RNA-Seq versus oligonucleotide array assessment of dose-dependent TCDD-elicited hepatic gene expression in miceReportar como inadecuado

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BMC Genomics

, 16:373

First Online: 10 May 2015Received: 06 November 2014Accepted: 27 February 2015DOI: 10.1186-s12864-015-1527-z

Cite this article as: Nault, R., Fader, K.A. & Zacharewski, T. BMC Genomics 2015 16: 373. doi:10.1186-s12864-015-1527-z


BackgroundDose-dependent differential gene expression provides critical information required for regulatory decision-making. The lower costs associated with RNA-Seq have made it the preferred technology for transcriptomic analysis. However, concordance between RNA-Seq and microarray analyses in dose response studies has not been adequately vetted.

ResultsWe compared the hepatic transcriptome of C57BL-6 mice following gavage with sesame oil vehicle, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 μg-kg TCDD every 4 days for 28 days using Illumina HiSeq RNA-Sequencing RNA-Seq and Agilent 4×44 K microarrays using the same normalization and analysis approach. RNA-Seq and microarray analysis identified a total of 18,063 and 16,403 genes, respectively, that were expressed in the liver. RNA-Seq analysis for differentially expressed genes DEGs varied dramatically depending on the P1t cut-off while microarray results varied more based on the fold change criteria, although responses strongly correlated. Verification by WaferGen SmartChip QRTPCR revealed that RNA-Seq had a false discovery rate of 24% compared to 54% for microarray analysis. Dose–response modeling of RNA-Seq and microarray data demonstrated similar point of departure POD and ED50 estimates for common DEGs.

ConclusionsThere was a strong correspondence between RNA-Seq and Agilent array transcriptome profiling when using the same samples and analysis strategy. However, RNA-Seq provided superior quantitative data, identifying more genes and DEGs, as well as qualitative information regarding identity and annotation for dose response modeling in support of regulatory decision-making.

KeywordsRNA-Seq Microarray Comparison TCDD Dose–response Mouse Liver Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1527-z contains supplementary material, which is available to authorized users.

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Autor: Rance Nault - Kelly A Fader - Tim Zacharewski

Fuente: https://link.springer.com/

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