Bioinformatics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS Comput Biol. 2011 Jan 6;7(1):e1001049. doi: 10.1371/journal.pcbi.1001049.
We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain "connectome" from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS.
我们研究了成年啮齿动物大脑中基因表达与神经解剖连接之间的全球关系。我们利用了来自大脑架构管理系统的大鼠大脑“连接组”的大型数据集(942 个脑区和超过 5000 个连接),并使用统计方法将数据与来自艾伦大脑图谱的 142 个解剖区域的 17530 个基因的基因表达特征相关联。我们的分析表明,成年基因表达特征与连接具有统计学上的显著关系。特别是,具有相似表达谱的脑区往往具有相似的连接谱,而这种效应并非完全归因于空间相关性。此外,连接的脑区具有更相似的表达模式。通过一种简单的优化方法,我们确定了一组与神经解剖连接最相关的基因,并发现这组基因富含参与神经元发育和轴突导向的基因。许多基因与神经发育障碍有关,如自闭症谱系障碍。我们的研究结果有可能揭示基因表达模式在影响神经元活动和连接中的作用,这对我们理解大脑疾病具有潜在的应用价值。补充数据可在 http://www.chibi.ubc.ca/ABAMS 上获得。