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Molecular Mechanisms of Gene Expression: “Bioinformatics of Gene Regulations and Structure”

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

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 28448

Special Issue Editors

The Digital Health Institute, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia
Interests: computer genomics; bioinformatics; digital medicine (e-Health); gene expression regulation; ChIP-seq
Special Issues, Collections and Topics in MDPI journals
University of La Verne, La Verne, CA, USA
Interests: medical genomics; population genetics; plant genetics; bioinformatics
Special Issues, Collections and Topics in MDPI journals
1. Engelhardt Institute of Molecular Biology RAS, 119991 Moscow, Russia
2. The Digital Health Institute, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia
Interests: structural bioinformatics; biophysics; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special issue, which shall collect papers on genomics in biomedicine and biotechnology, is based on the materials presented at “Bioinformatics of Genome Regulation and Structure/Systems Biology” (BGRS\SB-2020) Multi-Conference 6–10 July, in Novosibirsk, Russia (https://bgrssb.icgbio.ru/2020/). BGRS is a traditional biannual conference series in Novosibirsk which started in 1998 and which gathers scientists, bioinformaticians, medical doctors, and geneticists. This IJMS Special Issue shall continue the thematic collection of recent advances in medical genetics and bioinformatics following the recent human population genetics conference in Moscow
https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/Medical_Genetics_Bioinformatics

Here, we focus on bioinformatics and systems biology approaches to genomics and biotechnology problems. The central problem is that analysis of gene expression regulations, bioinformatics of regulatory molecular mechanisms and network interaction underlying gene function manifestation.

Topics of the Special Issue include:

  • Genomics and omics technology applications;
  • Medical genetics;
  • Gene networks in diseases;
  • Interdisciplinary research in genomics of model organisms;
  • Genomics and systems biology.

We welcome novel materials beyond the conference discussion.

Prof. Dr. Yuriy L Orlov
Prof. Dr. Tatiana V. Tatarinova
Dr. Anastasia A. Anashkina
Guest Editors

Manuscript Submission Information

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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

  • Bioinformatics
  • Systems biology
  • Human genomics
  • Computational plant genomics
  • Genomics of model organisms
  • Gene expression regulation
  • Fundamental biomedicine
  • Gene networks

Published Papers (10 papers)

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Editorial

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4 pages, 209 KiB  
Editorial
Bioinformatics Applications to Reveal Molecular Mechanisms of Gene Expression Regulation in Model Organisms
by Yuriy L. Orlov, Tatiana V. Tatarinova and Anastasia A. Anashkina
Int. J. Mol. Sci. 2021, 22(21), 11973; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111973 - 05 Nov 2021
Cited by 7 | Viewed by 1808
Abstract
Gene expression regulation at the transcriptome, genome, cell, and tissue levels is a complex phenomenon demanding the development of bioinformatics tools [...] Full article

