title: MaRaCluster: A Fragment Rarity Metric for Clustering Fragment Spectra in Shotgun Proteomics.
abstract: Shotgun proteomics experiments generate large amounts of fragment spectra as primary data, normally with high redundancy between and within experiments. Here, we have devised a clustering technique to identify fragment spectra stemming from the same species of peptide. This is a powerful alternative method to traditional search engines for analyzing spectra, specifically useful for larger scale mass spectrometry studies. As an aid in this process, we propose a distance calculation relying on the rarity of experimental fragment peaks, following the intuition that peaks shared by only a few spectra offer more evidence than peaks shared by a large number of spectra. We used this distance calculation and a complete-linkage scheme to cluster data from a recent large-scale mass spectrometry-based study. The clusterings produced by our method have up to 40% more identified peptides for their consensus spectra compared to those produced by the previous state-of-the-art method. We see that our method would advance the construction of spectral libraries as well as serve as a tool for mining large sets of fragment spectra. The source code and Ubuntu binary packages are available at https://github.com/statisticalbiotechnology/maracluster (under an Apache 2.0 license).
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology - KTH , Box 1031, 17121 Solna, Sweden.
authors.forename: Matthew
authors.initials: M
authors.lastname: The
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology - KTH , Box 1031, 17121 Solna, Sweden.
authors.forename: Lukas
authors.initials: L
authors.lastname: Käll
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D057225:Data Mining; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010455:Peptides / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D057386:Search Engine; D012984:Software
chemical_list: D010455:Peptides
keywords: Mass spectrometry; bioinformatics; database search; hierarchical clustering; proteomics; spectral archives; spectral libraries