Overview of bottom-up proteomics and proteogenomic mapping. After cell lysis, proteins are extracted from a biological sample and are proteolytically digested into peptides. The peptide mixture is commonly separated by liquid chromatography and introduced into a tandem mass spectrometer, which produces MS/MS spectra. The resulting spectra are matched against an in silico translation and proteolytic digestion of genomic DNA sequences in all six reading frames to identify peptides. The matched peptides are then mapped back to the DNA sequences to identify the genomic loci for the analyzed proteins.