How low can you go? A current perspective on low-abundance proteomics

The advent of proteomics brought with it the promise of protein-based diagnostics, bound to be more efficient and informative due to the intrinsic role of proteins in the molecular and cellular processes that are at the basis of both health and disease. Alas, the vast dynamic range of the proteome in biological fluids has greatly hampered the expected advances in medicine. Low-abundance proteins, which carry great diagnostic potential, are often obscured by the presence of high-abundance proteins and their identification remains technically challenging, despite the numerous developed strategies. Herein, we not only discuss the complexity of the human proteome, but also cover the most commonly used approaches for enhancing the visibility of these highly sought-after biological entities, aimed at the perhaps larger goal of this research: the discovery of biomarkers, which may lead to the long-expected personalized medicine.