Consensus comparative analysis of human embryonic stem cell-derived cardiomyocytes.

Consensus comparative analysis of human embryonic stem cell-derived cardiomyocytes.
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人胚胎干细胞来源的心肌细胞的共识比较分析

DOI:
10.1371/journal.pone.0125442
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Wong HS
Wong HS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang S;Poon E;Xie D;Boheler KR;Li RA;Wong HS

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全球的转录分析已经进行了人类胚胎干细胞(hESC)衍生的心肌细胞(CM),以确定分子和途径的重要人类CM分化,但在文化和分析条件的变化,导致不同的研究之间的结果大相径庭。共识调查,以确定基因和基因集丰富的多项研究是重要的,揭示差异基因表达固有的人CM分化独立于上述变量,但缺乏可靠的方法进行这种比较。我们从多个微阵列研究中检测了hESC和hESC-CM之间的差异基因表达。对于单基因分析,我们在7个数据集中鉴定了hESC-CM中表达水平增加的基因,这些基因以前没有被强调过。对于基因集分析,我们开发了一种新的算法,共识比较分析(CSSCMP),能够评估丰富的基因集从异质性数据源。基于理论分析和实验验证,CSSCMP是更有效的,更不容易受到实验的变化比传统的方法。我们将CSSCMP应用于hESC-CM微阵列数据,并揭示了新的基因集富集(例如,糖皮质激素刺激),并确定了可能介导这种反应的基因。我们的研究结果提供了重要的分子信息内在的hESC-CM分化。数据和Matlab代码可以从S1 Data下载。
Global transcriptional analyses have been performed with human embryonic stem cells (hESC) derived cardiomyocytes (CMs) to identify molecules and pathways important for human CM differentiation, but variations in culture and profiling conditions have led to greatly divergent results among different studies. Consensus investigation to identify genes and gene sets enriched in multiple studies is important for revealing differential gene expression intrinsic to human CM differentiation independent of the above variables, but reliable methods of conducting such comparison are lacking. We examined differential gene expression between hESC and hESC-CMs from multiple microarray studies. For single gene analysis, we identified genes that were expressed at increased levels in hESC-CMs in seven datasets and which have not been previously highlighted. For gene set analysis, we developed a new algorithm, consensus comparative analysis (CSSCMP), capable of evaluating enrichment of gene sets from heterogeneous data sources. Based on both theoretical analysis and experimental validation, CSSCMP is more efficient and less susceptible to experimental variations than traditional methods. We applied CSSCMP to hESC-CM microarray data and revealed novel gene set enrichment (e.g., glucocorticoid stimulus), and also identified genes that might mediate this response. Our results provide important molecular information intrinsic to hESC-CM differentiation. Data and Matlab codes can be downloaded from S1 Data.
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