Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas.
Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas.
复制标题
DOI：
10.1016/j.placenta.2013.04.007
复制
发表时间：
2013-07
期刊：
影响因子：
3.8
通讯作者：
Piedrahita, J. A.
中科院分区：
文献类型：
--
作者：
Guo, L.;Tsai, S. Q.;Hardison, N. E.;James, A. H.;Motsinger-Reif, A. A.;Thames, B.;Stone, E. A.;Deng, C.;Piedrahita, J. A.
本研究的重点是实施调制模块聚类（MMC），一种新的聚类算法，用于识别先兆子痫和宫内生长受限（IUGR）的分子特征，并识别受影响的microRNA。使用Illumina Human-6 Beadarrays分析了来自正常（40），生长受限（27）和先兆子痫（19）足月妊娠的86个人类胎盘。MMC用于基于胎盘转录组中的相似性生成模块。使用基因集富集分析（GSEA）来预测受影响的microRNA。在71个人类足月胎盘中研究了这些候选microRNA的表达水平，如下：对照（29）; IUGR（26）;和先兆子痫（16）。MMC确定了两个模块，一个代表IUGR胎盘，一个代表先兆子痫胎盘。在代表IUGR的模块中鉴定出326个差异表达基因，在代表先兆子痫的模块中鉴定出889个差异表达基因。与IUGR相关的分子特征的功能分析鉴定出P13 K/AKT、mTOR、p70 S6 K、细胞凋亡和IGF-1信号传导受到影响。GSEA预测microRNA的方差分析表明，miR-194在先兆子痫（p=0.0001）和IUGR（p=0.0304）中均显著下调，miR-149在先兆子痫中显著下调（p=0.0168）。MMC的实施，允许鉴定IUGR和先兆子痫中失调的基因。MMC的可靠性通过与先前的先兆子痫胎盘的线性模型分析进行比较来验证。MMC允许阐明与先兆子痫和IUGR样本子集相关的分子特征。这允许识别这些疾病中受影响的基因，途径和microRNA。
This study focuses on the implementation of modulated modularity clustering (MMC) a new cluster algorithm for the identification of molecular signatures of preeclampsia and intrauterine growth restriction (IUGR), and the identification of affected microRNAs Eighty-six human placentas from normal (40), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays. MMC was utilized to generate modules based on similarities in placental transcriptome. Gene Set Enrichment Analysis (GSEA) was used to predict affected microRNAs. Expression levels of these candidate microRNAs were investigated in seventy-one human term placentas as follows: control (29); IUGR (26); and preeclampsia (16). MMC identified two modules, one representing IUGR placentas and one representing preeclamptic placentas. 326 differentially expressed genes in the module representing IUGR and 889 differentially expressed genes in a module representing preeclampsia were identified. Functional analysis of molecular signatures associated with IUGR identified P13K/AKT, mTOR, p70S6K, apoptosis and IGF-1 signaling as being affected. Analysis of variance of GSEA-predicted microRNAs indicated that miR-194 was significantly down-regulated both in preeclampsia (p=0.0001) and IUGR (p=0.0304), and miR-149 was significantly down-regulated in preeclampsia (p=0.0168). Implementation of MMC, allowed identification of genes disregulated in IUGR and preeclampsia. The reliability of MMC was validated by comparing to previous linear modeling analysis of preeclamptic placentas. MMC allowed the elucidation of a molecular signature associated with preeclampsia and a subset of IUGR samples. This allowed the identification of genes, pathways, and microRNAs affected in these diseases.
登录
查看更多内容
影响因子：
3.7
作者：
Le XF;Almeida MI;Mao W;Spizzo R;Rossi S;Nicoloso MS;Zhang S;Wu Y;Calin GA;Bast RC Jr
通讯作者：
Bast RC Jr
DOI：
10.1161/hypertensionaha.111.176602
发表时间：
2011-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Mishra N;Nugent WH;Mahavadi S;Walsh SW
通讯作者：
Walsh SW
影响因子：
5.3
作者：
Anthony, D. F.;Sin, Y. Y.;Baillie, G. S.
通讯作者：
Baillie, G. S.
DOI：
10.1126/science.1191880
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Onodera T;Sakai T;Hsu JC;Matsumoto K;Chiorini JA;Yamada KM
通讯作者：
Yamada KM
影响因子：
9.3
作者：
Chim, Stephen S. C.;Shing, Tristan K. F.;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis