Analyzing illumina gene expression microarray data from different tissues: methodological aspects of data analysis in the metaxpress consortium.
Analyzing illumina gene expression microarray data from different tissues: methodological aspects of data analysis in the metaxpress consortium.
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DOI：
10.1371/journal.pone.0050938
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ziegler A
中科院分区：
文献类型：
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作者：
Schurmann C;Heim K;Schillert A;Blankenberg S;Carstensen M;Dörr M;Endlich K;Felix SB;Gieger C;Grallert H;Herder C;Hoffmann W;Homuth G;Illig T;Kruppa J;Meitinger T;Müller C;Nauck M;Peters A;Rettig R;Roden M;Strauch K;Völker U;Völzke H;Wahl S;Wallaschofski H;Wild PS;Zeller T;Teumer A;Prokisch H;Ziegler A
基因表达谱芯片在分子生物学和功能基因组学中有着广泛的应用。实验和技术的变化使得不同研究的荟萃分析具有挑战性。在总共3358个样本中，所有样本均来自德国人群队列，我们研究了数据预处理的效果以及全血细胞和血液单核细胞基因表达数据中样本处理的变异性，这些数据在Illumina HumanHT-12 v3 BeadChip阵列上测量。在应用log 2或方差稳定化变换后，基因表达信号强度相似。在所有队列中，第一主成分（PC）解释了总变异的95%以上。技术因素极大地影响了信号强度值，尤其是Illumina芯片分配（33-48%的方差）、RNA扩增批次（12-24%）、RNA分离批次（16%）和样品储存时间，特别是全血细胞样品的献血和RNA分离之间的时间（2-3%），以及单核细胞样品的RNA分离和扩增之间的时间（2%）。在两种样本类型中，白色血细胞组成参数是影响全血细胞样本中表达信号强度的最强生物学因素（3%），其次是性别（1-2%）。已知的单核苷酸多态性（SNPs）位于38%的分析探针序列中，其中4%包括常见的SNPs（次要等位基因频率>5%）。在测试的SNP中，1.4%显著改变了探针特异性表达信号（Bonferroni校正的p值<0.05），但是在几乎一半的这些事件中，尽管发生了错配，信号强度甚至增加。因此，探针内的绝大多数SNP对杂交效率没有显著影响。总之，对一些选定的技术因素的调整大大提高了基因表达分析的可靠性。对于荟萃分析，尤其需要进行这种调整。
Microarray profiling of gene expression is widely applied in molecular biology and functional genomics. Experimental and technical variations make meta-analysis of different studies challenging. In a total of 3358 samples, all from German population-based cohorts, we investigated the effect of data preprocessing and the variability due to sample processing in whole blood cell and blood monocyte gene expression data, measured on the Illumina HumanHT-12 v3 BeadChip array. Gene expression signal intensities were similar after applying the log2 or the variance-stabilizing transformation. In all cohorts, the first principal component (PC) explained more than 95% of the total variation. Technical factors substantially influenced signal intensity values, especially the Illumina chip assignment (33–48% of the variance), the RNA amplification batch (12–24%), the RNA isolation batch (16%), and the sample storage time, in particular the time between blood donation and RNA isolation for the whole blood cell samples (2–3%), and the time between RNA isolation and amplification for the monocyte samples (2%). White blood cell composition parameters were the strongest biological factors influencing the expression signal intensities in the whole blood cell samples (3%), followed by sex (1–2%) in both sample types. Known single nucleotide polymorphisms (SNPs) were located in 38% of the analyzed probe sequences and 4% of them included common SNPs (minor allele frequency >5%). Out of the tested SNPs, 1.4% significantly modified the probe-specific expression signals (Bonferroni corrected p-value<0.05), but in almost half of these events the signal intensities were even increased despite the occurrence of the mismatch. Thus, the vast majority of SNPs within probes had no significant effect on hybridization efficiency. In summary, adjustment for a few selected technical factors greatly improved reliability of gene expression analyses. Such adjustments are particularly required for meta-analyses.
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影响因子：
3.7
作者：
Miller BG;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
影响因子：
5.8
作者：
Chen, Lin S.;Storey, John D.
通讯作者：
Storey, John D.
透明细胞肾细胞癌基因表达的荟萃分析定义了一种变异子组，并鉴定了性别对肿瘤生物学的影响。
影响因子：
23.4
作者：
Brannon, A. Rose;Haake, Scott M.;Hacker, Kathryn E.;Pruthi, Raj S.;Wallen, Eric M.;Nielsen, Matthew E.;Rathmell, W. Kimryn
通讯作者：
Rathmell, W. Kimryn