Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.
Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.
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DOI：
10.1371/journal.pone.0128230
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Moses EK
中科院分区：
文献类型：
--
作者：
Yong HE;Melton PE;Johnson MP;Freed KA;Kalionis B;Murthi P;Brennecke SP;Keogh RJ;Moses EK
子痫前期（PE）是一种严重的高血压妊娠疾病，具有显著的遗传成分。许多遗传研究，包括我们自己的研究，已经从不同的功能群中获得了许多易感基因。此外，对母胎界面组织的转录组分析也同样产生了许多差异表达的基因。通常这两种方法之间几乎没有重叠，尽管在两种方法中发现的基因都与PE显著相关。因此，我们采取了一种新的综合生物信息学方法来分析易感基因和PE转录组共同的途径。使用Illumina Human Ht12v4和Wg6v3 BeadChips，对分娩时收集的n = 65个正常血压和n = 60个PE基底蜕膜组织进行转录组分析。利用R软件包库lumi和limma对转录数据进行预处理，进行通路分析。使用Pathway Studio对路径进行分析和构建。我们检测了10个候选基因，它们来自以下功能群：激活素/抑制素信号- acvr1， ACVR1C, ACVR2A， INHA， INHBB；结构组分- col4a1， COL4A2和M1家族氨基肽- erap1， ERAP2和LNPEP。这些易感基因的主要共同调控/靶点是AGT、IFNG、IL6、INHBA、SERPINE1、TGFB1和VEGFA。在PE个体转录组中，与易感基因相关的前两类通路是细胞凋亡和细胞信号传导（p < 0.001）。因此，来自不同功能群的易感基因通过共同的调节因子/靶点共享相似的下游通路，其中一些在PE中发生改变。本研究有助于更好地了解易感基因如何在PE的发展中相互作用。有了这些知识，就可以对这些关键通路中PE易感基因进行更有针对性的功能分析，以检查它们对PE的发病机制和严重程度的贡献。
Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling—ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components—COL4A1, COL4A2 and M1 family aminopeptidases—ERAP1, ERAP2 and LNPEP. Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis and severity of PE.
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影响因子：
7.3
作者：
Hsu P;Nanan RK
通讯作者：
Nanan RK
影响因子：
2.1
作者：
Chang, Shuenn-Dyh;Chao, An-Shine;Wang, Tzu-Hao
通讯作者：
Wang, Tzu-Hao
影响因子：
5.3
作者：
Guo, GL;Lade, JA;Brennecke, SP
通讯作者：
Brennecke, SP
DOI：
10.1111/j.1552-6909.2006.00115.x
发表时间：
2007-01-01
影响因子：
1.8
作者：
Anderson, Cindy M.
通讯作者：
Anderson, Cindy M.
影响因子：
5.8
作者：
Du, Pan;Kibbe, Warren A.;Lin, Simon M.
通讯作者：
Lin, Simon M.