Top-down proteomics - Archive ouverte HAL
Article Dans Une Revue Nature Reviews Methods Primers Année : 2024

Top-down proteomics

David Roberts
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Joseph Loo
Yury Tsybin
Xiaowen Liu
Si Wu
Lloyd Smith
Ying Ge
  • Fonction : Auteur correspondant

Résumé

Proteoforms, which arise from post-translational modifications, genetic polymorphisms and RNA splice variants, play a pivotal role as drivers in biology. Understanding proteoforms is essential to unravel the intricacies of biological systems and bridge the gap between genotypes and phenotypes. By analysing whole proteins without digestion, top-down proteomics (TDP) provides a holistic view of the proteome and can decipher protein function, uncover disease mechanisms and advance precision medicine. This Primer explores TDP, including the underlying principles, recent advances and an outlook on the future. The experimental section discusses instrumentation, sample preparation, intact protein separation, tandem mass spectrometry techniques and data collection. The results section looks at how to decipher raw data, visualize intact protein spectra and unravel data analysis. Additionally, proteoform identification, characterization and quantification are summarized, alongside approaches for statistical analysis. Various applications are described, including the human proteoform project and biomedical, biopharmaceutical and clinical sciences. These are complemented by discussions on measurement reproducibility, limitations and a forward-looking perspective that outlines areas where the field can advance, including potential future applications.

Dates et versions

hal-04778181 , version 1 (12-11-2024)

Identifiants

Citer

David Roberts, Joseph Loo, Yury Tsybin, Xiaowen Liu, Si Wu, et al.. Top-down proteomics. Nature Reviews Methods Primers, 2024, 4 (1), pp.38. ⟨10.1038/s43586-024-00318-2⟩. ⟨hal-04778181⟩
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