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Bottom-up proteomics (mass spectrometry analysis of peptides obtained by proteolysis and separated by liquid chromatography, (LC-MS/MS)) is one of the most frequently used techniques for identifying and characterizing proteins in biological samples. A key element of the analysis is database searching when the mass spectra of the peptides are compared with a database of theoretically computed (or experimental) peptide spectra. Here we discuss the main computational approaches to spectrum database searching and the statistical analysis of the results.