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Fast Breaking Comments

By John Quackenbush

ESI Special Topics, June 2006
Citing URL - http://www.esi-topics.com/fbp/2006/june06-JohnQuackenbush.html

John Quackenbush answers a few questions about this month's fast breaking paper in the field of Biology & Biochemistry.


From •>>June 2006 - [late entry]
Field: Biology & Biochemistry
Article Title: Independence and reproducibility across microarray platforms
Authors: Larkin, JE;Frank, BC;Gavras, H;Sultana, R;Quackenbush, J
Journal: NAT METHODS
Volume: 2
Issue: 5
Page: 337-343
Year: MAY 2005
* Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA.
* Inst Genom Res, Rockville, MD 20850 USA.
* Boston Univ, Med Ctr, Boston, MA 02118 USA.
* Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
* George Washington Univ, Dept Biochem, Washington, DC 20037 USA.
* Johns Hopkins Univ, Bloomberg Sch Publ Htlh, Dept Stat, Baltimore, MD 21205 USA.

ST:  Why do you think your paper is highly cited?

Although DNA microarrays have become an almost ubiquitous tool in molecular biology, there have been many reports suggesting that the technology is unreliable. Our experience had always been quite different and we believed that the results from DNA microarrays reflected the underlying biology.


“Our results showed that if one uses microarrays to ask a biological question, that the biology dominates any signal that might come from the particular choice of microarray platform.”

This paper, along with two others that were published concurrently but independently, each used slightly different approaches to address whether results from different microarray platforms are consistent and whether they provide meaningful results.

Our results showed that if one uses microarrays to ask a biological question, that the biology dominates any signal that might come from the particular choice of microarray platform.

For the 10% of genes on the arrays we analyzed where the results were platform-dependent, we also showed that they correlated poorly quantitative reverse transcription PCR (RT-PCR), suggesting problems with these genes in hybridization-based assays.

ST:  Does it describe a new discovery, methodology, or synthesis of knowledge?

I am not sure if it is any one of these. It really was an analysis of a widely used technology and a demonstration of its general reliability.

ST:  Could you summarize the significance of your paper in layman's terms?

DNA is the blueprint that cells use to make proteins—and cells are essentially machines built of proteins. Although every cell in the body contains the same DNA, different cell types have to do different things and so, for example, brain and liver cells make different proteins, as do healthy and diseased cells.

And since cells with the same DNA do different things, that means that the cells have to make different proteins. DNA microarrays are "gene chips" that allow scientists to observe which genes turn on and off in different cell types, and our work showed that if one makes careful measurements, the results are reliable and can be used as a way to begin to develop an understanding of the how and why different cells behave.

ST:  How did you become involved in this research, and were any problems encountered along the way?

It was frustrating to use a technique for years and have other scientists question the validity of the results it provided, often due to anecdotal evidence. We went into this project with open minds, not knowing whether we would see concordance on a gene-by-gene level or if we would have to look more generally at broad classes of gene functions to see similarity across different array types. We were surprised to find that nearly 90% of the genes showed the same expression patterns independent of the type of DNA microarray used.

ST:  Are there any social or political implications for your research?

Not directly. But if one looks at the Human Genome Project, its greatest impact has not been due to having a reference human genome sequence. Rather, the technologies it has spawned are what are most likely to have an impact on how we diagnose, manage, and treat disease.

DNA microarrays are the most widely used genomic technology and out work has been important in convincing scientists that they can, indeed, move forward with microarray-based studies.End

John Quackenbush, Ph.D.
Professor of Computational Biology and Bioinformatics
Department of Biostatistics 
Dana-Farber Cancer Institute
Boston, MA, USA


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ESI Special Topics, June 2006
Citing URL - http://www.esi-topics.com/fbp/2006/june06-JohnQuackenbush.html

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