title: Human transcriptome array for high-throughput clinical studies.
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.
authors.affiliation: Stanford Genome Technology Center and Department of Biochemistry, Stanford University, Palo Alto, CA 94304, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xu
authors.forename: Junhee
authors.initials: J
authors.lastname: Seok
authors.forename: Michael N
authors.initials: MN
authors.lastname: Mindrinos
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Schweitzer
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Julie
authors.initials: J
authors.lastname: Wilhelmy
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Clark
authors.forename: Karen
authors.initials: K
authors.lastname: Kapur
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.forename: John D
authors.initials: JD
authors.lastname: Storey
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Maier
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Wing Hung
authors.initials: WH
authors.lastname: Wong
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Xiao
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009928:Organ Specificity / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
chemical_list: D022661:RNA, Untranslated