Proteome, human

The human proteome is more complex than that found in invertebrates. 

The Human Proteome Is More Complex Than That of Invertebrates... 

Perhaps the biggest increase in the application and development of the MDLC technique since Cortes s book is in life sciences, which accounts for approximately half of this book. One reason for this may be due to the high level of interest in studying the human proteome (proteomics). Proteomics is such a demanding application that the separating power needed to resolve even the normal proteins in the body is so demanding that maximum separation power is needed to provide this capability. Many aspects of separations in proteomics are discussed in Chapters 9-13, 15 and 16. Chapter 14 discusses enantiomeric compound separations by MDLC. 

Qian, W.J., Liu, T., Monroe, M.E., Strittmatter, E.F., Jacobs, J.M., Kangas, L.J., Petritis, K., Camp, D.G., 2nd, Smith, R.D. (2005b). Probability-based evaluation of peptide and protein identifications from tandem mass spectrometry and SEQUEST analysis the human proteome. J. Proteome Res. 4, 53-62. 

In one study by Hood et al., 282 of 1153 identified proteins were identified by at least 2 unique tryptic peptides from FFPE prostate cancer (PCa) tissue.9 According to the gene ontology classification of the proteins identified, -65% of proteins were predicted to be intracellular proteins, while -50% of the total human proteome is predicted to be located in the intracellular compartment. Additionally, 20% of the proteins identified in the PCa tissue were classified as membrane proteins, which is significantly less than the predicted 40% for the human proteome. This relative disparity is not unexpected, considering the Liquid Tissue sample preparation kit lacks specific protocols for membrane protein extraction. The Liquid Tissue method has also been used for proteomics studies of a variety of FFPE tissue samples, including pancreatic tumors,28 squamous cell carcinoma,4 and oral human papillomavirus lesions.27... 

Abbott, A., "Workshop Prepares Ground for Human Proteome Project," Nature, 413, 763 (2001). 

Enriched subcellular compartments can be analyzed by MS/MS to determine their constituent proteins. One advantage of analysis of different cellular fractions is pre-analytical simplification that offers rewarding yields in dealing with the proteins identified in large-scale MS experiments. One of the major initiatives of the Human Proteome Organization (HUPO) is the comprehensive characterization of the complete subproteome of each cell type. 

Riding on the success of the Human Genome Project in cataloging the 30,000 to 40,000 genes of the human genome, the Human Proteome Organization (HUPO http / /www.hupo.org) has set out to determine the entire set of expressed proteins comprising the human proteome(s). As Tyers and Mann... 

Antibody coverage of the human proteome is estimated to be about 5 to 10% of all human proteins and isoforms (Valle and Jendoubi, 2003). A major bottleneck in the use of protein expression arrays is the lack of such a comprehensive set of these capture agents (Hanash, 2003). Since an equivalent of the polymerase chain reaction (PCR) process for mass amplification of low abxmdant proteins does not exist, the remaining library of proteome capture ligands will need to be generated by other means such as recombinant protein expression systems (Cahill, 2001). 

In fact, large format 2D gel electrophoresis has the ability to resolve 10,000 proteins although the process is rather tedious and suffers from low throughput (Klose and Kobalz, 1995). It is also conceivable that additional proteins may have been resolved but remain undetectable due to a lack of more sensitive protein stains. However, even with the aid of higher sensitivity staining, 2D gel electrophoresis may only be able to resolve 1 to 10% of the human proteome. 

MueUer, M., Martens, L. and Apweiler, R (2007) Annotating the Human Proteome Beyond Establishing a Parts list. Biochim Biophys Acta (BBA) -Proteins Proteomics, 1774,175. 

Gromov, P.S., Ostergaard, M., Gromova, I., Celis, J.E. (2002). Human proteomic databases, a powerful resource for functional genomics in health and disease. Prog. Biophys. Mol. Biol., 80, 3-22. 

However, it is clear that the ease of collecting proteome data currently exceeds the capacity to analyse it. Therefore, international standards are being sought for proteomic experiments, such as the proteomics standards initiative (PSI, http //psidev.source forge.net/), and the proteomics experiment data repository (PEDRo, http //pedro.man.ac.uk). The aim is to provide proteomic researchers with the opportunity to query and reproduce protocols, analyse raw or metadata from other laboratories, and to link the proteome with the respective transcriptome and the metabolome. The Human Proteome Organization (HUPO) is establishing a defined infrastructure for human data submission, and annotation for the numerous proteomic data platforms. This will also be required to effectively develop parasitic flatworm proteomics. 

Fibrous proteins represent a substantial subset of the human proteome. They include the filamentous structures found in animal hair that act as a protective and thermoregulatory outer material. They are responsible for specifying much of an animal s skeleton, and connective tissues such as tendon, skin, bone, cornea and cartilage all play an important role in this regard. Fibrous proteins are frequently crucial in locomotion and are epitomised by the muscle proteins myosin and tropomyosin and by elastic structures like titin. Yet again the fibrous proteins include filamentous assemblies, such as actin filaments and microtubules, where these provide supporting structures and tracks for the action of a variety of molecular motors. 

This daunting process should begin by establishing a comprehensive map of the healthy human proteome [68]. This formidable challenge involves organizing the data into a user-friendly format so that the information can easily be retrieved according to a variety of parameters biological system,... 

If the size of the proteome is P, there will be no more than Pn possible n- mer interactions. However, as far as drug design is concerned, the size of the interacting surfaces that could be interfered with by a small molecule is small and unlikely to include three proteins this limits the potential number of interactions to P2. If the human proteome contains 105 proteins, the number of homodimer interactions is potentially 1010. 

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