Challenges of the Human Proteome Project: 10-Year Experience of the Russian Consortium

被引：7

作者：

Archakov, Alexander I. ^{[1
]}

Aseev, Alexander L. ^{[2
]}

Bykov, Victor A. ^{[3
]}

Grigoriev, Anatoly I. ^{[4
]}

Govorun, Vadim M. ^{[5
]}

Ilgisonis, Ekaterina V. ^{[1
]}

Ivanov, Yuri D. ^{[1
]}

Ivanov, Vadim T. ^{[6
]}

Kiseleva, Olga I. ^{[1
]}

Kopylov, Arthur T. ^{[1
]}

Lisitsa, Andrey V. ^{[1
]}

Mazurenko, Sergey N. ^{[7
]}

Makarov, Alexander A. ^{[8
]}

Naryzhny, Stanislav N. ^{[1
]}

Pleshakova, Tatiana O. ^{[1
]}

Ponomarenko, Elena A. ^{[1
]}

Poverennaya, Ekaterina V. ^{[1
]}

Pyatnitskii, Mikhail A. ^{[1
]}

Sagdeev, Renad Z. ^{[9
]}

Skryabin, Konstantin G. ^{[10
]}

Zgoda, Victor G. ^{[1
]}

机构：

[1] Inst Biomed Chem, Moscow 119435, Russia

[2] Inst Semicond Phys, Novosibirsk 630090, Russia

[3] NT MDT, Moscow 124460, Russia

[4] Inst Med & Biol Problems, Moscow 123007, Russia

[5] Fed Res & Clin Ctr Phys Chem Med, Moscow 119435, Russia

[6] Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia

[7] Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia

[8] Engelhardt Inst Mol Biol, Moscow 119991, Russia

[9] Int Tomog Ctr, Novosibirsk 630090, Russia

[10] Fed Res Ctr Fundamentals Biotechnol, Moscow 119071, Russia

来源：

JOURNAL OF PROTEOME RESEARCH | 2019年 / 18卷 / 12期

关键词：

human proteome; mass-spectrometry; Chromosome-Centric Human Proteome Project (C-HPP); sensitivity; fractionation; missing proteins; atomic force microscopy; proteoforms; low-abundant proteins; ATOMIC-FORCE MICROSCOPY; MASS-SPECTROMETRY; MESSENGER-RNA; LIVER-TISSUE; DEPLETED PLASMA; TRANSCRIPTOME; SPECIFICITY; GENERATION; NANOWIRE; NUMBER;

D O I：

10.1021/acs.jproteome.9b00358

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

This manuscript collects all the efforts of the Russian Consortium, bottlenecks revealed in the course of the C-HPP realization, and ways of their overcoming. One of the main bottlenecks in the C-HPP is the insufficient sensitivity of proteomic technologies, hampering the detection of low- and ultralow-copy number proteins forming the "dark part" of the human proteome. In the frame of MP-Challenge, to increase proteome coverage we suggest an experimental workflow based on a combination of shotgun technology and selected reaction monitoring with two-dimensional alkaline fractionation. Further, to detect proteins that cannot be identified by such technologies, nanotechnologies such as combined atomic force microscopy with molecular fishing and/or nanowire detection may be useful. These technologies provide a powerful tool for single molecule analysis, by analogy with nanopore sequencing during genome analysis. To systematically analyze the functional features of some proteins (CP50 Challenge), we created a mathematical model that predicts the number of proteins differing in amino acid sequence: proteoforms. According to our data, we should expect about 100 000 different proteoforms in the liver tissue and a little more in the HepG2 cell line. The variety of proteins forming the whole human proteome significantly exceeds these results due to post-translational modifications (PTMs). As PTMs determine the functional specificity of the protein, we propose using a combination of gene-centric transcriptome-proteomic analysis with preliminary fractionation by two-dimensional electrophoresis to identify chemically modified proteoforms. Despite the complexity of the proposed solutions, such integrative approaches could be fruitful for MP50 and CP50 Challenges in the framework of the C-HPP.

引用

页码：4206 / 4214

页数：9

共 60 条

[1] Global signatures of protein and mRNA expression levels [J].