Large‐scale development and implementation of highly sensitive, multiplex MRM‐based assays for quantification of proteins in biological settings (475.2)

Abstract

Proteins carry out the biological functions of our cells and form the basis of diagnostic tests and treatments, yet over 95% of human proteins can’t be studied because we lack reliable laboratory methods (assays) for quantifying their abundances. This lack of standardized assays for quantifying the vast majority of human proteins has left the proteome clinically inaccessible, contributed to poor inter‐laboratory reproducibility of preclinical research, and indeed is the biggest impediment to translating novel protein diagnostics into clinical use, as well as a major impediment to systems biology studies needing to interrogate biologically relevant numbers of samples. Selected/multiple reaction monitoring mass spectrometry (S/MRM), especially coupled to the enrichment of target analytes, promises to relieve this limitation by offering a robust platform that enables efficient generation of highly sensitive, multiplex‐able assays that are standardized to support high reproducibility across laboratories and platforms. This seminar will review current data on the large‐scale generation, implementation, and performance of highly multiplex MRM‐based assays in biological settings relevant to cancer. En masse, these studies establish the feasibility and utility of scaling to develop analytically validated, MRM‐based assays to quantify all human proteins.