Library-Free Multiplexed Targeted Proteomics Enables Quantitative Protein-Level Genotyping

Existing targeted mass spectrometry methods require synthetic standard peptides, manual scan scheduling, or data libraries to quantify target proteins. Here we present GoDig-LiF, which uses spectra and retention times predicted by the Prosit-TMT model in place of data libraries, enabling targeted proteomics with only a tandem mass tag-labeled sample, target list, and mass spectrometer. We applied GoDig-LiF to the quantification of mutated proteins in cancer cell lines, including KRAS G13D.