Human Genome Solutions
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Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
In 2006, the MicroArray Quality Control (MAQC) consortium published the most comprehensive study to date, assessing the performance and cross platform comparability of microarray data (MAQC Consortium. 2006. Nat. Biotechnol. 24:1151-1161). This study laid a foundation and framework for assessment of microarray performance, highlighting the importance of maintaining a balance between factors such as sensitivity, accuracy, and reproducibility. Platform design choices that emphasize one aspect tend to do so at the expense of the others. As demonstrated in the MAQC study, Agilent Technologies’ microarray platform seeks to achieve an appropriate balance among these attributes, emphasizing accuracy and sensitivity for detection of differential expression across a wide dynamic range. Multiplex slides enable 4 individual whole genome microarrays to be printed on a single glass slide, improving both the sensitivity and reproducibility of the platform, without sacrificing the accuracy of differential expression calls.
Lucas et al. (2007) used commercially available MAQC samples to evaluate the performance of Agilent’s high-density multi-pack whole human genome arrays (4-Pack). The researchers use some of the analysis methods and metrics put forth in that study to compare the performance of the new generation, 4-Pack microarrays to the “legacy” whole genome products (44K). Using the new generation 4-Pack microarrays in conjunction with the extended Dynamic Range (XDR) feature of the Agilent microarray scanner, the group achieved improved sensitivity and dynamic range over the legacy microarray, enabling the detection of lower concentration transcripts. The group also noted dramatic improvements in detection of differential expression, not only compared to the 44K arrays, but when compared to actual MAQC results, as well. Further, when compared to TaqMan, the 4-pack microarray demonstrated high relative accuracy. When assessed in terms of the coefficient of variation (CV) to measure reproducibility, both the 4-pack and 44K arrays had median user CVs that were less than 10%, with the 4-Pack showing generally improved reproducibility attributed to the increased concentration of hybridization.
Figure 1. Spike-In concentration response.
Figure 2. Number of differentially expressed genes.
Figure 3. Correlation between microarray and TaqMan data.
Figure 4. Signal variation within user.
Figure 5. Signal variation among users.
Original Research Paper:
Title: Assessment of microarray technology using MAQC samples.
Authors: Lucas A, D’Andrade P, Chan A, Wong A, Zhou X, Corson J, Fulmer-Smentek S.
Journal: Bioscience Technology, July 2007.
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Whole Human Genome: a broad view that represents all known genes and transcripts in the human genome in a 4X44K array
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