The Size of the Human Proteome: The Width and Depth
By E. Ponomarenko, E. Poverennaya, E. Ilgisonis, M. Pyatnitskiy, A. Kopylov, V. Zgoda, A. Lisitsa, A. Archakov. 2016
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This work discusses bioinformatics and experimental approaches to explore the human proteome, a constellation of proteins expressed in different tissues and organs. As the human proteome is not a static entity, it seems necessary to estimate the number of different protein species (proteoforms) and measure the number of copies of the same protein in a specific tissue. Here, meta-analysis of neXtProt knowledge base is proposed for theoretical prediction of the number of different proteoforms that arise from alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs). Three possible cases are considered: (1) PTMs and SAPs appear exclusively in the canonical sequences of proteins, but not in splice variants; (2) PTMs and SAPs can occur in both proteins encoded by canonical sequences and in splice variants; (3) all modification types (AS, SAP, and PTM) occur as independent events. Experimental validation of proteoforms is limited by the analytical sensitivity of proteomic technology. A bell-shaped distribution histogram was generated for proteins encoded by a single chromosome, with the estimation of copy numbers in plasma, liver, and HepG2 cell line. The proposed metabioinformatics approaches can be used for estimation of the number of different proteoforms for any group of protein-coding genes.
Subfields: Molecular Biology, Spectroscopy
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Citations in the corpus
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- Yuel: Compound-Protein Interaction Prediction with High Generalizability (2021, background): “…that the chemical space of potential drugs may be as large as 10 60 small molecules 14 and the human proteome consist of millions of protein species 15,16 , a natural question that arises is whether current neural network models are reliable for drug virtual screening when training on a tiny…”