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How many human proteoforms are there?

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The human proteome

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Area of Science:

  • Proteomics and Molecular Biology
  • Genomics and Post-Translational Modifications

Background:

  • Decades of research on proteins and post-translational modifications (PTMs) still leave fundamental questions about their composition and function.
  • The complexity of the human proteome arises from combinations of DNA, RNA, and PTM variations, but the full extent is unknown.

Purpose of the Study:

  • To assess current knowledge on protein diversity and PTMs using existing databases and measurement strategies.
  • To determine the number of distinct protein forms (proteoforms) generated from human genes.
  • To explore methods for improving PTM measurements and linking them to biological function.

Main Methods:

  • Review of current databases and PTM knowledge.
  • Analysis of mass spectrometry-based proteomics data.
  • Framework development for assessing protein-level variation.

Main Results:

  • The study examines prevailing notions about protein modification numbers and their combinatorial impact on proteome diversity.
  • It frames key issues and paradoxes in determining protein variation and PTMs.
  • Existing data is assessed to address the question of proteoform count.

Conclusions:

  • Significant gaps remain in understanding the full complexity of the human proteome.
  • Improved measurement strategies are needed to regularize protein biology and associate PTMs with function.
  • Accurate determination of proteoform numbers is crucial for advancing health and disease research.