Research

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19 pages, 16715 KiB  
Article
Comparative Transcriptomes of the Body Wall of Wild and Farmed Sea Cucumber Isostichopus badionotus
by Roberto Martín-Hernández, Rossanna Rodríguez-Canul, Nuvia Kantún-Moreno, Miguel A. Olvera-Novoa, Oscar Medina-Contreras, Cristobal Garikoitz-Legarda, Juan Carlos Triviño, Jesús Alejandro Zamora-Briseño, Víctor May-Solis, Alicia Poot-Salazar, Juan Antonio Pérez-Vega, Judit Gil-Zamorano, George Grant, Alberto Dávalos and Leticia Olivera-Castillo
Int. J. Mol. Sci. 2021, 22(8), 3882; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083882 - 09 Apr 2021
Cited by 2 | Viewed by 2699
Abstract
Overfishing of sea cucumber Isostichopus badionotus from Yucatan has led to a major population decline. They are being captured as an alternative to traditional species despite a paucity of information about their health-promoting properties. The transcriptome of the body wall of wild and [...] Read more.
Overfishing of sea cucumber Isostichopus badionotus from Yucatan has led to a major population decline. They are being captured as an alternative to traditional species despite a paucity of information about their health-promoting properties. The transcriptome of the body wall of wild and farmed I. badionotus has now been studied for the first time by an RNA-Seq approach. The functional profile of wild I. badionotus was comparable with data in the literature for other regularly captured species. In contrast, the metabolism of first generation farmed I. badionotus was impaired. This had multiple possible causes including a sub-optimal growth environment and impaired nutrient utilization. Several key metabolic pathways that are important in effective handling and accretion of nutrients and energy, or clearance of harmful cellular metabolites, were disrupted or dysregulated. For instance, collagen mRNAs were greatly reduced and deposition of collagen proteins impaired. Wild I. badionotus is, therefore, a suitable alternative to other widely used species but, at present, the potential of farmed I. badionotus is unclear. The environmental or nutritional factors responsible for their impaired function in culture remain unknown, but the present data gives useful pointers to the underlying problems associated with their aquaculture. Full article
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14 pages, 729 KiB  
Article
Somatic Copy Number Alterations and Associated Genes in Clear-Cell Renal-Cell Carcinoma in Brazilian Patients
by Flávia Gonçalves Fernandes, Henrique Cesar Santejo Silveira, João Neif Antonio Júnior, Rosana Antunes da Silveira, Luis Eduardo Zucca, Flavio Mavignier Cárcano, André Octavio Nicolau Sanches, Luciano Neder, Cristovam Scapulatempo-Neto, Sergio Vicente Serrano, Eric Jonasch, Rui Manuel Reis and Adriane Feijó Evangelista
Int. J. Mol. Sci. 2021, 22(5), 2265; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052265 - 25 Feb 2021
Cited by 12 | Viewed by 2468
Abstract
Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some [...] Read more.
Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some of these regional CNAs are suspected of altering gene expression and could influence clinical outcomes. Despite many studies of CNAs in RCC, there are currently no descriptions of genomic copy number alterations in a Brazilian ccRCC cohort. This study was designed to evaluate the chromosomal profile of CNAs in Brazilian ccRCC tumors and explore clinical associations. A total of 92 ccRCC Brazilian patients that underwent nephrectomy at Barretos Cancer Hospital were analyzed for CNAs by array comparative genomic hybridization. Most patients in the cohort had early-stage localized disease. The most significant alterations were loss of 3p (87.3%), 14q (35.8%), 6q (29.3%), 9p (28.6%) and 10q (25.0%), and gains of 5q (59.7%), 7p (29.3%) and 16q (20.6%). Bioinformatics analysis revealed 19 genes mapping to CNA significant regions, including SETD2, BAP1, FLT4, PTEN, FGFR4 and NSD1. Moreover, gain of 5q34-q35.3 (FLT4 and NSD1) and loss of 6q23.2-q23.3 (MYB) and 9p21.3 (MLLT3) had gene expression levels that correlated with TCGA data and was also associated with advanced disease features, such as larger tumors, Fuhrman 3, metastasis at diagnosis and death. The loss of region 14q22.1 which encompasses the NIN gene was associated with poor overall survival. Overall, this study provides the first CNA landscape of Brazilian patients and pinpoints genomic regions and specific genes worthy of more detailed investigations. Our results highlight important genes that are associated with copy number changes involving large chromosomal regions that are potentially related to ccRCC tumorigenesis and disease biology for future clinical investigations. Full article
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14 pages, 2540 KiB  
Article
Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events
by Frida Belinky, Ishan Ganguly, Eugenia Poliakov, Vyacheslav Yurchenko and Igor B. Rogozin
Int. J. Mol. Sci. 2021, 22(4), 1876; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041876 - 14 Feb 2021
Cited by 5 | Viewed by 2293
Abstract
Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons [...] Read more.
Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels. Full article
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15 pages, 3527 KiB  
Article
Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
by Xiaomin Zhang, Fathima S. Ameer, Gohar Azhar and Jeanne Y. Wei
Int. J. Mol. Sci. 2021, 22(2), 473; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020473 - 06 Jan 2021
Cited by 13 | Viewed by 3231
Abstract
Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on the [...] Read more.
Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on the sirtuin genes. Here, we report the identification of 23 human sirtuin isoforms, most of which were not previously reported. Five of the sirtuin genes had more than one isoform, whereas sirtuin-6 had nine isoforms. Exon skipping was the main event. Most of the sirtuin isoforms were deficient in parts of the protein domains, including the catalytic domain, the N- or C-terminus, nuclear localization signal or mitochondrial targeting signal. The domain loss caused potential structural changes. Three SIRT1 isoforms had a differential effect on the mitochondrial oxygen consumption rate. Age-related changes in the expression of SIRT1 isoforms were observed in the human heart in fetus, adults, and very old individuals. We also identified 15 sirtuin isoforms in mice. Our data indicate that alternative splicing increases sirtuin gene diversity and may modulate subcellular localization and function, thereby adding complexity to the gene regulation of mitochondrial respiration, metabolism, and cardiac function during maturation and aging. Full article
