Reconstruction and Analysis of Gene Networks of Human Neurotransmitter Systems Reveal Genes with Contentious Manifestation for Anxiety, Depression, and Intellectual Disabilities

Background: The study of the biological basis of anxiety, depression, and intellectual disabilities in humans is one of the most actual problems of modern neurophysiology. Of particular interest is the study of complex interactions between molecular genetic factors, electrophysiological properties of the nervous system, and the behavioral characteristics of people. The neurobiological understanding of neuropsychiatric disorders requires not only the identification of genes that play a role in the molecular mechanisms of the occurrence and course of diseases, but also the understanding of complex interactions that occur between these genes. A systematic study of such interactions obviously contributes to the development of new methods of diagnosis, prevention, and treatment of disorders, as the orientation to allele variants of individual loci is not reliable enough, because the literature describes a number of genes, the same alleles of which can be associated with different, sometimes extremely different variants of phenotypic traits, depending on the genetic background, of their carriers, habitat, and other factors. Results: In our study, we have reconstructed a series of gene networks (in the form of protein–protein interactions networks, as well as networks of transcription regulation) to build a model of the influence of complex interactions of environmental factors and genetic risk factors for intellectual disability, depression, and other disorders in human behavior. Conclusion: A list of candidate genes whose expression is presumably associated with environmental factors and has potentially contentious manifestation for behavioral and neurological traits is identified for further experimental verification.

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Search for New Candidate Genes Involved in the Comorbidity of Asthma and Hypertension Based on Automatic Analysis of Scientific Literature

Journal of Integrative Bioinformatics ◽

10.1515/jib-2018-0054 ◽

2018 ◽

Vol 15 (4) ◽

Cited By ~ 1

Author(s):

Olga V. Saik ◽

Pavel S. Demenkov ◽

Timofey V. Ivanisenko ◽

Elena Yu. Bragina ◽

Maxim B. Freidin ◽

...

Keyword(s):

Protein Interactions ◽

Gene Networks ◽

Molecular Mechanisms ◽

Molecular Genetic ◽

Genetic Networks ◽

Positive Sign ◽

Phenotypic Traits ◽

Protein Protein Interactions ◽

Scientific Publications ◽

Associative Gene Networks

AbstractComorbid states of diseases significantly complicate diagnosis and treatment. Molecular mechanisms of comorbid states of asthma and hypertension are still poorly understood. Prioritization is a way for identifying genes involved in complex phenotypic traits. Existing methods of prioritization consider genetic, expression and evolutionary data, molecular-genetic networks and other. In the case of molecular-genetic networks, as a rule, protein-protein interactions and KEGG networks are used. ANDSystem allows reconstructing associative gene networks, which include more than 20 types of interactions, including protein-protein interactions, expression regulation, transport, catalysis, etc. In this work, a set of genes has been prioritized to find genes potentially involved in asthma and hypertension comorbidity. The prioritization was carried out using well-known methods (ToppGene and Endeavor) and a cross-talk centrality criterion, calculated by analysis of associative gene networks from ANDSystem. The identified genes, including IL1A, CD40LG, STAT3, IL15, FAS, APP, TLR2, C3, IL13 and CXCL10, may be involved in the molecular mechanisms of comorbid asthma/hypertension. An analysis of the dynamics of the frequency of mentioning the most priority genes in scientific publications revealed that the top 100 priority genes are significantly enriched with genes with increased positive dynamics, which may be a positive sign for further studies of these genes.

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Novel Comprehensive Bioinformatics Approaches to Determine the Molecular Genetic Susceptibility Profile of Moderate and Severe Asthma

International Journal of Molecular Sciences ◽

10.3390/ijms21114022 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4022

Author(s):

Hatem Zayed

Keyword(s):

