CONTEXT Protein Inference in Shotgun Proteomics—The shotgun

Discovery or shotgun proteomics has emerged as the most powerful technique to comprehensively map out a proteome. Reconstruction of protein identities from the rawmass spectrometric data constitutes a cornerstone of any shotgun proteomics workflow. The inherent uncer-tainty of mass spectrometric data and the complexity of a proteome render protein inference and the statistical val-idation of protein identifications a non-trivial task, still being a subject of ongoing research. This review aims to survey the different conceptual approaches to the differ-ent tasks of inferring and statistically validating protein identifications and to discuss their implications on the scope of proteome exploration. Molecular & Cellula