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17 pages, 4097 KiB  
Article
Whole-Transcriptome Sequencing-Based Analysis of DAZL and Its Interacting Genes during Germ Cells Specification and Zygotic Genome Activation in Chickens
by Deivendran Rengaraj, Sohyoung Won, Jong Won Han, DongAhn Yoo, Heebal Kim and Jae Yong Han
Int. J. Mol. Sci. 2020, 21(21), 8170; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218170 - 31 Oct 2020
Cited by 6 | Viewed by 2203
Abstract
The deleted in azoospermia like (DAZL) is required for germ cells development and maintenance. In chickens, the mRNA and protein of DAZL, a representative maternally inherited germ plasm factor, are detected in the germ plasm of oocyte, zygote, and all [...] Read more.
The deleted in azoospermia like (DAZL) is required for germ cells development and maintenance. In chickens, the mRNA and protein of DAZL, a representative maternally inherited germ plasm factor, are detected in the germ plasm of oocyte, zygote, and all stages of the intrauterine embryos. However, it is still insufficient to explain the origin and specification process of chicken germ cells, because the stage at which the zygotic transcription of DAZL occurs and the stage at which the maternal DAZL RNA/protein clears have not yet been fully identified. Moreover, a comprehensive understanding of the expression of DAZL interacting genes during the germ cells specification and development and zygotic genome activation (ZGA) is lacking in chickens. In this study, we identified a set of DAZL interacting genes in chickens using in silico prediction method. Then, we analyzed the whole-transcriptome sequencing (WTS)-based expression of DAZL and its interacting genes in the chicken oocyte, zygote, and Eyal-Giladi and Kochav (EGK) stage embryos (EGK.I to EGK.X). In the results, DAZL transcripts are increased in the zygote (onset of transcription), maintained the increased level until EGK.VI, and decreased from EGK.VIII (possible clearance of maternal RNAs). Among the DAZL interacting genes, most of them are increased either at 1st ZGA or 2nd ZGA, indicating their involvement in germ cells specification and development. Full article
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13 pages, 1843 KiB  
Article
Cooperative Interaction of Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02 in the Diseased Sponge Lubomirskia baicalensis
by Ivan Petrushin, Sergei Belikov and Lubov Chernogor
Int. J. Mol. Sci. 2020, 21(21), 8128; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218128 - 30 Oct 2020
Cited by 6 | Viewed by 2223
Abstract
Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a [...] Read more.
Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a significant problem in Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria from the families Flavobacteriaceae and Oxalobacteraceae dominate the microbiomes of diseased sponges. Both species are opportunistic pathogens common in freshwater ecosystems. The aim of our study was to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. Janthinobacterium sp. SLB01 attacks other cells using a type VI secretion system and suppresses gram-positive bacteria with violacein, and regulates its own activity via quorum sensing. It produces floc and strong biofilm by exopolysaccharide biosynthesis and PEP-CTERM/XrtA protein expression. Flavobacterium sp. SLB02 utilizes the fragments of cell walls produced by polysaccharides. These two strains have a marked difference in carbohydrate acquisition. We described a possible means of joint occupation of the ecological niche in the freshwater sponge microbial community. This study expands the understanding of the symbiotic relationship of microorganisms with freshwater Baikal sponges. Full article
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14 pages, 1915 KiB  
Article
Predicting FOXM1-Mediated Gene Regulation through the Analysis of Genome-Wide FOXM1 Binding Sites in MCF-7, K562, SK-N-SH, GM12878 and ECC-1 Cell Lines
by Keunsoo Kang, Yoonjung Choi, Hoo Hyun Kim, Kyung Hyun Yoo and Sungryul Yu
Int. J. Mol. Sci. 2020, 21(17), 6141; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176141 - 26 Aug 2020
Cited by 11 | Viewed by 3802
Abstract
Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. However, the mechanism by which FOXM1 controls the common gene set in different cellular contexts is [...] Read more.
Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. However, the mechanism by which FOXM1 controls the common gene set in different cellular contexts is unclear. In this study, a comprehensive meta-analysis of genome-wide FOXM1 binding sites in ECC-1, GM12878, K562, MCF-7, and SK-N-SH cell lines was conducted to predict FOXM1-driven gene regulation. Consistent with previous studies, different TF binding motifs were identified at FOXM1 binding sites, while the NFY binding motif was found at 81% of common FOXM1 binding sites in promoters of cell cycle-related genes. The results indicated that FOXM1 might control the gene set through interaction with the NFY proteins, while cell type-specific genes were predicted to be regulated by enhancers with FOXM1 and cell type-specific TFs. We also found that the high expression level of FOXM1 was significantly associated with poor prognosis in nine types of cancer. Overall, these results suggest that FOXM1 is predicted to function as a master regulator of the cell cycle through the interaction of NFY-family proteins, and therefore the inhibition of FOXM1 could be an attractive strategy for cancer therapy. Full article
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22 pages, 3964 KiB  
Article
Asymmetric Conservation within Pairs of Co-Occurred Motifs Mediates Weak Direct Binding of Transcription Factors in ChIP-Seq Data
by Victor Levitsky, Dmitry Oshchepkov, Elena Zemlyanskaya and Tatyana Merkulova
Int. J. Mol. Sci. 2020, 21(17), 6023; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176023 - 21 Aug 2020
Cited by 5 | Viewed by 2568
Abstract
(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. [...] Read more.
(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. (2) Methods: We applied the motifs co-occurrence tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for the prediction of asymmetric CEs with one of the participating motifs possessing higher conservation than another does. (3) Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from the ETS (E26 Transformation Specific) family. (4) Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq. Full article
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Review

