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Bioinformatics of Genome Regulation and Structure–2026

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A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Informatics".

Deadline for manuscript submissions: 25 December 2026 | Viewed by 1225

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Prof. Dr. Yuriy L. Orlov

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Guest Editor

Center of Digital Health and AI in Medicine, Sechenov University, 119991 Moscow, Russia
Interests: bioinformatics; genomics; AI
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Prof. Dr. Nikolay A. Kolchanov

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Guest Editor

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Interests: bioinformatics; systems biology; genetics; genomics; gene networks
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Dr. Anastasia A. Anashkina

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Guest Editor

Laboratory of DNA-Protein Interactions, Engelhardt Institute of Molecular Biology of RAS, 119991 Moscow, Russia
Interests: structural bioinformatics; biophysics; bioinformatics
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Special Issue Information

Dear Colleagues,

This is a Special Issue collecting research manuscripts and reviews on genetics and bioinformatics on the topic of gene expression regulation from the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (ICG SB RAS) in Novosibirsk, Russia (https://www.icgbio.ru/), discussed at the “Bioinformatics of Genome Regulation and Structure/Systems Biology” (BGRS\SB) conference series (https://bgrssb.icgbio.ru/2026/en/). BGRS is a traditional biannual conference series in Novosibirsk that started in 1998 and which gathers scientists, bioinformaticians, medical doctors, AI specialists and geneticists. Gene expression regulation at the transcriptional level is a key topic of this journal issue.

We have organized several successful Special Issues on the bioinformatics of gene expression, including "Molecular Mechanisms of Gene Expression: “Bioinformatics of Gene Regulations and Structure”" (https://www.mdpi.com/journal/ijms/special_issues/Bioinformatics_Genomics) and "Bioinformatics of Gene Regulations and Structure-2025" (https://www.mdpi.com/journal/ijms/special_issues/3I56FG1O3A), as well as a series of topic issues on the medical applications of the bioinformatics of gene expression; see the links below.

In the research perspectives part of this Special Issue, we will focus on bioinformatics and systems biology approaches to genomics problems. The central problems include the analysis of the molecular mechanisms of gene expression regulation, the analysis of transcription regulation by protein transcription factors (TFs), regulatory gene network interaction analysis, and applications of AI tools in bioinformatics.

Topics of interest for this Special Issue include the following:

Analysis of gene expression regulation;
Applications of bioinformatics to omics technologies;
Non-coding RNA in gene expression regulation
Gene networks and associative network analysis;
Protein structure analysis and biophysical models;
Interdisciplinary research in computational genomics of model organisms—plants, animals, and bacteria;
Systems biology approaches for gene expression analysis, including machine learning and AI.

The BGRS conference series has its own history of initiating successful Special Issues on bioinformatics with IJMS:

Research on bioinformatics topics is in high demand at IJMS. We welcome novel research on bioinformatics education that extends the discussion beyond the frames of the BGRS conference series.

Prof. Dr. Yuriy L. Orlov
Prof. Dr. Nikolay A. Kolchanov
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-anonymized 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.

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Keywords

bioinformatics
genomics
human genetics
systems biology
AI
e-Health

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Research

28 pages, 4046 KB

Open AccessArticle

Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan

by Alexander V. Symonenko, Natalia V. Roshina, Olga Y. Rybina, Evgeniya A. Tsybul’ko, Anna V. Krementsova, Elena A. Mikhaleva, Vladimir E. Alatortsev, Dmitry V. Mukha and Elena G. Pasyukova

Int. J. Mol. Sci. 2026, 27(18), 8343; https://doi.org/10.3390/ijms27188343 (registering DOI) - 19 Sep 2026

Abstract

Revealing gene expression patterns is essential for comprehending the genetic control of complex traits like lifespan. Analyzing structural variation in gene regulatory regions within natural populations is a promising approach in functional genetics, allowing us to identify regulatory sites that influence transcription and phenotype in vivo. We describe the structural variability of the 5′ regulatory region of the shuttle craft (stc) gene in the Alexandrov population (Russia) of Drosophila melanogaster, encoding a transcription factor homologous to human NF-X1. We evaluated the association of frequently occurring polymorphisms with fly lifespan from inbred lines sampled in 2010, 2011, and 2014. Two polymorphisms in the stc 5′ regulatory region exhibit strong associations with both lifespan and embryonic stc transcript levels. Their role in expression regulation was evaluated via reporter gene assays conducted in S2 Drosophila cell culture. The ‘C’ allele at one polymorphic site and ‘T’ at the other are associated with increased longevity and decreased embryonic stc transcription, reaffirming the link between gene expression and lifespan we previously established. Furthermore, comparing stc 5′ regulatory region variability across Alexandrov, European and African populations suggests that the macro-geographic distribution of these longevity-associated variants is consistent with a potential role in latitudinal or climatic adaptation. Full article

