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Multiomics Approaches in Biomedicine
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Multiomics Approaches in Biomedicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 17091

Special Issue Editor

Prof. Dr. Sergei Moshkovskii

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Guest Editor
1. Pirogov Russian National Research Medical University, 1, Ostrovityanova, 117997 Moscow, Russia
2. Federal Research and Clinical Center of Physical-Chemical Medicine, 1a, Malaya Pirogovskaya, 119435 Moscow, Russia
Interests: cancer proteomics; molecular biomarkers; proteogenomics; RNA editing; data processing in proteomics

Special Issue Information

Dear Colleagues,

The integration of high-throughput molecular data accompanies mass spectrometry-based proteomics from its very beginning. Up to now, the most efficient mode of proteome profiling was based on a search with the use of genomic sequence for the corresponding species. Since proteomics was able to quantify thousands of gene products, integration of transcriptome and proteome data became feasible, which provided new possibilities for system description and modelling of cellular processes. Furthermore, routine use of high-resolution mass spectrometry in proteomics made it possible to study the production of protein-coding genomic variants at the proteome level, which is especially important in cancer research, where mutations serve as drivers of malignant transformation. Integration of omics data for nucleic acids and proteins, called, sensu lato, proteogenomics, turned into a valuable instrument for biomedical research. Instruments and applications of proteogenomics are to be collected in the Special Issue.

Omics techniques that describe gene expression are currently taking the first steps towards single-cell resolution, and single-cell proteomics follows a fast growing transcriptomic approach. Thus, the cell proteogenomics is headlined with a perspective of single-cell data integration, which is not yet possible.

For this Special Issue, we invite authors to contribute original research articles, method papers, as well as review articles that will address recent developments in the area of proteogenomics in the broad sense of this term.

Potential topics include, but are not limited to, the following:

New methods of genomic, transcriptomic, and proteomic data integration;

multi-omics quantitative analysis of cellular mechanisms;

identification and functional analysis of genomic variants and mutations, particularly in cancer proteomes;

proteome recoding by post-transcriptional modifications, such as RNA editing;

genome reannotation using proteomic data;

proteomics for identification of neo-antigens;

identification and functional analysis of short open reading frames and their microproteins.

Prof. Dr. Sergei Moshkovskii
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proteogenomics
  • multi-omics
  • proteome
  • mass-spectrometry
  • transcriptome
  • mutation
  • cancer genome
  • RNA editing
  • post-transcriptional modification

Published Papers (6 papers)

