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Life Science Technologies<br />
Genomics<br />
860<br />
Featured Participants<br />
Affym<strong>et</strong>rix<br />
www.affym<strong>et</strong>rix.com<br />
Agilent<br />
www.agilent.com<br />
Ambry Gen<strong>et</strong>ics<br />
www.ambrygen.com<br />
Expression An<strong>al</strong>ysis<br />
www.expressionan<strong>al</strong>ysis.<br />
com<br />
Illumina<br />
www.illumina.com<br />
Life Technologies<br />
www.lif<strong>et</strong>echnologies.com<br />
Oxford Gene Technology<br />
www.ogt.co.uk<br />
Pathwork Diagnostics<br />
www.pathworkdx.com<br />
PerkinElmer<br />
www.perkinelmer.com<br />
Washington University<br />
School of Medicine in St.<br />
Louis<br />
medschool.wustl.edu<br />
tools, the concept of what makes a microarray has begun to evolve.<br />
Tradition<strong>al</strong>ly, microarrays consisted only of nucleotides attached to<br />
a solid surface, but variations on this theme <strong>al</strong>so exist. For example,<br />
Life Technologies (Carlsbad, C<strong>al</strong>ifornia) developed its TaqMan<br />
OpenArray Re<strong>al</strong>-Time PCR plates, which include 3,072 wells.<br />
ìThe arrays can be formatted from our inventory of eight million<br />
TaqMan assays,î says Jami Elliott, mark<strong>et</strong> development manager<br />
at Life Technologies. The re<strong>al</strong>-time PCR assays, which use TaqMan<br />
probes (so named because these assays rely on the Taq polymerase),<br />
can be used to measure gene expression, identify biomarkers,<br />
and more.<br />
If eight million choices arenít enough, Joshua Trotta, director, business<br />
development gen<strong>et</strong>ic an<strong>al</strong>ysis at Life Technologies, says, ìWe can<br />
custom design one.î<br />
Ongoing Data Dilemmas<br />
Rather than making microarrays, Expression An<strong>al</strong>ysis, a Quintiles<br />
company in Durham, North Carolina, uses arrays to conduct a wide<br />
range of studies for customers, such as gene-expression profiling. In<br />
doing so, Expression An<strong>al</strong>ysis uses microarrays from sever<strong>al</strong> vendors,<br />
including Affym<strong>et</strong>rix, Illumina, and Fluidigm in South San Francisco,<br />
C<strong>al</strong>ifornia. According to Pat Hurban, vice president of R&D at<br />
Expression An<strong>al</strong>ysis, ìMicroarrays are very mature as a technology,<br />
but there are still a number of ch<strong>al</strong>lenges in working with the data,<br />
especi<strong>al</strong>ly when you want to drill down into the biology.î He adds,<br />
ìItís one thing to provide a statistic<strong>al</strong> treatment of data, but another to<br />
understand the pathways involved and translate that into biology.î This<br />
company uses a collection of propri<strong>et</strong>ary tools in an effort to bridge that<br />
knowledge gap.<br />
In fact, Hurban advises researchers to reassess the best technology to<br />
use as a project advances. ìYou must be mindful of the technic<strong>al</strong> limitations<br />
of microarrays,î he says. For example, he points out that microarrays<br />
provide excellent discovery tools. ìItís not uncommon to identify<br />
specific genes of interest with microarrays,î Hurban says. ìWhen<br />
it comes to translation<strong>al</strong> research, the question becomes: Is it advisable<br />
www.sciencemag.org/products<br />
to continue on a microarray platform as you g<strong>et</strong> closer to the clinic or<br />
transition to a more suitable and robust technology, such as [quantitative]<br />
PCR or sequencing.î<br />
In a recent project, Expression An<strong>al</strong>ysis worked with a client who had<br />
what Hurban describes as ìa preliminary gene-signature panel that was<br />
very useful as a diagnostic in a certain indication area.î Researchers at<br />
Expression An<strong>al</strong>ysis worked with patient samples from the sponsor to<br />
put that signature on microarrays. ìWe showed the v<strong>al</strong>idity of this panel,î<br />
Hurban says. ìUltimately, the sponsor wanted to turn this signature<br />
into a diagnostic and became concerned with the microarray results<br />
because the precision was a bit of a ch<strong>al</strong>lenge.î Consequently, the client<br />
eventu<strong>al</strong>ly turned to a PCR-based platform for the fin<strong>al</strong> diagnostic. As<br />
a result, Hurban says, ìYou might use a microarray to some point, and<br />
then go to another technology.î<br />
Tomorrowís Tools<br />
The ongoing advances in sequencing technology have made more than a<br />
few experts predict the demise of microarrays. For example, Elizab<strong>et</strong>h<br />
Chao, director of translation<strong>al</strong> medicine at Ambry Gen<strong>et</strong>ics in Aliso<br />
Viejo, C<strong>al</strong>ifornia, says, ìThe expression arrays that Iíve been using for<br />
14 years are incredible tools, but RNA sequencing is starting to replace<br />
microarrays in research and translation.î She adds, ìSequencing<br />
is not replacing microarrays in the clinic<strong>al</strong> s<strong>et</strong>ting y<strong>et</strong>, but it probably<br />
will soon.î<br />
The data generated by sequencing can be both benefici<strong>al</strong> and ch<strong>al</strong>lenging.<br />
Sequencing provides a gigantic amount of data in a short period of<br />
time, but it can be difficult to interpr<strong>et</strong> so much data. Chao is confident<br />
that interpr<strong>et</strong>ing sequencing data will improve rapidly. She says, ìBioinformatics<br />
has re<strong>al</strong>ly come up, and new m<strong>et</strong>hods are making it possible<br />
to look at sequences across the entire genome.î<br />
To evolve with changes in technology, some companies provide services<br />
that teach researchers to use the growing amounts of data. For<br />
example, Todd Smith, senior leader, research and application at PerkinElmer,<br />
says, ìWe can help people as they go from microarrays to<br />
DNA sequencing.î This can include an<strong>al</strong>ytic<strong>al</strong> techniques for handling<br />
the higher volume of data. These technologies, though, will likely<br />
complement each other, according to Smith and his colleagues. ìThere<br />
are applications where microarrays work best, and others where sequencing<br />
works best,î says Williams. ìThere are areas where sequencing<br />
wonít work well, but microarrays can.î As an example, Williams says<br />
they are about to start a study that involves 160 samples that must be<br />
processed in a matter of weeks. ìThereís no way we could go through<br />
that with sequencing and g<strong>et</strong> it turned around in time to have meaningful<br />
data,î he says. Moreover, Smith says microarrays are superior<br />
to sequencing when it comes to searching for structur<strong>al</strong> variations in<br />
a genome.<br />
Though some experts may have differing opinions, the gener<strong>al</strong> consensus<br />
predicts that microarrays will continue to benefit basic research<br />
and provide clinic<strong>al</strong> tools related to genomics. In the end, microarrays<br />
will advance where they work the best.<br />
Mike May is a publishing consultant for science and technology.<br />
DOI: 10.1126/science.opms.p1300072<br />
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