[PCR analysis of the expression of chromosome 18 genes in human liver tissue: interindividual variability]. / PTsR-analiz ékspressii genov khromosomy 18 v tkani pecheni cheloveka: mezhindividual'naia variabel'nost'.

Using human chromosome 18 (Ch18) genes as an example, a PCR analysis of the interindividual variability of gene expression in liver tissue was performed. Although the quantitative profiles of the Ch18 transcriptome, expressed in the number of cDNA copies per single cell, showed a high degree of correlation between donors (Pearson correlation coefficients ranged from 0.963 to 0.966), the expression of the significant number of genes (from 13% to 19%, depending on the method of experimental data normalization) varied by more than 4-fold when comparing donors pairwise. At the same time, the proportion of differentially expressed genes increased with a decrease in the level of their expression. It is shown that the higher quantitative variability of low-abundance transcripts is mainly not technical, but biological. Bioinformatic analysis of the interindividual variability of the differential expression of chromosome 18 genes in human liver tissue did not reveal any statistically significant groups of genes related to certain biological processes that indicated a rather transient nature of the interindividual variability of their expression, probably reflecting the response of cells of an individual to specific external stimuli.

[Medical subject headings for the scientific groups evolution analysis on the example of academician A.I. Archakov's scientific school]. / Meditsinskie predmetnye rubriki dlia analiza évoliutsii nauchnykh grupp na primere nauchnoi shkoly akademika A.I. Archakova.

This paper proposes a method of comparative analysis of scientific trajectories based on bibliographic profiles. The bibliographic profile ("meshprint") is a list of MeSH terms (key terms used to index articles in the PubMed), indicating the relative frequency of occurrence of each term in the scientist's articles. Comparison of personalized bibliographic profiles can be represented in the form of a semantic network, where the nodes are the names of scientists, and the relationships are proportional to the calculated measures of similarity of bibliographic profiles. The proposed method was used to analyze the semantic network of scientists united by the academic school of the academician A.I. Archakov. The results of the work allowed us to show the relationship between the scientific trajectories of one scientific school and to correlate the results with world trends.

Methods of Computational Interactomics for Investigating Interactions of Human Proteoforms.

Human genome contains ca. 20,000 protein-coding genes that could be translated into millions of unique protein species (proteoforms). Proteoforms coded by a single gene often have different functions, which implies different protein partners. By interacting with each other, proteoforms create a network reflecting the dynamics of cellular processes in an organism. Perturbations of protein-protein interactions change the network topology, which often triggers pathological processes. Studying proteoforms is a relatively new research area in proteomics, and this is why there are comparatively few experimental studies on the interaction of proteoforms. Bioinformatics tools can facilitate such studies by providing valuable complementary information to the experimental data and, in particular, expanding the possibilities of the studies of proteoform interactions.

[Proteoforms: Methods of Analysis and Clinical Prospects].

A critical analysis of proteomes provides a basis for understanding the operation of complex biochemical systems. A personalized approach to therapy takes into account biological uniqueness of each patient at genome, transcriptome, and proteome levels, and is a priority area in molecular medicine. The identification of proteoforms, which have dramatic impact on the phenotype of a disease, is a fundamental task of personal molecular profiling. Considerable progress of proteomic approaches presented new avenues for accurate, specific, and high-performance protein analysis. Thus, the identification of new efficient bio-markers can be expected based on studies of aberrant proteoforms associated with various diseases.

[Multiomics study of HepG2 cell line proteome]. / Mul'tiomnaia strategiia issledovaniia proteoma kletochnoi linii gepatotselliuliarnoi kartsinomy HepG2.

Current proteomic studies are generally focused on the most abundant proteoforms encoded by canonical nucleic sequences. Transcriptomic and proteomic data, accumulated in a variety of postgenome sources and coupled with state-of-art analytical technologies, allow to start the identification of aberrant (non-canonical) proteoforms. The main sources of aberrant proteoforms are alternative splicing, single nucleotide polymorphism, and post-translational modifications. The aim of this work was to estimate the heterogeneity of HepG2 proteome. We suggested multiomics approach, which combines transcriptomic (RNAseq) and proteomic (2DE-MS/MS) methods, as a promising strategy to explore the proteome.

