The Size of the Human Proteome: The Width and Depth

Area of Science:

• Proteomics and Bioinformatics
• Molecular Biology
• Genomics

Background:

• The human proteome is dynamic, with proteins varying in form (proteoforms) and quantity.
• Understanding proteoform diversity is crucial for comprehending biological function in different tissues.

Purpose of the Study:

• To theoretically predict the number of human proteoforms using meta-analysis of the neXtProt knowledge base.
• To explore the impact of alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs) on proteoform diversity.

Main Methods:

• Meta-analysis of the neXtProt knowledge base.
• Theoretical prediction of proteoform numbers considering different modification scenarios.
• Generation of distribution histograms for protein copy numbers in plasma, liver, and HepG2 cells.

Main Results:

• A bell-shaped distribution histogram was generated for protein copy numbers.
• The study considered three distinct models for the occurrence of AS, SAPs, and PTMs.
• Experimental validation of proteoforms is currently limited by technological sensitivity.

Conclusions:

• Metabioinformatics approaches can estimate the number of proteoforms for gene groups.
• The study provides a framework for predicting proteoform diversity based on genetic and posttranslational events.