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Dawn of the gene expression array

Nature Biotechnology volume 24, pages 301–302 (2006)Cite this article

That blind test led to the first gene expression array and the most highly cited paper in Nature Biotechnology1. Lockhart and his colleagues had designed over a hundred thousand oligonucleotides as gene detectors and synthesized them directly onto a high-density array using massively parallel combinatorial chemistry. The tool could quantify mRNA molecules' abundance in cells over three orders of magnitude and unambiguously detect RNAs with frequencies as low as one in 300,000 or about one copy per mammalian cell.

But making the chip wasn't the most important part. After all, Stephen Fodor, founder of Affymetrix, and colleagues had already developed the technique to build oligonucleotides on a solid matrix. Lockhart and his colleagues had to figure out how to prepare the sample, pick what oligos to put on the chip, separate signal from noise and analyze results. Key to this was deliberately including oligos with single-nucleotide mismatches to eliminate confounding signals from cross hybridization.

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References

  1. Lockhart, D.J. et al. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat. Biotechnol. 14, 1675–1680 (1996).

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  2. Schutze, K. & Lahr, G. Identification of expressed genes by laser-mediated manipulation of single cells. Nat. Biotechnol. 16, 737–742 (1998).

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  3. Wodicka, L., Dong, H., Mittmann, M., Ho, M.H. & Lockhart, D.J. Genome-wide expression monitoring in Saccharomyces cerevisiae. Nat. Biotechnol. 15, 1359–1367 (1997).

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Dawn of the gene expression array. Nat Biotechnol 24, 301–302 (2006). https://doi.org/10.1038/nbt0306-301b

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