Abstract:
\"Making the Case for Functional Proteomics\" first differentiates the Functional Proteome from the products of genetic protein expression. Qualitatively, the prevalence of posttranslational modifications (PTMs) virtually insures that individual, functional proteins do not equate to their genetic expression counterparts. Quantitatively, considering the frequency of PTMs and a conservative estimate of the number of functional entities arising from protein interactions, the size of the Functional Proteome exceeds that of the human genome by at least two orders of magnitude. The human genome does not, cannot, map the Functional Proteome. Further, the collective genome of the human microbiome dwarfs the human genome. With these facts established, \"Making the Case…\" proceeds to examine Functional Proteomics (of which both \"gene expression\" and \"epigenetics\" are but parts of a larger whole) within the context of Systems Biology, concluding that functionally related networks comprise the dominant motif for biological activity. Creating just such a network focus is essential in not only expanding basic knowledge but also in applying that knowledge in the pragmatic efforts of drug and biomarker development. Outlines for development of drugs and biomarkers, as well as the realization of precision medicine, within a functional proteomics-based, network motif are provided. The chapter proceeds to asses both the knowledge base and the tools to fully embrace Functional Proteomics. Given the decades-long infatuation with the reductionism of genomics, it is not surprising that both the proteomics knowledge base and tools are assessed as poor to fair. However, even a minor shift in research funding and a renewed challenge to methods developers will rapidly improve the current situation. Adoption of the included \"Roadmap\" will realistically make the twenty-first century the century of a long-awaited revolution in biology.