GAITHERSBURG, Md.—With the recent launch of the multidisciplinary Metrology for Gene Expression Program, the National Institute of Standards and Technology (NIST) is hoping to explore and address the challenges associated with the measurement, validation, and quality control of this rapidly expanding field. Over five years and at a cost of $6.25 million, NIST will seek to improve the quality, reliability and comparability of gene expression measurements with microarrays.
Although gene expression studies impact everything from basic biological research to drug discovery and clinical diagnostics, the technologies used to perform these analyses—microarrays being the most prevalent—can be prone to large uncertainties and unexplained measurement variabilities.
"There are numerous scientific and technical questions regarding the reliability, validity, uncertainty, comparability, dynamic range, selectivity/specificity, and linearity of microarray results," explains Dr. Marc Salit, a research chemist in the Analytical Chemistry Division of NIST. For example, one NIST study using three different microarray systems to measure the same sample found that all three systems agreed on only four out of 275 genes identified when examined under the most stringent criteria.
"Our emerging program will study these metrological properties through studying the molecular biology, chemistry, physics, and informatics of the entire measurement process," he adds. For example, to understand microarray gene expression analysis, Salit's group will examine key elements of the technical process, from RNA extraction, sample preparation, and labeling to hybridization, detection, and data analysis.
The NIST program will work with instrument developers and end users to evaluate sources of error and variability in measurement, a method for exploring technical challenges that has worked well in the past for NIST. For example, the External RNA Control Consortium, a group of almost 50 organizations from industry (including array-specialists Affymetrix), academic labs, federal agencies, and other key stakeholders, looked at technical issues arising from RNA quantitation efforts.
The researchers will then use their findings to develop reference data, reference materials, and measurement methods to enable quality assurance for the chemistry, detection methods, and information processing used in microarray analysis. Given that quantitative gene expression data is vital for the pharmacogenomic paradigm to succeed and that companies are now beginning to receive FDA approval for array-based diagnostic kits, global assurance standards will go a long way toward increasing faith in these methods in the scientific and regulatory communities.
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