[Proteomic profiling of HaCaT keratinocytes exposed to skin damaging detergents]. / Proteomnoe profilirovanie keratinotsitov linii HaCaT pri vozdeistvii riada poverkhnostno-aktivnykh veshchestv, vyzyvaiushchikh povrezhdenie kozhi.

The effects of sodium dodecyl sulfate (25 mg/ml) and Triton X-100 (12.5 mg/ml and 25 mg/ml) on the HaCaT immortalized keratinocytes exposed to these surfactants for 48 h were studied. Using shotgun proteomics, a comparative analysis of the proteomic profiles of control and experimental cells after surfactants exposure was carried out. 260 common proteins were identified in control and experimental cells; 33 proteins were found in cells exposed to all three treatments, but not in control cells. These 33 proteins apparently reflect a nonspecific (universal) response of cells to toxic damage by the surfactants. These proteins are associated with activation of cell proliferation, changes in the functional activity of their ER and mitochondria, increased mRNA stability and activation of protein degradation processes in the cells. The possibility of using these proteins as a nonspecific parameter of cell response to cytotoxic damage is discussed. The mass spectrometry proteomics data ("raw", "mgf" and "xml" files) have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD007789 and PXD007776.

Changes in the Proteome of HaCaT Keratinocytes Induced by Cytotoxic Substance Triton X-100.

Changes in the proteome of keratinocytes of immortalized HaCaT line exposed to cytotoxic substance Triton X-100 in concentrations of 12.5 and 25 µg/ml were studied by liquid chromatography combined with mass spectrometry. The appearance of proteins involved in the regulation of mitosis, RNA stability, and catabolic processes were detected; the number of apoptosis-associated proteins increased, while the number of proteins involved in differentiation and energy metabolism of keratinocytes decreased.

[The Russian part of the human proteome project:first results and prospects].

The article summarizes the achievements of the pilot phase (2010-2014) of the Russian part of the international project "Human Proteome" and identifies the directions for further work on the study of the human chromosome 18 proteome in the framework of the project main phase (2015-2022). The pilot phase of the project was focused on the detection of at least one protein for each chromosome 18 protein-coding gene in three types of the biological material. The application of mass spectrometric detection of proteins by the methods of multiple reactions monitoring (MRM) and gene-centric approach made it possible to detect 95% of master forms of proteins, for 60% of which the quantitative assessment of the protein content was obtained in at least one type of the biological material. The task of the main phase of the project is to measure the proteome size of healthy individuals, taking into account the modified protein forms, providing for both the bioinformatics prediction of the quantity of proteins types and the selective experimental measurement of single proteoforms. Since the ranges of protein concentrations corresponding to the normal physiological state have not been identified, the work of the main phase of the project is focused on the study of clinically healthy individuals. The absence of these data complicates significantly the interpretation of the patients' blood proteomic profiles and prevents creating diagnostic tests. In the long term prospect, implementation of the project envisages development of a diagnostic test system based on multiple reactions monitoring (MRM) for quantitative measurement of the protein forms associated with some diseases. Development of such test systems will allow predicting the extent of risk of different diseases, diagnosing a disease at its early stage and monitoring the effectiveness of the treatment.

[Protocols of proteins interactomics: molecular fishing on optical chips and magnetic nanoparticles].

Now it is absolutely clear, that the majority of proteins in living systems function due to interaction with each other in stable or dynamic proteins complexes. Therefore necessity of deeper studies of proteins functions causes expansion of protein-protein interaction research. In the present review the brief description and comparative estimation of experimental methods and protocols of protein interactomics, based on technology of molecular fishing on an optical chips and paramagnetic nanoparticles is given.