Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17p, Hanover, 30559, Germany.
Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Carl-Neuberg-Str. 1, Hanover, 30625, Germany.
BMC Genomics. 2018 Jul 13;19(1):530. doi: 10.1186/s12864-018-4914-4.
Infections 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.
We 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.
A 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.
西尼罗河病毒(WNV)感染会攻击宿主的神经组织,并改变其中的基因表达水平。一些单独的研究已经基于 DNA 微阵列的测量分析了转录组中的这些变化。单个微阵列研究产生了一个高维数据结构,其中研究的基因数量远远超过可用的样本量。因此,这些研究的科学证据水平相当低,结果可能仍然不确定。此外,个别研究集中在不同类型的组织或感染后不同的时间点。因此,很难对 WNV 感染引起的神经组织中的转录变化做出一般性的陈述。我们在公共数据库中筛选了与 WNV 感染相关的转录组表达研究,并使用不同的分析管道对这些数据进行荟萃分析,目的是获得更稳定的结果并提高证据水平。
我们生成了 WNV 感染的神经组织与对照样本之间差异表达基因的新列表。将这些基因与免疫组织荟萃分析的结果进行比较,以找出组织特异性差异。虽然有 5879 个基因仅在神经组织中被识别,15 个基因仅在免疫组织中被识别,44 个基因在两种组织中都被共同检测到。大多数原始研究的发现都可以通过荟萃分析得到证实,而且具有更高的统计功效,但也有一些与 WNV 相关的基因和 GO 术语是新发现的。此外,我们还确定了与某些感染过程相关的基因本体术语,这些术语在差异表达基因中显著富集。在神经组织中,有 17 个基因本体术语存在显著差异,在免疫组织中有 2 个术语。
对我们研究结果的批判性讨论表明荟萃分析方法有其优点和局限性。总之,产生的基因列表、确定的基因本体术语和网络重建似乎比个别研究的结果更可靠。我们的荟萃分析为进一步研究 WNV 感染引起的神经组织中的转录机制提供了基础。