Nature Biotechnology
- 24, 1162 - 1169 (2006)
Published online: 8 September 2006; | doi:10.1038/nbt1238
Rat toxicogenomic study reveals analytical consistency across microarray platformsLei Guo1, Edward K Lobenhofer2, Charles Wang3, Richard Shippy4, Stephen C Harris1, Lu Zhang5, Nan Mei1, Tao Chen1, Damir Herman6, Federico M Goodsaid7, Patrick Hurban2, Kenneth L Phillips2, Jun Xu3, Xutao Deng3, Yongming Andrew Sun8, Weida Tong1, Yvonne P Dragan1 & Leming Shi11
National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA. 2
Cogenics, A Division of Clinical Data, 100 Perimeter Park Drive, Suite C, Morrisville, North Carolina 27560, USA. 3
UCLA David Geffen School of Medicine, Transcriptional Genomics Core, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA. 4
GE Healthcare, 7700 S. River Parkway, Suite #2603, Tempe, Arizona 85284, USA. 5
Solexa, 25861 Industrial Boulevard, Hayward, California 94545, USA. 6
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, Maryland 20894, USA. 7
Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA. 8
Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California 94404, USA.
Correspondence should be addressed to Lei Guo lei.guo@fda.hhs.gov or Leming Shi leming.shi@fda.hhs.gov To validate and extend the findings of the MicroArray Quality Control (MAQC) project, a biologically relevant toxicogenomics data set was generated using 36 RNA samples from rats treated with three chemicals (aristolochic acid, riddelliine and comfrey) and each sample was hybridized to four microarray platforms. The MAQC project assessed concordance in intersite and cross-platform comparisons and the impact of gene selection methods on the reproducibility of profiling data in terms of differentially expressed genes using distinct reference RNA samples. The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons. Further, gene lists generated by fold-change ranking were more reproducible than those obtained by t-test P value or Significance Analysis of Microarrays. Finally, gene lists generated by fold-change ranking with a nonstringent P-value cutoff showed increased consistency in Gene Ontology terms and pathways, and hence the biological impact of chemical exposure could be reliably deduced from all platforms analyzed.
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