Almost all large-scale projects in mass spectrometry-based proteomics use trypsin to convert
protein mixtures into more readily analyzable peptide populations. When searching peptide
fragmentation spectra against sequence databases, potentially matching peptide sequences
can be required to conform to tryptic specificity, namely, cleavage exclusively C-terminal to
arginine or lysine. In many published reports, however, significant numbers of proteins are
identified by non-tryptic peptides. Here we use the sub-parts per million mass accuracy of a …