Standardized Microarray Systems

The Toxicogenomics Research Consortium: University of North Carolina at Chapel Hill, Fred Hutchinson Cancer Research Center/University of Washington, Oregon Health and Sciences University, Duke University, Massachusetts Institute of Technology, National Center for Toxicogenomics Microarray Group; and Icoria Inc.
U19ES11391, U19ES11399, U19ES11375, U19ES11384, and U19ES11387

Background: The first papers describing the technique of DNA microarrays appeared in the scientific literature in the mid-1990’s. Since that time, over 15,000 papers have been published in the peer-reviewed literature. Despite the growing popularity of the technique, the reproducibility of results between laboratories and across microarray platforms has been an understudied concern. Differences in techniques, platforms, instrumentation, analytical software, etc. raise questions about the accuracy and reproducibility of results and possibly delay the full benefit of the technique; that of personalizing medical care based on individual genetic susceptibility and response to environmental agents.

Advance: The Toxicogenomics Research Consortium, a group of seven research centers, began a study in 2001 to determine the sources of variability in gene expression profiling results collected across multiple labs using multiple technology platforms and techniques. The study was conducted in seven laboratories, in which two standardized samples were analyzed using twelve microarray platforms. Either laboratory or commercial microarrays were used in each laboratory. Data reproducibility was generally good with within a single platform used in any one laboratory, but was poor between labs. When standardized protocols were used across all labs, reproducibility between the labs improved. The study found that commercially manufactured microarrays produced the most reproducible results.

Implications: The results from these studies indicate that microarray experiments can be comparable across multiple laboratories, especially when a common platform and set of procedures are used. These advances in microarray technology demonstrate to the scientific community how to obtain more consistent and reliable results. Standardizing microarray techniques can accelerate the pace of scientific discovery about biological responses to environmental stressors. Ultimately this could improve our ability to detect very early indicators of diseases like cancer to identify people at risk for environmentally related diseases.

Citation: Members of the Toxicogenomics Research Consortium. Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods. 2005 May;2(5):351-6.