**The MAQC Project: Establishing QC Metrics and Thresholds for
Microarray Quality Control**

Leming Shi, FDA/NCTR

Federico M. Goodsaid, FDA/CDER

Uwe Scherf, FDA/CDRH

Raj K. Puri, FDA/CBER

Janet A. Warrington, Affymetrix

Jim Collins, Agilent

Robert A. Setterquist, Ambion

Lu Zhang, Applied Biosystems

Laurence Lamarcq, Clontech

Mark Elliot, Combimatrix

Christophe Van Huffel, Eppendorf

Richard Shippy, GE Healthcare

Yuling Luo, Genospectra

Shawn C. Baker, Illumina

Gavin M. Fischer, Stratagene

David J. Dix, EPA/NHEERL

Marc Salit, NIST

Zoltan Szallasi, Harvard

Roderick V. Jensen, UMass Boston

Weida Tong, FDA/NCTR

(1 page, \<=20 authors)

Microarrays represent a core technology in pharmacogenomics and
toxicogenomics; however, before this technology can successfully and
reliably be applied in clinical practice and regulatory decision-making,
standards and quality measures need to be developed. The Microarray
Quality Control (MAQC) project involves multiple FDA Centers, major
providers of microarray platforms and RNA samples, EPA, NIST, academic
laboratories, and other stakeholders. The MAQC project aims to establish
QC metrics and thresholds for objectively assessing the performance
achievable by various microarray platforms and for assessing the merits
of various data analysis methods for microarray datasets generated from
different platforms. Two RNA samples will be selected for each of the
three species (*i.e*., human, rat, and mouse), and differential gene
expression levels between the two samples will be calibrated with
microarrays and other technologies (*e.g*., QRT-PCR). The resulting
microarray datasets will be used for assessing the precision and
cross-platform/laboratory comparability of the microarray technology,
and the QRT-PCR datasets will enable evaluation of the nature and
magnitude of any systematic biases that may exist between microarray and
QRT-PCR technologies.

Two pilot studies (*i.e*., RNA Sample Selection Pilot and Tissue Mixture
Titration Pilot) have been completed with about 400 hybridizations. As a
result, two commercial RNA samples (*i.e*., the brain RNA sample from
Ambion and the Universal Human Reference RNA (UHRR) from Stratagene) and
two mixtures (25:75 and 75:25, brain:UHRR) have been selected for the
human MAQC main study, which is expected to be completed by September
2005. Each of the microarray platforms from seven vendors (Affymetrix,
Agilent, Applied Biosystems, Combimatrix, Eppendorf, GE Healthcare, and
Illumina) will be evaluated using the same set of four samples in five
technical replicates by at least three test sites per platform,
resulting in more than 420 hybridizations. QRT-PCR assays (Applied
Biosystems) for more than 1,000 genes and QuantiGene assays
(Genospectra) for more than 200 genes will be conducted using the same
set of samples. The MAQC benchmark datasets, which are being accumulated
in the FDA's ArrayTrack system, will be made available to the public in
early 2006. Guidelines for microarray quality control and data analysis
will be developed.

The availability of the calibrated RNA samples combined with the
resulting reference datasets from the MAQC project will allow individual
laboratories to more easily identify and correct procedural failures.
The MAQC project will help improve the microarray technology and foster
its proper applications in the discovery, development and review of
FDA-regulated products. More information about the MAQC project can be
found at <http://edkb.fda.gov/MAQC/>. We apologize for being unable to
list the names of all MAQC participants due to the limitation of space.
Views expressed in this abstract do not necessarily represent those of
the authors' employers.