Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease.
Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease.
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DOI：
10.1007/s10048-017-0509-5
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发表时间：
2017-04
期刊：
影响因子：
2.2
通讯作者：
Summers KM
中科院分区：
文献类型：
--
作者：
Carpanini SM;Wishart TM;Gillingwater TH;Manson JC;Summers KM
发达国家神经退行性疾病的发病率在上个世纪有所上升，同时人类平均寿命也在增加。因此，一个主要的挑战是确定控制神经元健康和活力的基因，以期在衰老过程中增强神经元健康，减少神经退行性疾病的负担。基因表达数据的分析最近已被用来推断基因功能的范围内的组织从共表达网络。我们现在已经将这种方法应用于公共领域中可用的哺乳动物神经系统的转录组数据集。我们已经确定了影响不同神经细胞类型和大脑区域神经元健康和疾病的关键基因。使用人类疾病和敲除小鼠表型、途径和基因本体论术语注释来验证每个共表达簇中基因的功能贡献。此外，许多注释不佳的基因与神经系统功能有关。利用公共领域中的基因表达数据，我们可以验证关键的神经系统基因，重要的是，可以识别具有最小功能注释但具有相同表达模式的其他基因。因此，这些基因是在神经系统健康和疾病中发挥作用的新候选基因，现在可以进一步研究以确认它们在衰老和神经退行性疾病期间的功能和调节。本文的在线版本（doi：10.1007/s10048-017-0509-5）包含补充材料，可供授权用户使用。
The incidence of neurodegenerative diseases in the developed world has risen over the last century, concomitant with an increase in average human lifespan. A major challenge is therefore to identify genes that control neuronal health and viability with a view to enhancing neuronal health during ageing and reducing the burden of neurodegeneration. Analysis of gene expression data has recently been used to infer gene functions for a range of tissues from co-expression networks. We have now applied this approach to transcriptomic datasets from the mammalian nervous system available in the public domain. We have defined the genes critical for influencing neuronal health and disease in different neurological cell types and brain regions. The functional contribution of genes in each co-expression cluster was validated using human disease and knockout mouse phenotypes, pathways and gene ontology term annotation. Additionally a number of poorly annotated genes were implicated by this approach in nervous system function. Exploiting gene expression data available in the public domain allowed us to validate key nervous system genes and, importantly, to identify additional genes with minimal functional annotation but with the same expression pattern. These genes are thus novel candidates for a role in neurological health and disease and could now be further investigated to confirm their function and regulation during ageing and neurodegeneration. The online version of this article (doi:10.1007/s10048-017-0509-5) contains supplementary material, which is available to authorized users.
DOI：
10.1080/15257770.2014.880477
发表时间：
2014
期刊：
Nucleosides, nucleotides & nucleic acids
影响因子：
--
作者：
Dauphinot L;Mockel L;Cahu J;Jinnah HA;Ledroit M;Potier MC;Ceballos-Picot I
通讯作者：
Ceballos-Picot I