Computational identification and validation of alternative splicing in ZSF1 rat RNA-seq data, a preclinical model for type 2 diabetic nephropathy.
Computational identification and validation of alternative splicing in ZSF1 rat RNA-seq data, a preclinical model for type 2 diabetic nephropathy.
复制标题
DOI：
10.1038/s41598-018-26035-x
复制
发表时间：
2018-05-16
影响因子：
4.6
通讯作者：
Zhao S
中科院分区：
文献类型：
--
作者：
Zhang C;Dower K;Zhang B;Martinez RV;Lin LL;Zhao S
肥胖的ZSF1大鼠表现出自发性的时间依赖性糖尿病肾病，被认为是进行性人类糖尿病肾病的高度相关的动物模型。我们之前在12周至41周的六个时间点上确定了疾病动物和对照动物之间的基因表达变化。在这项研究中，在异构体和外显子水平上分析了相同的数据，以揭示可能由选择性剪接控制的其他疾病机制。我们的分析确定了可能与疾病发病机制有关的基因（如Shc1、serinc1、epb4.1 15和Il-33）的其他剪接模式，这在标准基因水平分析中可能被忽视。选择性剪接的基因在细胞粘附、细胞间相互作用/连接和细胞骨架信号通路中富集，而差异表达的基因在免疫应答、G蛋白偶联受体和cAMP信号通路中富集。我们的研究结果表明，从外显子和同工异构体水平的数据分析中可以获得比标准基因水平分析更多的机制见解。考虑到选择性剪接在啮齿动物和人类之间的保守性很差，值得注意的是，这项工作不是翻译的，但这一点是正确的，可以从RNA-seq数据的选择性剪接分析中获得额外的见解。
Obese ZSF1 rats exhibit spontaneous time-dependent diabetic nephropathy and are considered to be a highly relevant animal model of progressive human diabetic kidney disease. We previously identified gene expression changes between disease and control animals across six time points from 12 to 41 weeks. In this study, the same data were analysed at the isoform and exon levels to reveal additional disease mechanisms that may be governed by alternative splicing. Our analyses identified alternative splicing patterns in genes that may be implicated in disease pathogenesis (such as Shc1, Serpinc1, Epb4.1l5, and Il-33), which would have been overlooked in standard gene-level analysis. The alternatively spliced genes were enriched in pathways related to cell adhesion, cell–cell interactions/junctions, and cytoskeleton signalling, whereas the differentially expressed genes were enriched in pathways related to immune response, G protein-coupled receptor, and cAMP signalling. Our findings indicate that additional mechanistic insights can be gained from exon- and isoform-level data analyses over standard gene-level analysis. Considering alternative splicing is poorly conserved between rodents and humans, it is noted that this work is not translational, but the point holds true that additional insights can be gained from alternative splicing analysis of RNA-seq data.
登录
查看更多内容
影响因子：
2.6
作者：
Chanan-Khan, Asher;Miller, Kena C.;Czuczman, Myron S.
通讯作者：
Czuczman, Myron S.
影响因子：
14.9
作者：
Hansen KD;Brenner SE;Dudoit S
通讯作者：
Dudoit S
DOI：
10.1083/jcb.200712086
发表时间：
2008-09-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hirano M;Hashimoto S;Yonemura S;Sabe H;Aizawa S
通讯作者：
Aizawa S
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P