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Research

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12 pages, 2241 KiB  
Article
Differential Impact of Hexuronate Regulators ExuR and UxuR on the Escherichia coli Proteome
by Tatiana A. Bessonova, Maria S. Fando, Olga S. Kostareva, Maria N. Tutukina, Olga N. Ozoline, Mikhail S. Gelfand, Alexey D. Nikulin and Svetlana V. Tishchenko
Int. J. Mol. Sci. 2022, 23(15), 8379; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158379 - 29 Jul 2022
Cited by 1 | Viewed by 1429
Abstract
ExuR and UxuR are paralogous proteins belonging to the GntR family of transcriptional regulators. Both are known to control hexuronic acid metabolism in a variety of Gammaproteobacteria but the relative impact of each of them is still unclear. Here, we apply 2D difference [...] Read more.
ExuR and UxuR are paralogous proteins belonging to the GntR family of transcriptional regulators. Both are known to control hexuronic acid metabolism in a variety of Gammaproteobacteria but the relative impact of each of them is still unclear. Here, we apply 2D difference electrophoresis followed by mass-spectrometry to characterise the changes in the Escherichia coli proteome in response to a uxuR or exuR deletion. Our data clearly show that the effects are different: deletion of uxuR resulted in strongly enhanced expression of D-mannonate dehydratase UxuA and flagellar protein FliC, and in a reduced amount of outer membrane porin OmpF, while the absence of ExuR did not significantly alter the spectrum of detected proteins. Consequently, the physiological roles of proteins predicted as homologs seem to be far from identical. Effects of uxuR deletion were largely dependent on the cultivation conditions: during growth with glucose, UxuA and FliC were dramatically altered, while during growth with glucuronate, activation of both was not so prominent. During the growth with glucose, maximal activation was detected for FliC. This was further confirmed by expression analysis and physiological tests, thus suggesting the involvement of UxuR in the regulation of bacterial motility and biofilm formation. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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20 pages, 3297 KiB  
Article
Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus
by Anastasia S. Nikitina, Anastasia V. Lipatova, Anton O. Goncharov, Anna A. Kliuchnikova, Mikhail A. Pyatnitskiy, Ksenia G. Kuznetsova, Azzam Hamad, Pavel O. Vorobyev, Olga N. Alekseeva, Marah Mahmoud, Yasmin Shakiba, Ksenia S. Anufrieva, Georgy P. Arapidi, Mark V. Ivanov, Irina A. Tarasova, Mikhail V. Gorshkov, Peter M. Chumakov and Sergei A. Moshkovskii
Int. J. Mol. Sci. 2022, 23(9), 5244; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095244 - 08 May 2022
Cited by 3 | Viewed by 2651
Abstract
Cancer cell lines responded differentially to type I interferon treatment in models of oncolytic therapy using vesicular stomatitis virus (VSV). Two opposite cases were considered in this study, glioblastoma DBTRG-05MG and osteosarcoma HOS cell lines exhibiting resistance and sensitivity to VSV after the [...] Read more.
Cancer cell lines responded differentially to type I interferon treatment in models of oncolytic therapy using vesicular stomatitis virus (VSV). Two opposite cases were considered in this study, glioblastoma DBTRG-05MG and osteosarcoma HOS cell lines exhibiting resistance and sensitivity to VSV after the treatment, respectively. Type I interferon responses were compared for these cell lines by integrative analysis of the transcriptome, proteome, and RNA editome to identify molecular factors determining differential effects observed. Adenosine-to-inosine RNA editing was equally induced in both cell lines. However, transcriptome analysis showed that the number of differentially expressed genes was much higher in DBTRG-05MG with a specific enrichment in inflammatory proteins. Further, it was found that two genes, EGFR and HER2, were overexpressed in HOS cells compared with DBTRG-05MG, supporting recent reports that EGF receptor signaling attenuates interferon responses via HER2 co-receptor activity. Accordingly, combined treatment of cells with EGF receptor inhibitors such as gefitinib and type I interferon increases the resistance of sensitive cell lines to VSV. Moreover, sensitive cell lines had increased levels of HER2 protein compared with non-sensitive DBTRG-05MG. Presumably, the level of this protein expression in tumor cells might be a predictive biomarker of their resistance to oncolytic viral therapy. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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26 pages, 41215 KiB  
Article
Better Agreement of Human Transcriptomic and Proteomic Cancer Expression Data at the Molecular Pathway Activation Level
by Mikhail Raevskiy, Maxim Sorokin, Galina Zakharova, Victor Tkachev, Nicolas Borisov, Denis Kuzmin, Kristina Kremenchutckaya, Alexander Gudkov, Dmitry Kamashev and Anton Buzdin
Int. J. Mol. Sci. 2022, 23(5), 2611; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052611 - 26 Feb 2022
Cited by 5 | Viewed by 2038
Abstract
Previously, we have shown that the aggregation of RNA-level gene expression profiles into quantitative molecular pathway activation metrics results in lesser batch effects and better agreement between different experimental platforms. Here, we investigate whether pathway level of data analysis provides any advantage when [...] Read more.
Previously, we have shown that the aggregation of RNA-level gene expression profiles into quantitative molecular pathway activation metrics results in lesser batch effects and better agreement between different experimental platforms. Here, we investigate whether pathway level of data analysis provides any advantage when comparing transcriptomic and proteomic data. We compare the paired proteomic and transcriptomic gene expression and pathway activation profiles obtained for the same human cancer biosamples in The Cancer Genome Atlas (TCGA) and the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) projects, for a total of 755 samples of glioblastoma, breast, liver, lung, ovarian, pancreatic, and uterine cancers. In a CPTAC assay, expression levels of 15,112 protein-coding genes were profiled using the Thermo QE series of mass spectrometers. In TCGA, RNA expression levels of the same genes were obtained using the Illumina HiSeq 4000 engine for the same biosamples. At the gene level, absolute gene expression values are compared, whereas pathway-grade comparisons are made between the pathway activation levels (PALs) calculated using average sample-normalized transcriptomic and proteomic profiles. We observed remarkably different average correlations between the primary RNA- and protein expression data for different cancer types: Spearman Rho between 0.017 (p = 1.7 × 10−13) and 0.27 (p < 2.2 × 10−16). However, at the pathway level we detected overall statistically significantly higher correlations: averaged Rho between 0.022 (p < 2.2 × 10−16) and 0.56 (p < 2.2 × 10−16). Thus, we conclude that data analysis at the PAL-level yields results of a greater similarity when comparing high-throughput RNA and protein expression profiles. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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12 pages, 1238 KiB  
Article
The Effect of Meclofenoxate on the Transcriptome of Aging Brain of Nothobranchius guentheri Annual Killifish
by Ildar R. Bakhtogarimov, Anna V. Kudryavtseva, George S. Krasnov, Natalya S. Gladysh, Vsevolod V. Volodin, Alexander A. Kudryavtsev, Elizaveta V. Bulavkina, Margarita A. Goncharova, Veronika S. Ledyaeva, Ivan S. Pastukhov, Yulia S. Vershinina, Anna M. Starkova, Anastasiya V. Snezhkina, Anastasija I. Shuvalova, Vladislav S. Pavlov, Dmitry L. Nikiforov-Nikishin, Alexey A. Moskalev and Zulfiya G. Guvatova
Int. J. Mol. Sci. 2022, 23(5), 2491; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052491 - 24 Feb 2022
Cited by 3 | Viewed by 2805
Abstract
Annual fish of the genus Nothobranchius are promising models for aging research. Nothobranchius reproduces typical aspects of vertebrate aging, including hallmarks of brain aging. Meclofenoxate (MF) is a well-known compound that can enhance cognitive performance. The drug is prescribed for asthenic conditions, trauma, [...] Read more.
Annual fish of the genus Nothobranchius are promising models for aging research. Nothobranchius reproduces typical aspects of vertebrate aging, including hallmarks of brain aging. Meclofenoxate (MF) is a well-known compound that can enhance cognitive performance. The drug is prescribed for asthenic conditions, trauma, and vascular diseases of the brain. It is believed that MF is able to delay age-dependent changes in the human brain. However, until now, there has been no study of the MF effect on the brain transcriptome. In the present work, we performed an RNA-Seq study of brain tissues from aged Nothobranchius guentheri, which were almost lifetime administered with MF, as well as young and aged control fish. As expected, in response to MF, we revealed significant overexpression of neuron-specific genes including genes involved in synaptic activity and plasticity, neurotransmitter secretion, and neuron projection. The effect was more pronounced in female fish. In this aspect, MF alleviated age-dependent decreased expression of genes involved in neuronal activity. In both treated and untreated animals, we observed strong aging-associated overexpression of immune and inflammatory response genes. MF treatment did not prevent this effect, and moreover, some of these genes tended to be slightly upregulated under MF treatment. Additionally, we noticed upregulation of some genes associated with aging and cellular senescence, including isoforms of putative vascular cell adhesion molecule 1 (VCAM1), protein O-GlcNAcase (OGA), protein kinase C alpha type (KPCA), prolow-density lipoprotein receptor-related protein 1 (LRP1). Noteworthy, MF treatment was also associated with the elevated transcription of transposons, which are highly abundant in the N. guentheri genome. In conclusion, MF compensates for the age-dependent downregulation of neuronal activity genes, but its effect on aging brain transcriptome still cannot be considered unambiguously positive. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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Review

