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The Monkey King and Pigsy Ferrying the Proteomic Sutras in the 3rd Millenium: a Chronicle S-08.01.4-001 P.G. RighettiI IPolitecnico di Milano, Milano, Italy In the saga Journey to the West (16 th century, Ming Dynasty) the Monkey King (a divinity in the Chinese Olympus) helps the Buddhist monk Xuanzang (Tripitaka) to retrieve and bring back to China the sacred Buddhist texts (the sutras), against evil forces contrasting his mission. Out of metaphor, the superpower that ferried the proteomics sutras in the third millennium is definitely mass spectrometry (MS), especially the family of Orbitrap machines. Yet, notwithstanding the extraordinary power of modern MS, plenty of low-abundance proteins (LAP) escape detection and identification as they are buried underneath the high abundance species (HAP), which swamp their weak signals. Going back to the saga, another divinity helped Tripitaka to escape evil forces on his way back to China: Pigsy, half a man, half a pig, whose main connotation was tremendous avidity for food. So, in the proteomics filed, the second divinity helping detection of LAPs is certainly the combinatorial peptide ligand library (CPLL) methodology, which is here presented. CPLLs, like Pigsy, have a tremendous avidity for LAPs and enhance their signal up to four orders of magnitude. I will present here some outstanding results obtained when analysing a few biological fluids such as the cytoplasm of the red blood cells, where as many as 1578 species have been identified, as well as of the human cerebrospinal fluid and sera. In other mammalian fluids the harvest has also been bountiful: in goat’s milk, 452 unique proteins have just been identified, vs. a handful only a while ago. In bovine colostrum, in which 85% of the species are immunoglobulins,1786 proteins have now been catalogued, an exorbitant number, indeed. Among them a set of 93 proteins involved in wound healing process was identified and clustered on the basis of different biological functions. Boschetti, P.G. Righetti, Low-Abundance Proteome Discovery. State of the Art and Protocols, Elsevier, Amsterdam, 2013, 341 pp.