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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.
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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.
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“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.”
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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.
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.
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.
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.
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.
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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