Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays
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Conrad J Burden
Recent analyses have shown that the relationship between intensity measurements from high density oligonucleotide microarrays and known concentration is non linear. Thus many measurements of so-called gene expression are neither measures of transcript nor mRNA concentration as might be expected.Intensity as measured in such microarrays is a measurement of fluorescent dye attached to probe-target duplexes formed during hybridization of a sample to the probes on the microarray. We develop several dynamic adsorption models relating fluorescent dye intensity to target RNA concentration, the simplest of which is the equilibrium Langmuir isotherm, or hyperbolic response function. Using data from the Affymerix HG-U95A Latin Square experiment, we evaluate various physical models, including equilibrium and non-equilibrium models, by applying maximum likelihood methods. We show that for these data, equilibrium Langmuir isotherms with probe dependent parameters are appropriate. We describe how probe sequence information may then be used to estimate the parameters of the Langmuir isotherm in order to provide an improved measure of absolute target concentration.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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- Relating HIV-1 Sequence Variation to Replication Capacity via Trees and Forests
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
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- Using Importance Sampling to Improve Simulation in Linkage Analysis
- Model-Based Assignment and Inference of Protein Backbone Nuclear Magnetic Resonances
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- Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma
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- Combining Nearest Neighbor Classifiers Versus Cross-Validation Selection
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- Multiple Testing. Part II. Step-Down Procedures for Control of the Family-Wise Error Rate
- Augmentation Procedures for Control of the Generalized Family-Wise Error Rate and Tail Probabilities for the Proportion of False Positives
- Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data
- A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects
- Deletion/Substitution/Addition Algorithm in Learning with Applications in Genomics
- Classifying Gene Expression Profiles from Pairwise mRNA Comparisons
- Hierarchical Bayesian Neural Network for Gene Expression Temporal Patterns
- A Mixed Model Approach to Identify Yeast Transcriptional Regulatory Motifs via Microarray Experiments
- Mammalian Genomes Ease Location of Human DNA Functional Segments but Not Their Description
- On the Dependence Structure of Sequence Alignment Scores Calculated with Multiple Scoring Matrices
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- A Method for Evaluating the Impact of Individual Haplotypes on Disease Incidence in Molecular Epidemiology Studies
- Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment
- MergeMaid: R Tools for Merging and Cross-Study Validation of Gene Expression Data
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- Maximum Likelihood for Genome Phylogeny on Gene Content
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