Zhang Ji-Gang, Xu Chao, Zhang Lan, Zhu Wei, Shen Hui, Deng Hong-Wen
a Center of Bioinformatics and Genomics, Department of Global Biostatistics and Data Science , Tulane University , New Orleans , LA , USA.
b Computational Science , The Jackson Laboratory , Bar Harbor , ME , USA.
Transcription. 2019 Jun;10(3):137-146. doi: 10.1080/21541264.2019.1575159. Epub 2019 Feb 5.
Gene transcription is regulated with distinct sets of regulatory factors at multiple levels. Transcriptional and post-transcriptional regulation constitute two major regulation modes of gene expression to either activate or repress the initiation of transcription and thereby control the number of proteins synthesized during translation. Disruptions of the proper regulation patterns at transcriptional and post-transcriptional levels are increasingly recognized as causes of human diseases. Consequently, identifying the differential gene expression at transcriptional and post-transcriptional levels respectively is vital to identify potential disease-associated and/or causal genes and understand their roles in the disease development. Here, we proposed a novel method with a linear mixed model that can identify a set of differentially expressed genes at transcriptional and post-transcriptional levels. The simulation and real data analysis showed our method could provide an accurate way to identify genes subject to aberrant transcriptional and post-transcriptional regulation and reveal the potential causal genes that contributed to the diseases.
基因转录在多个水平上由不同的调控因子组进行调节。转录调控和转录后调控构成了基因表达的两种主要调控模式,它们可以激活或抑制转录起始,从而控制翻译过程中合成的蛋白质数量。转录水平和转录后水平上正常调控模式的破坏越来越被认为是人类疾病的病因。因此,分别在转录水平和转录后水平上鉴定差异基因表达对于识别潜在的疾病相关基因和/或致病基因以及了解它们在疾病发展中的作用至关重要。在此,我们提出了一种基于线性混合模型的新方法,该方法可以在转录水平和转录后水平上识别一组差异表达基因。模拟和实际数据分析表明,我们的方法能够提供一种准确的方式来识别受到异常转录和转录后调控的基因,并揭示导致疾病的潜在致病基因。