An Internal Calibration Method for Protein-Array Studies
-
Don Simone Daly
Nuisance factors in a protein-array study add obfuscating variation to spot intensity measurements, diminishing the accuracy and precision of protein concentration predictions. The effects of nuisance factors may be reduced by design of experiments, and by estimating and then subtracting nuisance effects. Estimated nuisance effects also inform about the quality of the study and suggest refinements for future studies.We demonstrate a method to reduce nuisance effects by incorporating a non-interfering internal calibration in the study design and its complemental analysis of variance. We illustrate this method by applying a chip-level internal calibration in a biomarker discovery study.The variability of sample intensity estimates was reduced 16% to 92% with a median of 58%; confidence interval widths were reduced 8% to 70% with a median of 35%. Calibration diagnostics revealed processing nuisance trends potentially related to spot print order and chip location on a slide.The accuracy and precision of a protein-array study may be increased by incorporating a non-interfering internal calibration. Internal calibration modeling diagnostics improve confidence in study results and suggest process steps that may need refinement. Though developed for our protein-array studies, this internal calibration method is applicable to other targeted array-based studies.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Article
- Epistatic Interactions
- Testing for Gene-Gene Interaction with AMMI Models
- A Bayesian Hierarchical Model for Quantitative Real-Time PCR Data
- Informative or Noninformative Calls for Gene Expression: A Latent Variable Approach
- Detecting Genotyping Error Using Measures of Degree of Hardy-Weinberg Disequilibrium
- Optimisation of HMM Topologies Enhances DNA and Protein Sequence Modelling
- The Apportionment of Total Genetic Variation by Categorical Analysis of Variance
- Dealing with Heterogeneity between Cohorts in Genomewide SNP Association Studies
- An Empirical Bayesian Method for Estimating Biological Networks from Temporal Microarray Data
- Parameter Estimation in Multiple-Hidden I.I.D. Models from Biological Multiple Alignment
- Asymptotic Distribution of the "Orthogonal" Quantitative Transmission Disequilibrium Test in a Structured Population: Exact Formula
- Comparing Spatial Maps of Human Population-Genetic Variation Using Procrustes Analysis
- An Internal Calibration Method for Protein-Array Studies
- Weighted-LASSO for Structured Network Inference from Time Course Data
- Trilocus Disequilibrium Analysis of Multiallelic Markers in Outcrossing Populations
- Sparse Partial Least Squares Classification for High Dimensional Data
- Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases
- Sub-Modular Resolution Analysis by Network Mixture Models
- Space Oriented Rank-Based Data Integration
- The Generalized Odds Ratio as a Measure of Genetic Risk Effect in the Analysis and Meta-Analysis of Association Studies
- Network Enrichment Analysis in Complex Experiments
- Shrinkage Estimation of Effect Sizes as an Alternative to Hypothesis Testing Followed by Estimation in High-Dimensional Biology: Applications to Differential Gene Expression
- Buckley-James Boosting for Survival Analysis with High-Dimensional Biomarker Data
- A Random Coefficients Model for Regional Co-Expression Associated with DNA Copy Number
- Locating Multiple Interacting Quantitative Trait Loci with the Zero-Inflated Generalized Poisson Regression
- Classification of Genomic Sequences via Wavelet Variance and a Self-Organizing Map with an Application to Mitochondrial DNA
- Confidently Estimating the Number of DNA Replication Origins
- Generalizing Moving Averages for Tiling Arrays Using Combined P-Value Statistics
- Lasso Logistic Regression, GSoft and the Cyclic Coordinate Descent Algorithm: Application to Gene Expression Data
- Granger Causality Analysis of Human Cell-Cycle Gene Expression Profiles
- Mapping Quantitative Trait Loci in a Non-Equilibrium Population
- On the Optimal Design of Genetic Variant Discovery Studies
- On Optimal Selection of Summary Statistics for Approximate Bayesian Computation
- Assessment of LD Matrix Measures for the Analysis of Biological Pathway Association
