基于多视图双聚类方法分析不同哺乳动物早期胚胎发育基因激活差异

Identification of Gene Activation Differences of Early Embryonic Development among Different Mammals Based on MVBC Method

大量分子生物学研究证实,哺乳动物早期胚胎发育具有严格的分子调控机制.但是,不同种类之间早期胚胎发育可能存在的调节差异和分子机理并不清楚.利用比较转录组学方法识别不同物种之间的保守共表达基因簇,对于深入揭示胚胎发育和器官分化十分关键.多视图双聚类方法(Multi-view bi-clustering,MVBC)可以解决胚胎样本中的基因表达信号弱和噪声数据较多的问题,较传统两步法可以更好地找到保守的共表达基因簇.我们使用多视图双聚类这一新方法,在人、鼠和牛胚胎中共鉴定出114个共表达基因模块,并对其中包含数目较多、可信度高的29个基因簇进行了KEGG通路富集分析.结果表明,这些基因簇在三个物种早期胚胎发育中共享的通路大多是核小体与RNA转运等起着基础作用的通路,表明在三个物种间合子特异性转录和翻译机制的建立都相对保守.另外,还发现了在物种内具有相似表达模式的8组基因簇、同一功能通路可在多个基因簇富集,以及信号通路在整个胚胎早期发育过程中呈时序性表达的特点.本研究揭示了三个物种间早期胚胎基因表达模式与通路功能的关系,丰富了物种间早期胚胎发育过程的差异化知识,对进一步研究哺乳动物早期胚胎发育机制有一定帮助.

Lots of molecular biology studies have confirmed that mammalian early embryonic development has strict molecular regulation mechanisms.However,the potential differences and molecular mechanisms of early embryonic development between different mammals remain unclear.The use of comparative transcriptomics to identify conserved co-expressed gene clusters between different species is critical for revealing embryonic development and organ differentiation.A newly proposed multi-view bi-clustering(MVBC)approach can solve the problems of weak gene expression signal and noise data in embryo samples,which could be used to better find conserved co-expressed gene clusters than the traditional two-step method.In this study,we used the MVBC method to identify 114 co-expressing gene modules in human,mouse and bovine embryos,and the KEGG pathway enrichment analysis was carried out on 29 gene clusters with a large number and high credibility.Pathway enrichment analysis showed that the pathways shared by these gene clusters in the early development of three species embryos were mostly nucleosomes,RNA transport and other basic pathways,indicating the establishment of zygote-specific transcription and translation mechanisms among the three species was relatively conservative.We also found eight clusters of genes with similar expression patterns among the species,the same functional pathways in the enrichment of multiple gene clusters,and the temporal expression of signaling pathways in human,mouse,and bovine embryos throughout the early developmental process.The results revealed the relationship between gene expression patterns and pathway functions of early embryos among three species,complementing the knowledge of early embryonic development between species,and provided references for mechanism research of mammalian early embryonic development.