Pairwise interactions in gene expression determine a hierarchical transcriptional profile in the human brain

基因表达中的成对相互作用决定了人脑的层级化转录模式

The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data from more than 2000 sites in six human brains,we found that pairwise interactions between genes,without considering any higher-order interactions,are sufficient to predict the transcriptional pattern of the genome for individual brain regions and the transcriptional profile of the entire brain consisting of more than 200 areas.These findings suggest a quadratic complexity of transcriptional patterns in the human brain,which is much simpler than expected.In addition,using a pairwise interaction model,we revealed that the strength of gene-gene interactions in the human brain gives rise to the nearly maximal number of transcriptional clusters,which may account for the functional and structural richness of the brain.

人类大脑是一个高度复杂的系统,其结构和功能受到成千上万个基因的精细调控.这些基因的表达之间存在着错综复杂的相互作用,但是目前对于支配基因间相互作用的基本结构尚不清楚.本研究通过分析Allen研究所提供的6个人脑中2000多个位点的基因转录组数据,发现只需要考虑基因表达之间的成对(二阶)相互作用,而无需考虑任何更高阶的相互作用(HOI),就可以准确地预测单个脑区的基因组转录模式和200多个脑区所构成的脑网络的整体转录模式.这些结果表明,人脑的基因转录模式是由二阶相互作用所主导,这极大地降低了基因表达网络的复杂度.在此基础上,使用二阶相互作用模型进一步揭示了基因表达与脑网络整体性质之间可能存在的深刻关系.本研究发现转录组数据中的基因相互作用强度可以导致脑区聚类数目接近最大,提示进化过程可能通过选择这一基因相互作用强度以实现丰富而复杂的脑功能和结构组织.