In the mid-1990s, as the Human Genome Project was in full swing, scientists started thinking about the protein complement of the genome, and proteomics—the identification and characterization of all of an organism’s proteins—was born. Early proteomics methods used enzymes to digest proteins into pieces that could be easily analyzed by mass spectrometry. Those methods are now mature and routinely detect peptides from thousands of proteins in a single run.
But the great strength of those methods is also their greatest weakness. What’s being analyzed is no longer the actual biological actors but the pieces left after they’ve been broken apart. Biologists and chemists are deprived of crucial information such as the masses of intact proteins and the locations of behavior-controlling modifications, such as the addition of methyl groups, sugars, or phosphate, that occur after a protein leaves the ribosome that created it.