- Optimal Tests Shrinking Both Means and Variances Applicable to Microarray Data Analysis
- The Detection of Blur in Affymetrix GeneChips
- Regression-Based Multi-Trait QTL Mapping Using a Structural Equation Model
- Spatial Clustering of Array CGH Features in Combination with Hierarchical Multiple Testing
- Predicting Patient Survival from Longitudinal Gene Expression
- Including Probe-Level Measurement Error in Robust Mixture Clustering of Replicated Microarray Gene Expression
- Reader's Reaction
- An Alternative Model of Type A Dependence in a Gene Set of Correlated Genes
- Letter to the Editor
- Permutation P-values Should Never Be Zero: Calculating Exact P-values When Permutations Are Randomly Drawn
Articles in the same Issue
- Article
- Epistatic Interactions
- Testing for Gene-Gene Interaction with AMMI Models
- A Bayesian Hierarchical Model for Quantitative Real-Time PCR Data
- Informative or Noninformative Calls for Gene Expression: A Latent Variable Approach
- Detecting Genotyping Error Using Measures of Degree of Hardy-Weinberg Disequilibrium
- Optimisation of HMM Topologies Enhances DNA and Protein Sequence Modelling
- The Apportionment of Total Genetic Variation by Categorical Analysis of Variance
- Dealing with Heterogeneity between Cohorts in Genomewide SNP Association Studies
- An Empirical Bayesian Method for Estimating Biological Networks from Temporal Microarray Data
- Parameter Estimation in Multiple-Hidden I.I.D. Models from Biological Multiple Alignment
- Asymptotic Distribution of the "Orthogonal" Quantitative Transmission Disequilibrium Test in a Structured Population: Exact Formula
- Comparing Spatial Maps of Human Population-Genetic Variation Using Procrustes Analysis
- An Internal Calibration Method for Protein-Array Studies
- Weighted-LASSO for Structured Network Inference from Time Course Data
- Trilocus Disequilibrium Analysis of Multiallelic Markers in Outcrossing Populations
- Sparse Partial Least Squares Classification for High Dimensional Data
- Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases
- Sub-Modular Resolution Analysis by Network Mixture Models
- Space Oriented Rank-Based Data Integration
- The Generalized Odds Ratio as a Measure of Genetic Risk Effect in the Analysis and Meta-Analysis of Association Studies
- Network Enrichment Analysis in Complex Experiments
- Shrinkage Estimation of Effect Sizes as an Alternative to Hypothesis Testing Followed by Estimation in High-Dimensional Biology: Applications to Differential Gene Expression
- Buckley-James Boosting for Survival Analysis with High-Dimensional Biomarker Data
- A Random Coefficients Model for Regional Co-Expression Associated with DNA Copy Number
- Locating Multiple Interacting Quantitative Trait Loci with the Zero-Inflated Generalized Poisson Regression
- Classification of Genomic Sequences via Wavelet Variance and a Self-Organizing Map with an Application to Mitochondrial DNA
- Confidently Estimating the Number of DNA Replication Origins
- Generalizing Moving Averages for Tiling Arrays Using Combined P-Value Statistics
- Lasso Logistic Regression, GSoft and the Cyclic Coordinate Descent Algorithm: Application to Gene Expression Data
- Granger Causality Analysis of Human Cell-Cycle Gene Expression Profiles
- Mapping Quantitative Trait Loci in a Non-Equilibrium Population
- On the Optimal Design of Genetic Variant Discovery Studies
- On Optimal Selection of Summary Statistics for Approximate Bayesian Computation
- Assessment of LD Matrix Measures for the Analysis of Biological Pathway Association
- Optimal Tests Shrinking Both Means and Variances Applicable to Microarray Data Analysis
- The Detection of Blur in Affymetrix GeneChips
- Regression-Based Multi-Trait QTL Mapping Using a Structural Equation Model
- Spatial Clustering of Array CGH Features in Combination with Hierarchical Multiple Testing
- Predicting Patient Survival from Longitudinal Gene Expression
- Including Probe-Level Measurement Error in Robust Mixture Clustering of Replicated Microarray Gene Expression
- Reader's Reaction
- An Alternative Model of Type A Dependence in a Gene Set of Correlated Genes
- Letter to the Editor
- Permutation P-values Should Never Be Zero: Calculating Exact P-values When Permutations Are Randomly Drawn