brain-coX: investigating and visualising gene co-expression in seven human brain transcriptomic datasets.
brain-coX: investigating and visualising gene co-expression in seven human brain transcriptomic datasets.
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DOI：
10.1186/s13073-017-0444-y
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发表时间：
2017-06-08
期刊：
影响因子：
12.3
通讯作者：
Bahlo M
中科院分区：
文献类型：
--
作者：
Freytag S;Burgess R;Oliver KL;Bahlo M
神经和精神健康疾病的发病机制通常涉及多基因、复杂的相互作用以及特定于大脑和发育的生物机制。这些特征使识别此类疾病的疾病基因具有挑战性，因为传统的优先排序工具并不是专门为处理人脑的复杂性而定制的。因此，我们开发了一个新的网络应用程序-大脑-COX-它基于死后人类大脑中的七个基因表达数据集提供基因优先排序和伴随的可视化，这是迄今为止收集到的最大的此类资源。我们测试了我们的工具是否可以正确地对37条大脑特定的KEGG通路和17种精神疾病的已知基因进行优先排序。我们获得了接近50%的平均灵敏度，同时达到了大约75%的特异度。我们还将Brain-Cox的表现与其主要竞争对手Endeavour和Toppgene的表现进行了比较，重点是发现新关联的能力。使用SFARI自闭症基因收集的一个子集，我们表明Brain-Cox的优先顺序与SFARI自己的精心挑选的基因分类最相似。Brain-COX是第一个针对人脑的优先排序和可视化网络工具，可以通过http://shiny.bioinf.wehi.edu.au/freytag.s/.免费访问本文的在线版本(doi：10.1186/s13073-0170444-y)包含补充材料，授权用户可以使用。
The pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms. These characteristics make identification of disease genes for such disorders challenging, as conventional prioritisation tools are not specifically tailored to deal with the complexity of the human brain. Thus, we developed a novel web-application—brain-coX—that offers gene prioritisation with accompanying visualisations based on seven gene expression datasets in the post-mortem human brain, the largest such resource ever assembled. We tested whether our tool can correctly prioritise known genes from 37 brain-specific KEGG pathways and 17 psychiatric conditions. We achieved average sensitivity of nearly 50%, at the same time reaching a specificity of approximately 75%. We also compared brain-coX’s performance to that of its main competitors, Endeavour and ToppGene, focusing on the ability to discover novel associations. Using a subset of the curated SFARI autism gene collection we show that brain-coX’s prioritisations are most similar to SFARI’s own curated gene classifications. brain-coX is the first prioritisation and visualisation web-tool targeted to the human brain and can be freely accessed via http://shiny.bioinf.wehi.edu.au/freytag.s/. The online version of this article (doi:10.1186/s13073-017-0444-y) contains supplementary material, which is available to authorized users.