Mass Spectrometry Driven Biological Discovery

Proteomics emerged from the convergence of large‐scale sequencing of genomes and high sensitivity mass spectrometry. A key element has been the use of computational algorithms to compare mass spectrometry data of peptides and proteins, in particular tandem mass spectrometry data, to the sequences of an organism to identify amino acid sequences. Algorithms to compare sequences to spectra and determine closeness of fit have enabled large‐scale experiments by simplifying and automating data analysis. Simplification of data analysis unleashed the power for tandem mass spectrometers for mixture analysis. By combining high resolution separation techniques such as 1 or 2‐dimensional HPLC with tandem mass spectrometry complex proteolytically digested protein mixtures can be analyzed. This approach to protein biochemistry has been termed “shotgun proteomics” when applied to mixtures of proteins. By using these techniques protein complexes, organelles, cells and tissues have been analyzed providing a new analytical paradigm to study biological systems.