(This article belongs to the Special Issue Bioinformatics of Genome Regulation and Structure–2026)

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16 pages, 1139 KB

Open AccessArticle

Insertion-Site Proximity to AAV Inverted Terminal Repeats Increases Plasmid Recombination

by Maxim Makarenko, Daria Semicheva and Veniamin Fishman

Int. J. Mol. Sci. 2026, 27(17), 7630; https://doi.org/10.3390/ijms27177630 - 26 Aug 2026

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Abstract

Adeno-associated virus (AAV)-based massively parallel reporter assays (MPRA) have become an important platform for large-scale functional characterization of regulatory DNA elements. However, plasmids carrying AAV inverted terminal repeats (ITRs) are intrinsically unstable during propagation in Escherichia coli, potentially compromising library integrity before viral packaging. Although ITR-associated recombination has been recognized, the influence of cloning-site position relative to the ITR on plasmid stability has not been systematically investigated. Here, we examined the relationship between cloning-junction proximity to AAV2 ITRs and plasmid recombination using an AAV-MPRA reporter plasmid. We compared four restriction-ligation cloning strategies utilizing restriction sites at defined distances (4–543 bp) from the nearest ITR while preserving ITR integrity, and one strategy in which the ITR itself was disrupted. We observe that plasmid recombination exhibited a pronounced distance dependence. Constructs with ligation junctions located 4, 41, and 182 bp from an intact ITR showed recombination frequencies of 82.5%, 60%, and 20%, respectively, whereas a 0% recombination frequency was detected when the nearest ITR was positioned 543 bp from the cloning junction. In contrast, cleavage within ITR reduced recombination to 15%, demonstrating that preservation of the intact ITR secondary structure is required for efficient recombination. Whole-plasmid sequencing confirmed recurrent large-scale deletions in which the expression cassette and the downstream R-ITR were removed while the L-ITR and plasmid backbone were retained, consistent with preferential processing of the intact L-ITR region. These findings identify cloning-site proximity to an intact AAV ITR as a major determinant of plasmid stability during bacterial propagation and demonstrate that substantial loss of correctly assembled constructs can occur before AAV production. The results have direct implications for the design of AAV-based MPRA libraries and support positioning cloning sites as far as practical from the nearest ITR, together with routine validation of plasmid integrity prior to viral packaging. Full article

(This article belongs to the Special Issue Bioinformatics of Genome Regulation and Structure–2026)

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19 pages, 3940 KB

Open AccessArticle

Non-Random Association of Ultraconserved Genomic Elements (UCE) with Human Genes

by Larisa Fedorova, Yuriy L. Orlov, Oleh A. Mulyar and Alexei Fedorov

Int. J. Mol. Sci. 2026, 27(16), 7214; https://doi.org/10.3390/ijms27167214 - 13 Aug 2026

Viewed by 402

Abstract

Ultraconserved elements (UCEs) are among the most evolutionarily conserved DNA sequences in vertebrate genomes, yet the biological mechanisms underlying their extraordinary conservation remain poorly understood. Using the recently developed dedUCE database comprising 12,813 human UCEs, we performed a comprehensive genome-wide analysis of their distribution relative to protein-coding genes, transcription factor (TF) genes, and long noncoding RNA (lncRNA) genes. UCEs showed a highly non-random genomic organization, with approximately 40% occurring in clusters within 20 kb genomic intervals. Non-KRAB transcription factor genes exhibited a striking sevenfold enrichment of UCEs compared with random expectation, whereas KRAB zinc-finger genes displayed an approximately tenfold depletion. Beyond TFs, UCE-rich genes were predominantly involved in developmental regulation, chromatin remodeling, RNA processing, and embryonic neurogenesis, whereas similarly large UCE-poor genes primarily encoded membrane proteins, ion channels, and synaptic components required for mature neuronal function. UCEs also demonstrated strong positional bias, with approximately fourfold enrichment near the 3′ ends of protein-coding genes but no comparable distribution pattern in lncRNAs. Although lncRNA genes showed only modest overall UCE enrichment, a small subset contained numerous UCEs. These findings demonstrate that UCEs preferentially associate with master developmental regulators rather than downstream neuronal effector genes, providing new insights into the functional organization and evolutionary conservation of the human genome. Full article

(This article belongs to the Special Issue Bioinformatics of Genome Regulation and Structure–2026)

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