Abstract
BackgroundInfections with the West Nile virus (WNV) can attack neurological tissues in the host and alter gene expression levels therein. Several individual studies have analyzed these changes in the transcriptome based on measurements with DNA microarrays. Individual microarray studies produce a high-dimensional data structure with the number of studied genes exceeding the available sample size by far. Therefore, the level of scientific evidence of these studies is rather low and results can remain uncertain. Furthermore, the individual studies concentrate on different types of tissues or different time points after infection. A general statement regarding the transcriptional changes through WNV infection in neurological tissues is therefore hard to make. We screened public databases for transcriptome expression studies related to WNV infections and used different analysis pipelines to perform meta-analyses of these data with the goal of obtaining more stable results and increasing the level of evidence.ResultsWe generated new lists of genes differentially expressed between WNV infected neurological tissues and control samples. A comparison with these genes to findings of a meta-analysis of immunological tissues is performed to figure out tissue-specific differences. While 5.879 genes were identified exclusively in the neurological tissues, 15 genes were found exclusively in the immunological tissues, and 44 genes were commonly detected in both tissues. Most findings of the original studies could be confirmed by the meta-analysis with a higher statistical power, but some genes and GO terms related to WNV were newly detected, too. In addition, we identified gene ontology terms related to certain infection processes, which are significantly enriched among the differentially expressed genes. In the neurological tissues, 17 gene ontology terms were found significantly different, and 2 terms in the immunological tissues.ConclusionsA critical discussion of our findings shows benefits but also limitations of the meta-analytic approach. In summary, the produced gene lists, identified gene ontology terms and network reconstructions appear to be more reliable than the results from the individual studies. Our meta-analysis provides a basis for further research on the transcriptional mechanisms by WNV infections in neurological tissues.
Highlights
Infections with the West Nile virus (WNV) can attack neurological tissues in the host and alter gene expression levels therein
The produced gene lists, identified gene ontology terms and network reconstructions appear to be more reliable than the results from the individual studies
Our meta-analysis provides a basis for further research on the transcriptional mechanisms by WNV infections in neurological tissues
Summary
Infections with the West Nile virus (WNV) can attack neurological tissues in the host and alter gene expression levels therein. We screened public databases for transcriptome expression studies related to WNV infections and used different analysis pipelines to perform meta-analyses of these data with the goal of obtaining more stable results and increasing the level of evidence. West Nile virus [(WNV); family Flaviviridae, genus Flavivirus] is one of the most important emerging virus infections in Europe. In nature West Nile virus is maintained in an enzootic cycle involving ornithophilic mosquitoes and birds but can infect humans, equines and other vertebrates as illustrated by repeated cases of WNV encephalitis in horses and humans [7, 9,10,11]. WNV spreads to the reticuloendothelial system (RES; e.g kidney, spleen)
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