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After 10 years of extensive proteomic research, it has become increasingly apparent that new technologies are sorely needed for detecting the low-abundance proteome-those proteins (up to 50% in any proteome) whose concentration in tissues or cells falls below the detection limits of currently available methodologies. Here we survey one such method: a combinatorial ligand library (called ProteoMiner), comprising dozens of millions of hexapeptides capable of interacting with most, if not all, proteins in any given proteome. They act by drastically reducing the signal of high-abundance species while increasing the level of the low-abundance components to bring their signal within the detection limit of present-day tools. Such a library has been tested against a number of human biological fluids, such as sera, urine, cerebrospinal fluid as well as against cell lysates (e.g., platelets, red blood cells) with interesting results.

Hexapeptide combinatorial ligand libraries: the march for the detection of the low-abundance proteome continues