Severe Asthma ◽

Protein Interactions ◽

Gene Networks ◽

Molecular Genetic ◽

Enrichment Analysis ◽

Protein Protein Interactions ◽

Bioinformatics Pipeline ◽

Moderate Asthma ◽

Asthma Phenotypes ◽

Chronic Inflammatory Condition

Background: Asthma is a chronic inflammatory condition linked to hyperresponsiveness in the airways. There is currently no cure available for asthma, and therapy choices are limited. Asthma is the result of the interplay between genes and the environment. The exact molecular genetic mechanism of asthma remains elusive. Aims: The aim of this study is to provide a comprehensive, detailed molecular etiology profile for the molecular factors that regulate the severity of asthma and pathogenicity using integrative bioinformatics tools. Methods: The GSE43696 omnibus gene expression dataset, which contains 50 moderate cases, 38 severe cases, and 20 healthy controls, was used to investigate differentially expressed genes (DEGs), susceptible chromosomal loci, gene networks, pathways, gene ontologies, and protein–protein interactions (PPIs) using an intensive bioinformatics pipeline. Results: The PPI network analysis yielded DEGs that contribute to interactions that differ from moderate-to-severe asthma. The combined interaction scores resulted in higher interactions for the genes STAT3, AGO2, COL1A1, CLCN6, and KSR for moderate asthma and JAK2, INSR, ERBB2, NR3C1, and PTK6 for severe asthma. Enrichment analysis (EA) demonstrated differential enrichment between moderate and severe asthma phenotypes; the ion transport regulation pathway was significantly enhanced in severe asthma phenotypes compared to that in moderate asthma phenotypes and involved PER2, GCR, IRS-2, KCNK7, KCNK6, NOX1, and SCN7A. The most enriched common pathway in both moderate and severe asthma is the development of the glucocorticoid receptor (GR) signaling pathway followed by glucocorticoid-mediated inhibition of proinflammatory and proconstrictory signaling in the airway of smooth muscle cell pathways. Gene sets were shared between severe and moderate asthma at 16 chromosome locations, including 17p13.1, 16p11.2, 17q21.31, 1p36, and 19q13.2, while 60 and 48 chromosomal locations were unique for both moderate and severe asthma, respectively. Phylogenetic analysis for DEGs showed that several genes have been intersected in phases of asthma in the same cluster of genes. This could indicate that several asthma-associated genes have a common ancestor and could be linked to the same biological function or gene family, implying the importance of these genes in the pathogenesis of asthma. Conclusion: New genetic risk factors for the development of moderate-to-severe asthma were identified in this study, and these could provide a better understanding of the molecular pathology of asthma and might provide a platform for the treatment of asthma.

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Seizure Semiology, Neurotransmitter Receptors and Cellular-stress Responses in Pentylenetetrazole Models of Epilepsy

European Neurological Review ◽

10.17925/enr.2009.04.01.76 ◽

2009 ◽

Vol 4 (1) ◽

pp. 76 ◽

Cited By ~ 2

Author(s):

Hans-J Bidmon ◽

Erwin-J Speckmann ◽

Karl J Zilles ◽

◽

...

Keyword(s):

Animal Models ◽

Stress Responses ◽

Gene Networks ◽

Molecular Mechanisms ◽

Complex Disease ◽

Ongoing Research ◽

Complex Interactions ◽

Cellular Stress Responses ◽

Clonic Seizures ◽

Oxidative Stress Responses

Ongoing research has elucidated a large variety of genes, proteins and enzyme products that are affected in epilepsy. Despite the pharmacological advances achieved by the development of antiepileptic drugs, numerous patients become pharmacoresistant. Therefore, animal models addressing these complex interactions among compensatory gene-expression cascades and consecutive molecular mechanisms are still a necessity for research-based gene and pharmacotherapy. In this article, we focus on pentylenetetrazole models to study the consequences of tonic–clonic seizures. We address two complex and closely linked aspects: alterations in neurotransmission and oxidative-stress responses. Reviewing just these two aspects highlights the need for a more standardised use of animal models and methods to allow a better integration of data from different lines of research. The latter will be most applicable for the understanding of complex disease-related interactions of gene networks, proteins and enzyme products and timely, research-based development of future therapeutic options.

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Prioritization of biological processes based on the reconstruction and analysis of associative gene networks describing the response of plants to adverse environmental factors

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj21.065 ◽

2021 ◽

Vol 25 (5) ◽

pp. 580-592

Author(s):

P. S. Demenkov ◽

E. A. Oshchepkova ◽

T. V. Ivanisenko ◽

V. A. Ivanisenko

Keyword(s):

Environmental Factors ◽

Ion Transport ◽

Gene Networks ◽

Crop Production ◽

Molecular Genetic ◽

Saline Stress ◽

Cadmium Content ◽

Biological Processes ◽

Genetic Mechanisms ◽

Associative Gene Networks

Methods for prioritizing or ranking candidate genes according to their importance based on specific criteria via the analysis of gene networks are widely used in biomedicine to search for genes associated with diseases and to predict biomarkers, pharmacological targets and other clinically relevant molecules. These methods have also been used in other fields, particularly in crop production. This is largely due to the development of technologies to solve problems in marker-oriented and genomic selection, which requires knowledge of the molecular genetic mechanisms underlying the formation of agriculturally valuable traits. A new direction for the study of molecular genetic mechanisms is the prioritization of biological processes based on the analysis of associative gene networks. Associative gene networks are heterogeneous networks whose vertices can depict both molecular genetic objects (genes, proteins, me tabolites, etc.) and the higher-level factors (biological processes, diseases, external environmental factors, etc.) related to regulatory, physicochemical or associative interactions. Using a previously developed method, biological processes involved in plant responses to increased cadmium content, saline stress and drought conditions were prioritized according to their degree of connection with the gene networks in the SOLANUM TUBEROSUM knowledge base. The prioritization results indicate that fundamental processes, such as gene expression, post-translational modifications, protein degradation, programmed cell death, photosynthesis, signal transmission and stress response play important roles in the common molecular genetic mechanisms for plant response to various adverse factors. On the other hand, a group of processes related to the development of seeds (“seeding development”) was revealed to be drought specific, while processes associated with ion transport (“ion transport”) were included in the list of responses specific to salt stress and processes associated with the metabolism of lipids were found to be involved specifically in the response to cadmium.

