Proteome-based pathology: the next frontier in precision medicine.

Abstract

Proteins are the true machines of life. Protein enzymes carry out virtually all complex chemical transformations in living organisms, such as nucleic acid synthesis and replication, posttranslational modifications, carbohydrate and lipid metabolism, hormone biosynthesis, proteolysis, and many more. Proteins provide functional context to cells, tissues, and organisms in the form of receptors, signaling cascades, channels, and transporters. Proteins are also major structural components of the cytoskeleton and extracellular matrices. The pathobiology of virtually all diseases can be understood as the malfunctioning of any one or more of this myriad of actions that proteins perform in a spatially and temporally highly orchestrated manner. By contrast, many diseases, especially cancers, continue to be viewed in a nucleic acid-based genomic and mutation-centric manner, but is this good enough?