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Published on: July 23, 2012
Identification and characterization of differentially expressed genes from human microglial cell samples infected
Manoj Kumar Gupta1, Santosh Kumar Behera1, Budheswar Dehury1
1Biomedical Informatics Centre, ICMR-Regional Medical Research Centre, Chandrasekharpur, Odisha, India.
Background & Objectives:
Limited studies have been reported on Japanese encephalitis (JE) with reference to microarray data analysis. The present study involved an in silico approach for identification and characterization of differentially expressed genes in human microglial cell (CHME3) samples, infected with P20778 strain of Japanese encephalitis virus (JEV).
Methods:
Gene expression data (GSE57330) belonging to mRNA expression profile of CHME3 cells infected with JEV, was downloaded from the gene expression omnibus (GEO) database, processed and normalized by robust multichip averaging (RMA) method using affy packages of R. The Bayes method was used to correct multiple testing. The log fold change (logFC > 1) and p< 0.05 were used as cut-off to identify differentially expressed genes (DEGs). The newly identified hub genes were set at the centre for construction of protein-protein interaction network using search tool for the retrieval of interacting genes/proteins (STRING) database considering human genome as reference. Gene ontology and pathway enrichment analysis of the hub gene and its associated genes were performed using STRING and DAVID tool.
Results:
Microarray data analysis revealed that STAT1 gene was down-regulated during JEV infection. STAT1 gene was found to interact with tyrosine protein kinase family members, and showed strong interaction with JAK1 and JAK2 genes.
Interpretation & Conclusion:
The identified transcription factors and the binding sites in the promoter region of STAT1 gene might act as potential drug targets in near future.
Insights
Japanese encephalitis virus (JEV) infection down-regulates STAT1 gene expression in human microglial cells. This finding, derived from microarray analysis, highlights STAT1 as a potential therapeutic target for treating JEV infections.
Area of Science:
- Genomics
- Virology
- Immunology
Background:
- Limited research exists on Japanese encephalitis (JE) using microarray data analysis.
- Japanese encephalitis virus (JEV) poses a significant global health challenge.
Purpose of the Study:
- To identify and characterize differentially expressed genes in human microglial cells (CHME3) infected with JEV using an in silico approach.
- To explore potential therapeutic targets for JEV infection.
Main Methods:
- Downloaded and processed gene expression data (GSE57330) from the GEO database.
- Utilized R packages and the Bayes method for data normalization and multiple testing correction.
- Constructed protein-protein interaction networks and performed gene ontology/pathway enrichment analysis.
Main Results:
- STAT1 gene was identified as down-regulated in CHME3 cells upon JEV infection.
- STAT1 demonstrated interactions with tyrosine protein kinase family members, including JAK1 and JAK2.
- Analysis revealed potential drug targets within the promoter region of the STAT1 gene.
Conclusions:
- The STAT1 gene and its interacting partners represent potential therapeutic targets for JEV infection.
- Transcription factors and binding sites in the STAT1 promoter region may serve as future drug targets.