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Bioinformatics Methods in Medical Genetics and Genomics

International Journal of Molecular Sciences ◽

10.3390/ijms21176224 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6224

Author(s):

Yuriy L. Orlov ◽

Ancha V. Baranova ◽

Tatiana V. Tatarinova

Keyword(s):

Systems Biology ◽

Protein Interactions ◽

Gene Networks ◽

Drug Targets ◽

Molecular Mechanisms ◽

Medical Genetics ◽

Biomedical Literature ◽

Literature Mining ◽

Proteomics Data ◽

Medical Genomics

Medical genomics relies on next-gen sequencing methods to decipher underlying molecular mechanisms of gene expression. This special issue collects materials originally presented at the “Centenary of Human Population Genetics” Conference-2019, in Moscow. Here we present some recent developments in computational methods tested on actual medical genetics problems dissected through genomics, transcriptomics and proteomics data analysis, gene networks, protein–protein interactions and biomedical literature mining. We have selected materials based on systems biology approaches, database mining. These methods and algorithms were discussed at the Digital Medical Forum-2019, organized by I.M. Sechenov First Moscow State Medical University presenting bioinformatics approaches for the drug targets discovery in cancer, its computational support, and digitalization of medical research, as well as at “Systems Biology and Bioinformatics”-2019 (SBB-2019) Young Scientists School in Novosibirsk, Russia. Selected recent advancements discussed at these events in the medical genomics and genetics areas are based on novel bioinformatics tools.

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Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

Hämostaseologie ◽

10.1055/s-0038-1656647 ◽

1996 ◽

Vol 16 (02) ◽

pp. 114-138 ◽

Cited By ~ 6

Author(s):

R. E. Scharf

Keyword(s):

Genetic Basis ◽

Molecular Mechanisms ◽

Molecular Genetic ◽

Platelet Membrane ◽

Clinical Aspects ◽

Membrane Glycoprotein ◽

Membrane Glycoproteins ◽

Membrane Expression ◽

Receptor Complexes ◽

Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

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Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

Current Bioinformatics ◽

10.2174/1574893614666190204152500 ◽

2019 ◽

Vol 14 (7) ◽

pp. 591-601 ◽

Cited By ~ 1

Author(s):

Aravind K. Konda ◽

Parasappa R. Sabale ◽

Khela R. Soren ◽

Shanmugavadivel P. Subramaniam ◽

Pallavi Singh ◽

...

Keyword(s):

Expression Pattern ◽

Gene Networks ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Wrky Transcription Factor ◽

Functional Enrichment ◽

Differentially Expressed ◽

Callose Deposition ◽

Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

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Adhesion and Growth of Neuralized Mouse Embryonic Stem Cells on Parylene-C/SiO2 Substrates

Materials ◽

10.3390/ma14123174 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3174

Author(s):

Alan F. Murray ◽

Evangelos Delivopoulos

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Protein Interactions ◽

Molecular Mechanisms ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Primary Neurons ◽

Tissue Engineering Scaffolds ◽

Parylene C ◽

Unexpected Outcome

Neuronal patterning on microfabricated architectures has developed rapidly over the past few years, together with the emergence of soft biocompatible materials and tissue engineering scaffolds. Previously, we introduced a patterning technique based on serum and the biopolymer parylene-C, achieving highly compliant growth of primary neurons and astrocytes on different geometries. Here, we expanded this technique and illustrated that neuralized cells derived from mouse embryonic stem cells (mESCs) followed stripes of variable widths with conformity equal to or higher than that of primary neurons and astrocytes. Our results indicate the presence of undifferentiated mESCs, which also conformed to the underlying patterns to a high degree. This is an exciting and unexpected outcome, as molecular mechanisms governing cell and ECM protein interactions are different in stem cells and primary cells. Our study enables further investigations into the development and electrophysiology of differentiating patterned neural stem cells.

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Telomere Shortening and Psychiatric Disorders: A Systematic Review

Cells ◽

10.3390/cells10061423 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1423

Author(s):

Pedro A. Pousa ◽

Raquel M. Souza ◽

Paulo Henrique M. Melo ◽

Bernardo H. M. Correa ◽

Tamires S. C. Mendonça ◽

...

Keyword(s):

Oxidative Stress ◽

Psychological Distress ◽

Mental Disorders ◽

Psychiatric Disorders ◽

Telomere Length ◽

Traumatic Stress ◽

Molecular Mechanisms ◽

Cochrane Library ◽

Telomere Shortening ◽

Anxiety Depression

Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress (“Traumatic Stress Disorder” or “Anxiety Disorder” or “depression”) and telomere length (“cellular senescence”, “oxidative stress” and “telomere”) was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.

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Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression

Cells ◽

10.3390/cells10020389 ◽

2021 ◽

Vol 10 (2) ◽

pp. 389

Author(s):

Marisol Miranda-Galvis ◽

Reid Loveless ◽

Luiz Paulo Kowalski ◽

Yong Teng

Keyword(s):

Head And Neck Cancer ◽

Environmental Factors ◽

Head And Neck ◽

Neck Cancer ◽

Molecular Mechanisms ◽

Metastatic Cancer ◽

Environmental Drivers ◽

Cancer Pathogenesis ◽

Gene Environment ◽

The Impact

Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

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