Differential expression analysis of human endogenous retroviruses based on ENCODE RNA-seq data.
Differential expression analysis of human endogenous retroviruses based on ENCODE RNA-seq data.
复制标题
DOI：
10.1186/s12920-015-0146-5
复制
发表时间：
2015-11-03
影响因子：
2.7
通讯作者：
Frishman D
中科院分区：
文献类型：
--
作者：
Haase K;Mösch A;Frishman D
人内源性逆转录病毒（herv）具有长末端重复序列（LTRs），具有启动子活性，因此可以影响邻近基因的表达。HERV与不同类型癌症的关系已经得到了充分的证明。然而，到目前为止，还没有对健康和疾病中多种细胞类型的HERV表达模式进行系统的研究。特别是，全面ENCODE数据集的出版已经促进了许多基因表达研究，但迄今为止还没有一个专门针对herv。我们基于冷泉港实验室和加州理工学院提供的ENCODE Tier 1和Tier 2 RNA-seq数据，对HERV表达进行了全面的差异分析。这项分析是针对12个不同细胞系中的单个HERV位点和整个HERV家族进行的，其中6个对应于正常情况，另外6个代表癌细胞类型。虽然主成分分析显示两组细胞表现出可区分的表达模式，但我们无法将这些差异与一个或多个特定的HERV家族联系起来。两个样品的表达模式与另一个生产实验室的相应细胞系不相似。相反，它们表现出癌症形成的迹象和多能性标记HERVH的表达，尽管它们分别被归类为正常细胞系和分化细胞。我们的研究表明，ENCODE数据在不同的贡献实验室之间通常具有可比性，并且HERV元件的分析可以为细胞的分化和疾病状态提供新的见解，而这些在关注蛋白质编码基因时很容易被忽视。我们的发现提示了HERV在癌变过程中的表达变化。本文的在线版本（doi:10.1186/s12920-015-0146-5）包含补充材料，可供授权用户使用。
Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which possess promoter activity and can therefore influence the expression of neighboring genes. HERV involvement in different types of cancer has already been thoroughly documented. However, so far there has been no systematic study of HERV expression patterns in a multitude of cell types in health and disease. In particular, the publication of the comprehensive ENCODE dataset has already facilitated many gene expression studies, but none so far focusing exclusively on HERVs. We present a comprehensive differential analysis of HERV expression based on ENCODE Tier 1 and Tier 2 RNA-seq data produced by Cold Spring Harbor Laboratories and the California Institute of Technology. This analysis was conducted for individual HERV loci and for entire HERV families in twelve different cell lines, of which six correspond to the normal condition and the other six represent cancer cell types. Although the principal component analysis revealed that the two groups of cells show distinguishable expression patterns, we were not able to link these differences to one or multiple particular HERV families. Two samples exhibit expression patterns, which are not similar to the corresponding cell lines of the other producing lab. Instead they show signs of cancer formation and expression of the pluripotency marker HERVH, despite being classified as a normal cell line and a differentiated cell, respectively. Our study demonstrates that ENCODE data are generally comparable between the different contributing labs and that the analysis of HERV elements can provide novel insights into differentiation and disease state of a cell that are easily overlooked when focusing on protein-coding genes. Our findings hint at a change in HERV expression during cancerogenesis. The online version of this article (doi:10.1186/s12920-015-0146-5) contains supplementary material, which is available to authorized users.