Human transcriptome array for high-throughput clinical studies
Human transcriptome array for high-throughput clinical studies
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DOI：
10.1073/pnas.1019753108
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发表时间：
2011-03-01
影响因子：
11.1
通讯作者：
Xiao, Wenzhong
中科院分区：
文献类型：
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作者：
Xu, Weihong;Seok, Junhee;Xiao, Wenzhong
一种690万个特征的人类转录组寡核苷酸阵列[Glue Grant人类转录组(GG-H阵列)]已经被开发出来，用于临床研究中的高通量和成本效益分析。该阵列允许全面检查基因表达和全基因组范围的选择性剪接鉴定，以及检测编码SNPs和非编码转录本。检测了该阵列的性能，并与肝脏和肌肉样本的多个独立重复的mRNA测序(RNA-Seq)结果进行了比较。与每次重复4600万个唯一可映射读数的RNA-Seq相比，GG-H阵列在估计基因和外显子丰度方面具有高度的重复性。虽然两个平台在基因水平上检测到相似的表达变化，但GG-H阵列在外显子水平上更敏感。需要更深的测序才能充分覆盖低丰度转录本。该阵列已在多中心临床计划中实施，并产生了高质量、可重复的数据。考虑到成本、样本可获得性和吞吐量的临床试验要求，GG-H阵列具有广泛的应用。大规模临床基因组研究的一种新方法是首先使用RNA-Seq到足够深度，以发现与疾病过程相关的转录组元件，然后使用定制设计的阵列在数千个患者样本上高通量和可靠地筛选这些元件。
A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing as well as detection of coding SNPs and noncoding transcripts. The performance of the array was examined and compared with mRNA sequencing (RNA-Seq) results over multiple independent replicates of liver and muscle samples. Compared with RNA-Seq of 46 million uniquely mappable reads per replicate, the GG-H array is highly reproducible in estimating gene and exon abundance. Although both platforms detect similar expression changes at the gene level, the GG-H array is more sensitive at the exon level. Deeper sequencing is required to adequately cover low-abundance transcripts. The array has been implemented in a multicenter clinical program and has generated high-quality, reproducible data. Considering the clinical trial requirements of cost, sample availability, and throughput, the GG-H array has a wide range of applications. An emerging approach for large-scale clinical genomic studies is to first use RNA-Seq to the sufficient depth for the discovery of transcriptome elements relevant to the disease process followed by high-throughput and reliable screening of these elements on thousands of patient samples using custom-designed arrays.