Human transcriptome array for high-throughput clinical studies

Weihong Xu, Junhee Seok, Michael N. Mindrinos, Anthony C. Schweitzer, Hui Jiang, Julie Wilhelmy, Tyson A. Clark, Karen Kapur, Yi Xing, Malek Faham, John D. Storey, Lyle L. Moldawer, Ronald V. Maier, Ronald G. Tompkins, Wing Hung Wong, Ronald W. Davis, Wenzhong Xiao

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3707-3712
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number9
DOIs
StatePublished - Mar 1 2011

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Blood leukocyte
  • Exon junction
  • Gene isoform
  • Next-generation sequencing

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    Xu, W., Seok, J., Mindrinos, M. N., Schweitzer, A. C., Jiang, H., Wilhelmy, J., Clark, T. A., Kapur, K., Xing, Y., Faham, M., Storey, J. D., Moldawer, L. L., Maier, R. V., Tompkins, R. G., Wong, W. H., Davis, R. W., & Xiao, W. (2011). Human transcriptome array for high-throughput clinical studies. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3707-3712. https://doi.org/10.1073/pnas.1019753108