Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data

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ID: 291260
2005
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Abstract
Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease. The most popular platform for genome-wide expression profiling is the Affymetrix GeneChip. However, its selection of probes relied on earlier genome and transcriptome annotation which is significantly different from current knowledge. The resultant informatics problems have a profound impact on analysis and interpretation the data. Here, we address these critical issues and offer a solution. We identified several classes of problems at the individual probe level in the existing annotation, under the assumption that current genome and transcriptome databases are more accurate than those used for GeneChip design. We then reorganized probes on more than a dozen popular GeneChips into gene-, transcript- and exon-specific probe sets in light of up-to-date genome, cDNA/EST clustering and single nucleotide polymorphism information. Comparing analysis results between the original and the redefined probe sets reveals ∼30–50% discrepancy in the genes previously identified as differentially expressed, regardless of analysis method. Our results demonstrate that the original Affymetrix probe set definitions are inaccurate, and many conclusions derived from past GeneChip analyses may be significantly flawed. It will be beneficial to re-analyze existing GeneChip data with updated probe set definitions.
Reference Key
openalex_W2135827569 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Manhong Dai, Pinglang Wang, Andrew D. Boyd, Georgi Kostov, Brian D. Athey, Edward G. Jones, William E. Bunney, R Myers, Terence P. Speed, Huda Akil, Stanley J. Watson, Fandong Meng
Journal Nucleic Acids Research
Year 2005
DOI
10.1093/nar/gni179
URL
https://academic.oup.com/nar/article-pdf/33/20/e175/3779716/gni179.pdf
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