Combining Multiple Laser Scans of Spotted Microarrays by Means of a Two-Way ANOVA Model
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Jérôme Ambroise
Motivation: Assessment of gene expression on spotted microarrays is based on measurement of fluorescence intensity emitted by hybridized spots. Unfortunately, quantifying fluorescence intensity from hybridized spots does not always correctly reflect gene expression level. Low gene expression levels produce low fluorescence intensities which tend to be confounded with the local background while high gene expression levels produce high fluorescence intensities which rapidly reach the saturation level. Most algorithms that combine data acquired at different voltages of the photomultiplier tube (PMT) assume that a change in scanner setting transforms the intensity measurements by a multiplicative constant.Methods and Results: In this paper we introduce a new model of spot foreground intensity which integrates a PMT voltage independent scanner optical bias. This new model is used to implement a ”Combining Multiple Scan using a Two-way ANOVA” (CMS2A) method, which is based on a maximum likelihood estimation of the scanner optical bias. After having computed scanner bias, coefficients of the two-way ANOVA model are used for correcting the saturated spots intensities obtained at high PMT voltage by using their counterpart values at lower PMT voltages. The method was compared to state-of-the-art multiple scan algorithms, using data generated from the MAQC study. CMS2A produced fold-changes that were highly correlated with qPCR fold-changes. As the scanner optical bias is accurately estimated within CMS2A, this method allows also avoiding fold-change compression biases whatever the value of this optical bias.
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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- Normalization, bias correction, and peak calling for ChIP-seq
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- Empirical Bayes Interval Estimates that are Conditionally Equal to Unadjusted Confidence Intervals or to Default Prior Credibility Intervals
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- Software Communication
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Articles in the same Issue
- Article
- Exploring Multicollinearity Using a Random Matrix Theory Approach
- The Beta-Binomial SGoF method for multiple dependent tests
- Detecting Sample Misidentifications in Genetic Association Studies
- Borrowing Information Across Genes and Experiments for Improved Error Variance Estimation in Microarray Data Analysis
- Hierarchical Bayes Model for Predicting Effectiveness of HIV Combination Therapies
- The practical effect of batch on genomic prediction
- Normalization, bias correction, and peak calling for ChIP-seq
- Combining Multiple Laser Scans of Spotted Microarrays by Means of a Two-Way ANOVA Model
- Empirical Bayes Interval Estimates that are Conditionally Equal to Unadjusted Confidence Intervals or to Default Prior Credibility Intervals
- Detection of Differentially Expressed Gene Sets in a Partially Paired Microarray Data Set
- Non-Iterative, Regression-Based Estimation of Haplotype Associations with Censored Survival Outcomes
- Graph Selection with GGMselect
- Sample Size Calculations for Designing Clinical Proteomic Profiling Studies Using Mass Spectrometry
- A New Approach for the Joint Analysis of Multiple Chip-Seq Libraries with Application to Histone Modification
- Software Communication
- GENOVA: Gene Overlap Analysis of GWAS Results
