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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\u20138, 2008; Walzthoeni et al., Nat Methods 9(9):901\u20133, 2012), pLink (Yang et al., Nat Methods 9(9):904\u20136, 2012), ProteinProspector (Chu et al., Mol Cell Proteomics 9:25\u201331, 2010; Trnka et al., 13(2):420\u201334, 2014) and Kojak (Hoopmann et al., J Proteome Res 14(5):2190\u2013198, 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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.<\/jats:p>\n                <jats:p>ECL identified more non-redundant cross-linked peptides than xQuest, pLink, and ProteinProspector. Experiments showed that about 30 <jats:italic>%<\/jats:italic> 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 \u00c5.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-016-1073-y","type":"journal-article","created":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T10:11:30Z","timestamp":1463825490000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["ECL: an exhaustive search tool for the identification of cross-linked peptides using whole database"],"prefix":"10.1186","volume":"17","author":[{"given":"Fengchao","family":"Yu","sequence":"first","affiliation":[]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[]},{"given":"Weichuan","family":"Yu","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,5,20]]},"reference":[{"key":"1073_CR1","doi-asserted-by":"publisher","first-page":"5802","DOI":"10.1073\/pnas.090099097","volume":"97","author":"MM Young","year":"2000","unstructured":"Young MM, Tang N, Hempel JC, Oshiro CM, Taylor EW, Kuntz ID, Gibson BW, Dollinger G. 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