-matching (rather than time-consuming matching of spectra against databases). In addition to speed, our approach provides a unique paradigm for identifying posttranslational modifications by means of spectral networks analysis. 10.1073/pnas.0701130104 KW - peptide-identification KW - proteomics KW - tandem-mass-spectrometry AU - Bandeira, Nuno AU - Tsur, Dekel AU - Frank, Ari AU - Pevzner, Pavel PY - 2007/04/10/ UR - http://dx.doi.org/10.1073/pnas.0701130104 ER -