Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, Biochemistry and Developmental Biology, 00014 University of Helsinki, Finland.
Nucleic Acids Res. 2011 Oct;39(18):e123. doi: 10.1093/nar/gkr513. Epub 2011 Jul 10.
Alternative splicing of pre-mRNA generates protein diversity. Dysfunction of splicing machinery and expression of specific transcripts has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantification of expression levels of the majority of exons and facilitates the discovery of alternative splicing events. Analysis of exon array data is more challenging than the analysis of gene expression data and there is a need for reliable quantification of exons and alternatively spliced variants. We introduce a novel, computationally efficient methodology, Multiple Exon Array Preprocessing (MEAP), for exon array data pre-processing, analysis and visualization. We compared MEAP with existing pre-processing methods, and validation of six exons and two alternatively spliced variants with qPCR corroborated MEAP expression estimates. Analysis of exon array data from head and neck squamous cell carcinoma (HNSCC) cell lines revealed several transcripts associated with 11q13 amplification, which is related with decreased survival and metastasis in HNSCC patients. Our results demonstrate that MEAP produces reliable expression values at exon, alternatively spliced variant and gene levels, which allows generating novel experimentally testable predictions.
前体 mRNA 的可变剪接产生蛋白质多样性。剪接机制的功能障碍和特定转录本的表达与癌症的进展和药物反应有关。外显子微阵列技术可实现大多数外显子表达水平的全基因组定量，并有助于发现可变剪接事件。外显子阵列数据分析比基因表达数据分析更具挑战性，并且需要对外显子和可变剪接变体进行可靠的定量。我们引入了一种新颖的、计算效率高的方法，即多外显子阵列预处理（MEAP），用于外显子阵列数据的预处理、分析和可视化。我们将 MEAP 与现有的预处理方法进行了比较，并通过 qPCR 对六个外显子和两个可变剪接变体进行了验证，证实了 MEAP 的表达估计。对头颈部鳞状细胞癌（HNSCC）细胞系的外显子阵列数据分析揭示了与 11q13 扩增相关的几个转录本，这与 HNSCC 患者的生存率降低和转移有关。我们的结果表明，MEAP 可在外显子、可变剪接变体和基因水平上产生可靠的表达值，从而可以产生新的可通过实验验证的预测。
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