title: Xilmass: A New Approach toward the Identification of Cross-Linked Peptides.
abstract: Chemical cross-linking coupled with mass spectrometry plays an important role in unravelling protein interactions, especially weak and transient ones. Moreover, cross-linking complements several structural determination approaches such as cryo-EM. Although several computational approaches are available for the annotation of spectra obtained from cross-linked peptides, there remains room for improvement. Here, we present Xilmass, a novel algorithm to identify cross-linked peptides that introduces two new concepts: (i) the cross-linked peptides are represented in the search database such that the cross-linking sites are explicitly encoded, and (ii) the scoring function derived from the Andromeda algorithm was adapted to score against a theoretical tandem mass spectrometry (MS/MS) spectrum that contains the peaks from all possible fragment ions of a cross-linked peptide pair. The performance of Xilmass was evaluated against the recently published Kojak and the popular pLink algorithms on a calmodulin-plectin complex data set, as well as three additional, published data sets. The results show that Xilmass typically had the highest number of identified distinct cross-linked sites and also the highest number of predicted cross-linked sites.
authors.affiliation: Medical Biotechnology Center, VIB , 9000 Ghent, Belgium.|Department of Biochemistry, Ghent University , 9000 Ghent, Belgium.|Bioinformatics Institute Ghent, Ghent University , 9000 Ghent, Belgium.
authors.forename: Şule
authors.initials: Ş
authors.lastname: Yılmaz
authors.affiliation: Department of Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg , 79104 Freiburg, Germany.|BIOSS Centre for Biological Signaling Studies, University of Freiburg , 79104 Freiburg, Germany.
authors.forename: Friedel
authors.initials: F
authors.lastname: Drepper
authors.affiliation: Medical Biotechnology Center, VIB , 9000 Ghent, Belgium.|Department of Biochemistry, Ghent University , 9000 Ghent, Belgium.|Bioinformatics Institute Ghent, Ghent University , 9000 Ghent, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Hulstaert
authors.affiliation: Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins , Jamova Cesta 39, 1000 Ljubljana, Slovenia.|Faculty of Medicine, University of Ljubljana , 1000 Ljubljana, Slovenia.
authors.forename: Maša
authors.initials: M
authors.lastname: Černič
authors.affiliation: Medical Biotechnology Center, VIB , 9000 Ghent, Belgium.|Department of Biochemistry, Ghent University , 9000 Ghent, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.affiliation: KU Leuven-University of Leuven , Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, 3000 Leuven, Belgium.|Institute of Molecular Biology and Biotechnology-FoRTH and Department of Biology, University of Crete , Iraklio, 71100 Crete, Greece.
authors.forename: Anastassios
authors.initials: A
authors.lastname: Economou
authors.affiliation: Department of Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg , 79104 Freiburg, Germany.|BIOSS Centre for Biological Signaling Studies, University of Freiburg , 79104 Freiburg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: Medical Biotechnology Center, VIB , 9000 Ghent, Belgium.|Department of Biochemistry, Ghent University , 9000 Ghent, Belgium.|Bioinformatics Institute Ghent, Ghent University , 9000 Ghent, Belgium.
authors.forename: Lennart
authors.initials: L
authors.lastname: Martens
authors.affiliation: Medical Biotechnology Center, VIB , 9000 Ghent, Belgium.|Department of Biochemistry, Ghent University , 9000 Ghent, Belgium.|Bioinformatics Institute Ghent, Ghent University , 9000 Ghent, Belgium.
authors.forename: Elien
authors.initials: E
authors.lastname: Vandermarliere
mesh_terms: D000465:Algorithms; D002147:Calmodulin / Q000032:analysis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D030562:Databases, Protein; D006801:Humans; D051190:Plectin / Q000032:analysis* / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D002147:Calmodulin; D003432:Cross-Linking Reagents; D051190:Plectin; D013388:Succinimides; C019358:disuccinimidyl suberate