scholarly journals Identification of Key Ischemic Stroke Genes by Computational Systems Biology

2021 ◽  
Author(s):  
Rongting Yue ◽  
Abhishek Dutta
Keyword(s):  
Ischemic Stroke ◽  
Experimental Validation ◽  
Causes Of Death ◽  
Expression Patterns ◽  
Computational Systems Biology ◽  
Protein Protein Interaction ◽  
Gene Modules ◽  
High Connectivity ◽  
Computational Systems ◽  
Weighted Correlation

Abstract Stroke is one of the leading causes of death in humans. Even if patients survive from stroke, they may suffer sequelae such as disability. Treatment for strokes remains unsatisfactory due to an incomplete understanding of its mechanisms. This study investigates Ischemic Stroke (IS), a primary subtype of stroke, through analyses based on microarray data. Limma (in R)derives differentially expressed genes, and the protein-protein interaction (PPI) network is mapped from the database. Gene co-expression patterns are obtained for clustering gene modules by the Weighted Correlation Network Analysis (WGCNA), and genes with high connectivity in the significantly co-expressed modules are selected as key regulators. Common hubs are identified as Cdkn1a, Nes and Anxa2. Based on our analyses, we hypothesize that these hubs might play a key role in the onset and progression of IS. Result suggests the potential of identifying unexplored key regulators by the systemic method used in this work. Further analyses aim at expanding candidate genes for screening biomarkers for IS, and experimental validation is required on identified potential hubs.

scholarly journals Identification of Key Ischemic Stroke Genes by Computational Systems Biology

2021 ◽  
Author(s):  
Rongting Yue ◽  
Abhishek Dutta
Keyword(s):  
Ischemic Stroke ◽  
Experimental Validation ◽  
Causes Of Death ◽  
Expression Patterns ◽  
Computational Systems Biology ◽  
Protein Protein Interaction ◽  
Gene Modules ◽  
High Connectivity ◽  
Computational Systems ◽  
Weighted Correlation

Stroke is one of the leading causes of death in humans. Even if patients survive from stroke, they may suffer sequelae such as disability. Treatment for strokes remains unsatisfactory due to an incomplete understanding of its mechanisms. This study investigates Ischemic Stroke (IS), a primary subtype of stroke, through analyses based on microarray data. Limma (in R)derives differentially expressed genes, and the protein-protein interaction (PPI) network is mapped from the database. Gene co-expression patterns are obtained for clustering gene modules by the Weighted Correlation Network Analysis (WGCNA), and genes with high connectivity in the significantly co-expressed modules are selected as key regulators. Common hubs are identified as Cdkn1a, Nes and Anxa2. Based on our analyses, we hypothesize that these hubs might play a key role in the onset and progression of IS. Result suggests the potential of identifying unexplored key regulators by the systemic method used in this work. Further analyses aim at expanding candidate genes for screening biomarkers for IS, and experimental validation is required on identified potential hubs.

C-fos, ERK1/2, MAP2, NOTCH1 Proteins Expression Patterns in Human Cerebral Cortex Neurons after Ischemic Stroke

2020 ◽  
Vol 75 (3) ◽  
pp. 226-233
Author(s):  
Svetlana P. Sergeeva ◽  
Aleksey V. Lyundup ◽  
Valery V. Beregovykh ◽  
Petr F. Litvitskiy ◽  
Aleksey A. Savin ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Ischemic Stroke ◽  
Expression Patterns ◽  
Immunohistochemical Method ◽  
Left Middle Cerebral Artery ◽  
Contralateral Hemisphere ◽  
Human Cerebral Cortex ◽  
Fos Protein ◽  
Urgent Task ◽  
Indirect Immunoperoxidase

Background. The search for protein (these include c-fos, ERK1/2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task. Aims to reveal c-fos, ERK1/2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS. Materials and methods. We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 the zone adjacent to the necrotic tissue focus; 2 zone remote from the previous one by 47 cm; 3 zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1/2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method. Results. Moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1/2 and MAP2 positive neurons compared to the control only in samples of zone 1. Conclusions. With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.

Differential Drug Target Selection in Blood Coagulation: What can we get from Computational Systems Biology Models?

2020 ◽  
Vol 26 (18) ◽  
pp. 2109-2115 ◽  
Author(s):  
Mikhail A. Panteleev ◽  
Anna A. Andreeva ◽  
Alexey I. Lobanov
Keyword(s):  
Blood Coagulation ◽  
Biological Network ◽  
Target Selection ◽  
Anticoagulation Therapy ◽  
Differential Regulation ◽  
Coagulation Cascade ◽  
Computational Systems Biology ◽  
Analysis Strategies ◽  
Optimal Target ◽  
Computational Systems

Discovery and selection of the potential targets are some of the important issues in pharmacology. Even when all the reactions and the proteins in a biological network are known, how does one choose the optimal target? Here, we review and discuss the application of the computational methods to address this problem using the blood coagulation cascade as an example. The problem of correct antithrombotic targeting is critical for this system because, although several anticoagulants are currently available, all of them are associated with bleeding risks. The advantages and the drawbacks of different sensitivity analysis strategies are considered, focusing on the approaches that emphasize: 1) the functional modularity and the multi-tasking nature of this biological network; and 2) the need to normalize hemostasis during the anticoagulation therapy rather than completely suppress it. To illustrate this effect, we show the possibility of the differential regulation of lag time and endogenous thrombin potential in the thrombin generation. These methods allow to identify the elements in the blood coagulation cascade that may serve as the targets for the differential regulation of this system.