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17 pages, 1879 KiB  
Review
Interplay between A-to-I Editing and Splicing of RNA: A Potential Point of Application for Cancer Therapy
by Anton O. Goncharov, Victoria O. Shender, Ksenia G. Kuznetsova, Anna A. Kliuchnikova and Sergei A. Moshkovskii
Int. J. Mol. Sci. 2022, 23(9), 5240; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095240 - 08 May 2022
Cited by 8 | Viewed by 2981
Abstract
Adenosine-to-inosine RNA editing is a system of post-transcriptional modification widely distributed in metazoans which is catalyzed by ADAR enzymes and occurs mostly in double-stranded RNA (dsRNA) before splicing. This type of RNA editing changes the genetic code, as inosine generally pairs with cytosine [...] Read more.
Adenosine-to-inosine RNA editing is a system of post-transcriptional modification widely distributed in metazoans which is catalyzed by ADAR enzymes and occurs mostly in double-stranded RNA (dsRNA) before splicing. This type of RNA editing changes the genetic code, as inosine generally pairs with cytosine in contrast to adenosine, and this expectably modulates RNA splicing. We review the interconnections between RNA editing and splicing in the context of human cancer. The editing of transcripts may have various effects on splicing, and resultant alternatively spliced isoforms may be either tumor-suppressive or oncogenic. Dysregulated RNA splicing in cancer often causes the release of excess amounts of dsRNA into cytosol, where specific dsRNA sensors provoke antiviral-like responses, including type I interferon signaling. These responses may arrest cell division, causing apoptosis and, externally, stimulate antitumor immunity. Thus, small-molecule spliceosome inhibitors have been shown to facilitate the antiviral-like signaling and are considered to be potential cancer therapies. In turn, a cytoplasmic isoform of ADAR can deaminate dsRNA in cytosol, thereby decreasing its levels and diminishing antitumor innate immunity. We propose that complete or partial inhibition of ADAR may enhance the proapoptotic and cytotoxic effects of splicing inhibitors and that it may be considered a promising addition to cancer therapies targeting RNA splicing. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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20 pages, 1253 KiB  
Review
Progress in Methods for Copy Number Variation Profiling
by Veronika Gordeeva, Elena Sharova and Georgij Arapidi
Int. J. Mol. Sci. 2022, 23(4), 2143; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042143 - 15 Feb 2022
Cited by 7 | Viewed by 4066
Abstract
Copy number variations (CNVs) are the predominant class of structural genomic variations involved in the processes of evolutionary adaptation, genomic disorders, and disease progression. Compared with single-nucleotide variants, there have been challenges associated with the detection of CNVs owing to their diverse sizes. [...] Read more.
Copy number variations (CNVs) are the predominant class of structural genomic variations involved in the processes of evolutionary adaptation, genomic disorders, and disease progression. Compared with single-nucleotide variants, there have been challenges associated with the detection of CNVs owing to their diverse sizes. However, the field has seen significant progress in the past 20–30 years. This has been made possible due to the rapid development of molecular diagnostic methods which ensure a more detailed view of the genome structure, further complemented by recent advances in computational methods. Here, we review the major approaches that have been used to routinely detect CNVs, ranging from cytogenetics to the latest sequencing technologies, and then cover their specific features. Full article
(This article belongs to the Special Issue Multiomics Approaches in Biomedicine)
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