Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data.

Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data.
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DOI:
10.1093/nar/gni179
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发表时间:
2005-11-10
影响因子:
14.9
通讯作者:
Meng F
Meng F
中科院分区:
生物学2区
文献类型:
--
作者:
Dai M;Wang P;Boyd AD;Kostov G;Athey B;Jones EG;Bunney WE;Myers RM;Speed TP;Akil H;Watson SJ;Meng F

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全基因组表达谱分析是一个强大的工具,涉及新的基因组在健康和疾病的细胞机制。最流行的全基因组表达谱分析平台是Affyssin基因芯片。然而,其探针的选择依赖于早期的基因组和转录组注释,这与当前的知识有显着不同。由此产生的信息学问题对数据的分析和解释产生了深远的影响。在这里,我们将解决这些关键问题并提供解决方案。我们确定了几类问题,在现有的注释中的单个探针水平,假设目前的基因组和转录组数据库比用于基因芯片设计更准确。然后,我们重组探针在十几个流行的基因芯片到基因,转录本和外显子特异性探针集,根据最新的基因组,cDNA/EST聚类和单核苷酸多态性信息。将原始探针组和重新定义的探针组之间的分析结果进行比较,发现先前鉴定为差异表达的基因中存在约30-50%的差异,而与分析方法无关。我们的研究结果表明,原来的Affychip探针集的定义是不准确的,从过去的基因芯片分析得出的许多结论可能是显着的缺陷。使用更新的探针组定义重新分析现有的基因芯片数据将是有益的。
Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease. The most popular platform for genome-wide expression profiling is the Affymetrix GeneChip. However, its selection of probes relied on earlier genome and transcriptome annotation which is significantly different from current knowledge. The resultant informatics problems have a profound impact on analysis and interpretation the data. Here, we address these critical issues and offer a solution. We identified several classes of problems at the individual probe level in the existing annotation, under the assumption that current genome and transcriptome databases are more accurate than those used for GeneChip design. We then reorganized probes on more than a dozen popular GeneChips into gene-, transcript- and exon-specific probe sets in light of up-to-date genome, cDNA/EST clustering and single nucleotide polymorphism information. Comparing analysis results between the original and the redefined probe sets reveals ∼30–50% discrepancy in the genes previously identified as differentially expressed, regardless of analysis method. Our results demonstrate that the original Affymetrix probe set definitions are inaccurate, and many conclusions derived from past GeneChip analyses may be significantly flawed. It will be beneficial to re-analyze existing GeneChip data with updated probe set definitions.
DOI: 10.1073/pnas.1534744100
发表时间: 2003-09-30
影响因子: 11.1
作者:
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通讯作者: Webster, TA
DOI: 10.1093/nar/gkh073
发表时间: 2004-01-01
影响因子: 14.9
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期刊: Genome biology
影响因子: 12.3
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DOI: 10.1073/pnas.011404098
发表时间: 2001-01-02
影响因子: 11.1
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DOI: 10.1093/bioinformatics/btg455
发表时间: 2004-03-01
期刊: BIOINFORMATICS
影响因子: 5.8
作者:
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