scholarly journals Identifying Conserved Generic Aspergillus spp. Co-Expressed Gene Modules Associated with Germination Using Cross-Platform and Cross-Species Transcriptomics

2021 ◽  
Vol 7 (4) ◽  
pp. 270
Author(s):  
Tim J. H. Baltussen ◽  
Jordy P. M. Coolen ◽  
Paul E. Verweij ◽  
Jan Dijksterhuis ◽  
Willem J. G. Melchers
Keyword(s):  
Comparative Analysis ◽  
Expression Patterns ◽  
Biological Processes ◽  
Polarized Growth ◽  
Black Module ◽  
Cross Platform ◽  
Gene Modules ◽  
Opportunistic Human Pathogen ◽  
Dependent Transport ◽  
Blue Module

Aspergillus spp. is an opportunistic human pathogen that may cause a spectrum of pulmonary diseases. In order to establish infection, inhaled conidia must germinate, whereby they break dormancy, start to swell, and initiate a highly polarized growth process. To identify critical biological processes during germination, we performed a cross-platform, cross-species comparative analysis of germinating A. fumigatus and A. niger conidia using transcriptional data from published RNA-Seq and Affymetrix studies. A consensus co-expression network analysis identified four gene modules associated with stages of germination. These modules showed numerous shared biological processes between A. niger and A. fumigatus during conidial germination. Specifically, the turquoise module was enriched with secondary metabolism, the black module was highly enriched with protein synthesis, the darkgreen module was enriched with protein fate, and the blue module was highly enriched with polarized growth. More specifically, enriched functional categories identified in the blue module were vesicle formation, vesicular transport, tubulin dependent transport, actin-dependent transport, exocytosis, and endocytosis. Genes important for these biological processes showed similar expression patterns in A. fumigatus and A. niger, therefore, they could be potential antifungal targets. Through cross-platform, cross-species comparative analysis, we were able to identify biologically meaningful modules shared by A. fumigatus and A. niger, which underscores the potential of this approach.

scholarly journals Molecular Analysis of Prothrombotic Gene Variants in Patients with Acute Ischemic Stroke and with Transient Ischemic Attack

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 723
Author(s):  
Gustavo Cernera ◽  
Marika Comegna ◽  
Monica Gelzo ◽  
Marcella Savoia ◽  
Dario Bruzzese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Causes Of Death ◽  
Southern Italy ◽  
Large Population ◽  
Mthfr C677t ◽  
Geographic Area ◽  
Gene Variants ◽  
Interesting Possibility ◽  
Ischemic Attack

Background and objectives: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. Materials and Methods:we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants. Results: we did not observe significant differences between TIA and the GP for any of the variants, while the allele frequencies of methylene-tetrahydrofolate reductase (MTHFR) C677T, beta-fibrinogen -455G>A and factor (FXIII) V34L were significantly higher in patients with IS than in the subjects from the GP. No significant interaction was observed with sex. Conclusions: the present data argue that some gene variants have a role in IS and this appears to be an interesting possibility to be pursued in large population studies to help design specific strategies for IS prevention.

scholarly journals Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 35
Author(s):  
Sahar Aghakhani ◽  
Naouel Zerrouk ◽  
Anna Niarakis
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Systems Biology ◽  
Healing Process ◽  
Metabolic Reprogramming ◽  
Critical Event ◽  
Wound Healing Process ◽  
Computational Systems Biology ◽  
Structural Framework ◽  
Computational Systems

Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modeling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.

scholarly journals Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
Taesic Lee ◽  
Hyunju Lee
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Expression Patterns ◽  
Protein Protein Interactions ◽  
Hub Genes ◽  
Gene Modules ◽  
Gene Regulatory ◽  
The Brain

Alzheimer’s disease (AD) and diabetes mellitus (DM) are known to have a shared molecular mechanism. We aimed to identify shared blood transcriptomic signatures between AD and DM. Blood expression datasets for each disease were combined and a co-expression network was used to construct modules consisting of genes with similar expression patterns. For each module, a gene regulatory network based on gene expression and protein-protein interactions was established to identify hub genes. We selected one module, where COPS4, PSMA6, GTF2B, GTF2F2, and SSB were identified as dysregulated transcription factors that were common between AD and DM. These five genes were also differentially co-expressed in disease-related tissues, such as the brain in AD and the pancreas in DM. Our study identified gene modules that were dysregulated in both AD and DM blood samples, which may contribute to reveal common pathophysiology between two diseases.

scholarly journals Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunmiao Jiang ◽  
Gongbo Lv ◽  
Jinxin Ge ◽  
Bin He ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Expression Patterns ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
Gata Transcription Factor ◽  
Starting Point ◽  
Evolutionary Features ◽  
First Time

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.

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