In silico investigation and comparative functional enrichment analysis of the human-respiratory syncytial virus (RSV) and the human-metapneumovirus (MPV) gene interaction networks

Author(s):  
Erasmia Rouka ◽  
Chrissi Hatzoglou ◽  
Konstantinos Gourgoulianis ◽  
Sotirios Zarogiannis
Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 997
Author(s):  
Deborah A. Sival ◽  
Martinica Garofalo ◽  
Rick Brandsma ◽  
Tom A. Bokkers ◽  
Marloes van den Berg ◽  
...  

In degenerative adult onset ataxia (AOA), dystonic comorbidity is attributed to one disease continuum. However, in early adult onset ataxia (EOA), the prevalence and pathogenesis of dystonic comorbidity (EOAD+), are still unclear. In 80 EOA-patients, we determined the EOAD+-prevalence in association with MRI-abnormalities. Subsequently, we explored underlying biological pathways by genetic network and functional enrichment analysis. We checked pathway-outcomes in specific EOAD+-genotypes by comparing results with non-specifically (in-silico-determined) shared genes in up-to-date EOA, AOA and dystonia gene panels (that could concurrently cause ataxia and dystonia). In the majority (65%) of EOA-patients, mild EOAD+-features concurred with extra-cerebellar MRI abnormalities (at pons and/or basal-ganglia and/or thalamus (p = 0.001)). Genetic network and functional enrichment analysis in EOAD+-genotypes indicated an association with organelle- and cellular-component organization (important for energy production and signal transduction). In non-specifically, in-silico-determined shared EOA, AOA and dystonia genes, pathways were enriched for Krebs-cycle and fatty acid/lipid-metabolic processes. In frequently occurring EOAD+-phenotypes, clinical, anatomical and biological pathway analyses reveal shared pathophysiology between ataxia and dystonia, associated with cellular energy metabolism and network signal transduction. Insight in the underlying pathophysiology of heterogeneous EOAD+-phenotype-genotype relationships supports the rationale for testing with complete, up-to-date movement disorder gene lists, instead of single EOA gene-panels.


Author(s):  
Mohit Jha ◽  
Anvita Gupta ◽  
Sudha Singh ◽  
Khushhali Menaria Pandey

Co-infection with tuberculosis (TB) is the preeminent cause of demise in human immunodeficiency virus (HIV) infected individuals. However, diagnosis of TB, particularly in the presence of an HIV co-infection, can be limiting owing to the high inaccuracy associated with conventional diagnostic strategies. Here we determine dysregulated pathways in TB-HIV co-infection and HIV infection utilizing coexpression networks. Primarily, we utilized preservation statistics to identify gene modules that exhibit a weak conservation of network topology within HIV infected and TB-HIV co-infected networks. Raw data was downloaded from Gene Expression Omnibus (GSE50834) and duly pre-processed. Co-expression networks for each condition (HIV infected and TB-HIV co-infected) were constructed independently. Preservation of HIV infected network edges was evaluated with respect to TB-HIV co-infected and vice versa using weighted correlation network analysis. Two out of the 22 modules were identified as exhibiting weak preservation in both conditions. Functional enrichment analysis identified that weakly preserved modules were pertinent to the condition under study. For instance, weakly preserved TBHIV co-infected module T1 enriched for genes associated with mitochondrion exhibited the highest fraction of gene interaction pairs exclusive to TB-HIV co-infection. Concisely, we illustrated the application of using preservation statistics to detect modules functionally linked with dysregulated pathways in disease, as exemplified by the mitochondrion module T1. Our analyses discovered gene clusters that are non-randomly linked with the disease. Highly specific gene pairs pointed to interactions between known markers of disease and favoured identification of possible markers that are likely to be associated with the disease.


2020 ◽  
Vol 21 (5) ◽  
pp. 1831 ◽  
Author(s):  
Ruth Barral-Arca ◽  
Alberto Gómez-Carballa ◽  
Miriam Cebey-López ◽  
Xabier Bello ◽  
Federico Martinón-Torres ◽  
...  

Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.


2021 ◽  
Vol 36 ◽  
pp. 153331752110217
Author(s):  
Liu Lu ◽  
Wen-Zhuo Dai ◽  
Xi-Chen Zhu ◽  
Tao Ma

This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.


2021 ◽  
Vol 19 ◽  
pp. 205873922110328
Author(s):  
Xinxin Xu ◽  
Qingqing Ma ◽  
Mu Lin ◽  
Mubo Liu ◽  
Chaolin Huang ◽  
...  

Introduction Mutations in the filaggrin ( FLG) gene are known to cause ichthyosis vulgaris. Methods We used whole-genome sequencing (WGS) technology to investigate the genetic causes of rare and complex inherited diseases including rheumatoid arthritis, ichthyosis, and congenital fibrosis of the extraocular muscles type 1 (CFEOM1) in a Chinese family. WGS was performed in four topics, and the identified candidate mutations were further verified through Sanger sequencing. Results We identified a mutation in FLG gene (g.152280098 C>A, p.E2422∗) that may be associated with ichthyosis and arthritis. Moreover, a mutation in KIF21A (g.39726207 G>A, p.R954 W) was also determined in affected members as the cause of CFEOM1. The gene interaction network demonstrated an interesting correlation between FLG and genes associated with arthritis and ichthyosis. Functional enrichment analysis of these interacting genes revealed several possible pathways that might be linked to arthritis and ichthyosis. Conclusion In general, we confirmed a loss of function mutation in the FLG gene associated with ichthyosis vulgaris and rheumatoid arthritis in this family.


2021 ◽  
Author(s):  
Jyoti Shekhawat ◽  
Ashita Gadwal ◽  
Manoj Khokhar ◽  
Kavya Gauba ◽  
Shruti Gupta ◽  
...  

Abstract HPV contributes to the pathogenesis of H&NC. H&NC patients are diagnosed at an advanced stage and are more disposed to lymph node metastasis. There is conflicting evidence with regard to distant metastasis in H&NC. Identification of potential candidate genes which can be used as predictors of prognosis in HPV positive/negative H&NCs are needed. We initiated the study using publicly available microarray gene expression datasets from the GEO. Functional enrichment analysis of significant genes was done using the DAVID. The PPI network was constructed in the STRING and visualized using Cytoscape. The CytoHubb plugin was utilized to identify the key genes in this complicated network. The MCODE plugin was applied to screen out significant gene modules. Hub genes identified were analysed for overall survival (OS) in GEPIA. Analysis of the miRNA and transcription factors targeting the hub gene with significance was done using miRNet. GEO datasets GSE39366, GSE40774, GSE117973 were used in this study. We identified 67 overlapping DEGs which were significant. Gene Ontology identified key terms as ‘cellular component’, ‘biological process’, and ‘molecular function’ respectively. Cytoscape and MCODE revealed two significant modules. The common hub genes identified using cytohubb plugin. CAV1 has been reported to be significantly associated with OS in H&NC patients. 3 targeting miRNA and 54 transcription factors were identified using miRNet. In-silico survival and expression analyses revealed CAV1 as a candidate gene that may be used to predict the course of disease progression in HPV positive and HPV negative H&NC patients. Further invitro studies validating CAV1 and its three target miRNAs as predictors of prognosis in H&NC are highly warranted.


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