4.8 Review

The Human Proteoform Project: Defining the human proteome

Journal

SCIENCE ADVANCES
Volume 7, Issue 46, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abk0734

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Funding

  1. NCATS NIH HHS [UL1 TR001422] Funding Source: Medline
  2. NHLBI NIH HHS [R01 HL096971] Funding Source: Medline
  3. NIGMS NIH HHS [P41 GM108569, R01 GM103479, R01 GM117058, R35 GM126914, R01 GM125085] Funding Source: Medline

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Understanding the structure and properties of proteins is crucial in deciphering biological functions. The concept of defining the human proteome as a reference set of proteoforms is proposed, with a call for improved technologies in a two-pronged strategy.
Proteins are the primary effectors of function in biology, and thus, complete knowledge of their structure and properties is fundamental to deciphering function in basic and translational research. The chemical diversity of proteins is expressed in their many proteoforms, which result from combinations of genetic polymorphisms, RNA splice variants, and posttranslational modifications. This knowledge is foundational for the biological complexes and networks that control biology yet remains largely unknown. We propose here an ambitious initiative to define the human proteome, that is, to generate a definitive reference set of the proteoforms produced from the genome. Several examples of the power and importance of proteoform-level knowledge in disease-based research are presented along with a call for improved technologies in a two-pronged strategy to the Human Proteoform Project.

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