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Human transcriptome array for high-throughput clinical studies.

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.

Pubmed ID: 21317363

Authors

  • Xu W
  • Seok J
  • Mindrinos MN
  • Schweitzer AC
  • Jiang H
  • Wilhelmy J
  • Clark TA
  • Kapur K
  • Xing Y
  • Faham M
  • Storey JD
  • Moldawer LL
  • Maier RV
  • Tompkins RG
  • Wong WH
  • Davis RW
  • Xiao W
  • Inflammation and Host Response to Injury Large-Scale Collaborative Research Program

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 1, 2011

Associated Grants

  • Agency: NHGRI NIH HHS, Id: P01HG000205
  • Agency: NHGRI NIH HHS, Id: R01HG004634
  • Agency: NIGMS NIH HHS, Id: U54 GM062119
  • Agency: NIGMS NIH HHS, Id: U54GM062119
  • Agency: NCRR NIH HHS, Id: UL1 RR025014

Mesh Terms

  • Alternative Splicing
  • Exons
  • Gene Expression Profiling
  • High-Throughput Screening Assays
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • RNA, Untranslated
  • Reproducibility of Results
  • Sequence Analysis, RNA