Shotgun Microarrays: High-throughput Validation of Gene Expression Changes Using Multiple Platforms

Roderick V. Jensen
Wesleyan University and Brigham and Women's Hospital/ Harvard Medical School

DNA Microarrays have emerged as important new tools for the large-scale measurement of differential gene expression in a wide variety of biomedical experiments, comparing normal and diseased tissues, different states of biological processes, and the response to drugs or toxins. A single cDNA or oligonucleotide microarray can provide detailed quantitative information on the levels of expression of thousands of genes. However, as with any laboratory measurement, this data is subject to errors. To identify real changes in gene expression it is essential to understand and model the sources of errors in these measurements. Our laboratory has performed extensive studies of microarray data from multiple microarray platforms including homemade cDNA arrays, Amersham/Motorola CodeLink arrays, Agilent in situ microarrays, and the popular Affymetrix GeneChips. The comparison of differential gene expression measurements both within and across platforms provides the basis for statistical error models essential for the useful interpretation of the data. Our "shotgun microarray" approach has successfully identified gene expression signatures in a variety of different applications ranging from the distinction of normal human tissues, to the classification of cancer, to the identification of genomic differences in young and old tissue samples.