Proteomes Are of Proteoforms: Embracing the Complexity.

Area of Science:

• Biochemistry
• Proteomics
• Molecular Biology

Background:

• Proteomes are significantly more complex than genomes or transcriptomes.
• Analysis of canonical proteins (Proteome-lite) is insufficient for understanding biological mechanisms.
• Proteoforms, including isoforms, splice variants, and post-translational modifications (PTMs), represent the true complexity of the proteome.

Purpose of the Study:

• To critically evaluate current analytical methods for proteome depth.
• To identify limitations and areas for improvement in quantitative proteome characterization.
• To propose a next-generation approach for comprehensive proteomic analysis.

Main Methods:

• Critical evaluation of existing proteomic analytical techniques.
• Assessment of pros and cons of various approaches for proteome depth.
• Discussion of necessary refinements for quantitative proteome characterization.

Main Results:

• Current methods for analyzing proteome depth have limitations.
• A significant gap exists between analyzing canonical proteins and the actual proteome complexity.
• Improvements are needed in quantitative characterization of proteoforms.

Conclusions:

• A transdisciplinary, integrated approach combining current proteomic methods is essential.
• Future advances require moving beyond a primary focus on proteo-genomics and proteo-transcriptomics.
• Embracing proteome complexity is crucial for dissecting biological mechanisms and identifying biomarkers/drug targets.