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ECL: An Exhaustive Search Tool for the Identification of Cross-linked Peptides Using Whole Database

Authors Yu, Fengchao HKUST affiliated (currently or previously)
Li, Ning View this author's profile
Yu, Weichuan View this author's profile
Issue Date 2016
Source BMC Bioinformatics , v. 17, (1), 2016, article number 217
Summary Background: Chemical cross-linking combined with mass spectrometry (CX-MS) is a high-throughput approach to studying protein-protein interactions. The number of peptide-peptide combinations grows quadratically with respect to the number of proteins, resulting in a high computational complexity. Widely used methods including xQuest (Rinner et al., Nat Methods 5(4): 315-8, 2008; Walzthoeni et al., Nat Methods 9(9): 901-3, 2012), pLink (Yang et al., Nat Methods 9(9): 904-6, 2012), ProteinProspector (Chu et al., Mol Cell Proteomics 9: 25-31, 2010; Trnka et al., 13(2): 420-34, 2014) and Kojak (Hoopmann et al., J Proteome Res 14(5): 2190-198, 2015) avoid searching all peptide-peptide combinations by pre-selecting peptides with heuristic approaches. However, pre-selection procedures may cause missing findings. The most intuitive approach is searching all possible candidates. A tool that can exhaustively search a whole database without any heuristic pre-selection procedure is therefore desirable. Results: We have developed a cross-linked peptides identification tool named ECL. It can exhaustively search a whole database in a reasonable period of time without any heuristic pre-selection procedure. Tests showed that searching a database containing 5200 proteins took 7 h. ECL identified more non-redundant cross-linked peptides than xQuest, pLink, and ProteinProspector. Experiments showed that about 30 % of these additional identified peptides were not pre-selected by Kojak. We used protein crystal structures from the protein data bank to check the intra-protein cross-linked peptides. Most of the distances between cross-linking sites were smaller than 30 angstrom. Conclusions: To the best of our knowledge, ECL is the first tool that can exhaustively search all candidates in cross-linked peptides identification. The experiments showed that ECL could identify more peptides than xQuest, pLink, and ProteinProspector. A further analysis indicated that some of the additional identified results were thanks to the exhaustive search.
ISSN 1471-2105
Language English
Format Article
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