Standardized microarrays may bring us one step closer

A new study by 64 renowned scientists may bring us one step closer to personalized medical treatment–that is, medical treatment tailored to each person’s unique genetic make-up and medical condition. The study shows researchers how to get more consistent and reliable results when using a technology called microarrays or gene chips. Microarrays allow scientists to see how differences in gene expression are linked to specific diseases. Improving and standardizing microarray experiments will also allow earlier detection of diseases like cancer.

“The microarray is fairly new so, right now, researchers are using a lot of different methods and protocols in microarray experiments. That makes it hard for researchers to compare their results to results from other labs,” said Kenneth Olden, Ph.D., Director of the National Institute of Environmental Health Sciences (NIEHS). “When scientists start using the same methods, equipment and reagents, data can be compared across the entire field of medicine and scientific advances will come more quickly.”

The study, conducted by the Toxicogenomics Research Consortium, which is funded by the National Institute of Environmental Health Sciences, part of the National Institutes of Health, was initiated in 2001 to asses what causes variation in gene expression experiments within and between labs, as well as within and between microarray platforms. The TRC is a consortium of 7 research centers including: NIEHS Microarray Group of the National Center for Toxicogenomics, Duke University, Fred Hutchinson Cancer Research Center/University of Washington, Massachusetts Institute of Technology, Oregon Health and Sciences University, and University of North Carolina at Chapel Hill. Icoria Inc. was also a research partner. The paper appears in the May issue of Nature Methods.

The researchers systematically examined the processes involved in most microarray or gene expression studies, and found that using a standardized process led to more consistent results.

The researchers also found that using commercially manufactured microarrays produced the best results that can be more easily replicated. Using microarrays made in-house by each lab gave less consistent results.

“So far, gene expression data have been very useful in understanding diseases and biological processes,” said Brenda Weis, Ph.D., an author on the study who works at NIEHS. “But if we standardize protocols the knowledge we gain from microarray studies can be used to improve clinical practice. For example, in the Netherlands, microarrays are being used to develop therapies for patients with specific subtypes of breast cancer.”

Microarrays allow scientists to look at very subtle changes in many genes at one time. They provide a snapshot of what genes are expressed or active, in normal and diseased cells. When normal cells or tissues are compared to those known to be diseased, patterns of gene expression can emerge, allowing scientists to classify the severity of the disease and to identify the genes that can be targeted for therapy. This is how microarrays can potentially be used to develop personalized medical treatments.

The study analyzed results from seven separate laboratories using two different mouse RNA samples, including a liver RNA and a five-tissue pooled RNA sample, and 12 microarrays, which were either produced commercially or produced in-house by each lab.

“When we started the Consortium in 2001, we were being responsive to a stated need by researchers who use microarrays to study disease processes. Researchers want standards in order to minimize variation,” said Dr. Weis. “If microarrays are to be used effectively in the clinic to diagnose patients and design patient-tailored therapies, they will need to be like any other clinical tests; they will need to be standardized.”

“No individual lab could do something like this. A study of this magnitude requires a substantial commitment of time, money and expertise, and is well suited to be lead by the federal government,” said Dr. Weis.