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30 pages, 752 KiB  
Review
Genomics of Human Fibrotic Diseases: Disordered Wound Healing Response
by Rivka C. Stone, Vivien Chen, Jamie Burgess, Sukhmani Pannu and Marjana Tomic-Canic
Int. J. Mol. Sci. 2020, 21(22), 8590; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228590 - 14 Nov 2020
Cited by 17 | Viewed by 3830
Abstract
Fibrotic disease, which is implicated in almost half of all deaths worldwide, is the result of an uncontrolled wound healing response to injury in which tissue is replaced by deposition of excess extracellular matrix, leading to fibrosis and loss of organ function. A [...] Read more.
Fibrotic disease, which is implicated in almost half of all deaths worldwide, is the result of an uncontrolled wound healing response to injury in which tissue is replaced by deposition of excess extracellular matrix, leading to fibrosis and loss of organ function. A plethora of genome-wide association studies, microarrays, exome sequencing studies, DNA methylation arrays, next-generation sequencing, and profiling of noncoding RNAs have been performed in patient-derived fibrotic tissue, with the shared goal of utilizing genomics to identify the transcriptional networks and biological pathways underlying the development of fibrotic diseases. In this review, we discuss fibrosing disorders of the skin, liver, kidney, lung, and heart, systematically (1) characterizing the initial acute injury that drives unresolved inflammation, (2) identifying genomic studies that have defined the pathologic gene changes leading to excess matrix deposition and fibrogenesis, and (3) summarizing therapies targeting pro-fibrotic genes and networks identified in the genomic studies. Ultimately, successful bench-to-bedside translation of observations from genomic studies will result in the development of novel anti-fibrotic therapeutics that improve functional quality of life for patients and decrease mortality from fibrotic diseases. Full article
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