Human proteome size as a function of development of experimental technologies and bioinformatics methods

Our research presents a retrospective analysis of changes in information on the number of human proteoforms, post-translational modification (PTM) events, alternative splicing (AS), single-amino acid polymorphisms (SAP) associated with protein-coding genes in the NextProt database. In 2016, our group proposed three mathematical models for predicting the number of different proteins (proteoforms) in the human proteome. Eight years later, we compared the original data of information resources and their contribution to the prediction results, comparing the differences with new approaches to experimental and bioinformatics analysis of protein modifications.
This work is designed to update information on the status of records in databases on identified proteoforms since 2016, as well as to identify trends in changes in the numbers of these records. It was found that, according to various information models, modern experimental methods allow us to identify from 5 to 125 million different proteoforms – proteins formed as a result of alternative splicing, implementation of single-nucleotide polymorphisms and post-translational modifications in various combinations at the proteomic level. This result reflects an increase in the size of the human proteome by 20 or more times over the past 8 years.
The work was carried out within the framework of the Fundamental Research Program in the Russian Federation for the long-term period 2021-2030 (No122030100168-2).