Clinical OMICs - Issue 5 - (Page 28)

HUMAN PROTEOME (continued from p. 6) proteins, suggesting that the human genome is more complex than previously thought. Similarly, the Munich team noted that it had discovered "hundreds of protein fragments that are encoded by DNA outside of currently known genes." These new proteins may possess novel biological properties and functions. Both teams cited the challenge of "missing proteins"-proteins that should exist, given what we know about the genome, but remain unobserved. "The depth of our analysis enabled us to identify protein products derived from two-thirds (2,555 out of 3,844) of proteins designated as missing proteins for lack of protein-based evidence," wrote the Baltimore/Bangalore researchers. "Several hypothetical proteins that we identified have a broad tissue distribution, indicating the inadequate sampling of the human proteome thus far." The Munich researchers speculated that some missing proteins may exist only during embryonic development. These scientists also suggested that many known genes have simply become nonfunctional, such as genes believed to code for olfactory receptors-an indication that modern humans no longer rely on a sophisticated sense of smell to survive. Yet another parallel finding concerned housekeeping proteins, which are highly abundant; well represented among histones, ribosomal proteins, metabolic enzymes, and cytoskeletal proteins; and constitute about 75% of total protein mass. The Munich team 28 Clinical OMICs June 12, 2014 reported finding around 10,000 such proteins "in many different places." Similarly, in their article, the Baltimore/Bangalore team noted that it "detected proteins encoded by 2,350 genes across all human cells/tissues." "One of the caveats of tissue proteomics is the contribution of vasculature, blood, and hematopoietic cells," it added. "Thus, proteins designated as housekeeping proteins based on "You can think of the human body as a huge library where each protein is a book...we now have a good first draft of that comprehensive catalog." -Akhilesh Pandey, M.D., Ph.D. analysis of tissue proteomes could be broadly grouped into two categories, those that are truly expressed in every single cell type and those that are found in every tissue (for example, endothelial cells)." Both groups highlighted the importance of their work for speeding research and translational developments. For example, the Munich team examined 24 cancer drugs whose effectiveness against 35 cancer cell lines were found to correlate strongly with their protein profiles. According to Prof. Bernhard Küster, the TUM Chair of Proteomics and Bioanalytics, "This edges us a little bit closer to the individualized treatment of patients. If we knew the protein profile of a tumor in detail, we might be able to administer drugs in a more targeted way. The new insights also allow medical researchers to investigate combinations of drugs and, thereby, tailoring treatments even more closely to a patient's individual needs." The Baltimore/Bangalore team emphasized the importance of using direct protein sequencing technologies such as mass spectrometry to complement genome annotation efforts. In addition, it outlined several proteomic research strategies that could benefit from the sampling of individual cell types of human tissues and organs and the ultimate creation of a "human cell map." "You can think of the human body as a huge library where each protein is a book," said Akhilesh Pandey, M.D., Ph.D., a professor at the McKusickNathans Institute of Genetic Medicine and of biological chemistry, pathology and oncology at the Johns Hopkins University and the founder and director of the Institute of Bioinformatics. "The difficulty is that we don't have a comprehensive catalog that gives us the titles of the available books and where to find them. We think we now have a good first draft of that comprehensive catalog." Committed to helping other researchers identify the proteins in their experiments, the Baltimore/ Bangalore team has made its human proteome catalog available as an interactive web-based resource at www.humanproteomemap.org. Similarly, the Munich team, together with software company SAP, has made its inventory freely available at www. proteomicsdb.org. www.clinicalomics.com http://www.humanproteomemap.org https://www.proteomicsdb.org https://www.proteomicsdb.org http://www.clinicalomics.com

Table of Contents for the Digital Edition of Clinical OMICs - Issue 5

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Clinical OMICs - Issue 5