Validation in Genomics: CpG Island Methylation Revisited
-
Mark R Segal
In a recent article in PLoS Genetics, Bock et al., (2006) undertake an extensive computational epigenetics analysis of the ability of DNA sequence-derived features, capturing attributes such as tetramer frequencies, repeats and predicted structure, to predict the methylation status of CpG islands. Their suite of analyses appears highly rigorous with regard to accompanying validation procedures, employing stringent Bonferroni corrections, stratified cross-validation, and follow-up experimental verification. Here, however, we showcase concerns with the validation steps, in part ascribable to the genome scale of the investigation, that serve as a cautionary note and indicate the heightened need for careful selection of analytic and companion validation methods. A series of new analyses of the same CpG island methylation data helps illustrate these issues, not just for this particular study, but also analogous investigations involving high-dimensional predictors with complex between-feature dependencies.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Article
- Low-Order Conditional Independence Graphs for Inferring Genetic Networks
- A Generalized Clustering Problem, with Application to DNA Microarrays
- A Bayes Regression Approach to Array-CGH Data
- Statistical Selection of Maintenance Genes for Normalization of Gene Expressions
- Predicting the Strongest Domain-Domain Contact in Interacting Protein Pairs
- Dimension Reduction for Classification with Gene Expression Microarray Data
- A New Type of Stochastic Dependence Revealed in Gene Expression Data
- A New Order Estimator for Fixed and Variable Length Markov Models with Applications to DNA Sequence Similarity
- Quality Optimised Analysis of General Paired Microarray Experiments
- Issues of Processing and Multiple Testing of SELDI-TOF MS Proteomic Data
- Cross-Validated Bagged Prediction of Survival
- Treatment of Uninformative Families in Mean Allele Sharing Tests for Linkage
- Quantile-Function Based Null Distribution in Resampling Based Multiple Testing
- Combining Results of Microarray Experiments: A Rank Aggregation Approach
- Model Selection for Mixtures of Mutagenetic Trees
- Pseudo-likelihood for Non-reversible Nucleotide Substitution Models with Neighbour Dependent Rates
- A Method to Increase the Power of Multiple Testing Procedures Through Sample Splitting
- Bayesian Hierarchical Model for Correcting Signal Saturation in Microarrays Using Pixel Intensities
- Using Complexity for the Estimation of Bayesian Networks
- Detecting Local High-Scoring Segments: a First-Stage Approach for Genome-Wide Association Studies
- Examining Protein Structure and Similarities by Spectral Analysis Technique
- Parameter Estimation for the Exponential-Normal Convolution Model for Background Correction of Affymetrix GeneChip Data
- Approximate Sample Size Calculations with Microarray Data: An Illustration
- Numerical Solutions for Patterns Statistics on Markov Chains
- A Heuristic Bayesian Method for Segmenting DNA Sequence Alignments and Detecting Evidence for Recombination and Gene Conversion
- A Two-Step Multiple Comparison Procedure for a Large Number of Tests and Multiple Treatments
- Validation in Genomics: CpG Island Methylation Revisited
- An Improved Nonparametric Approach for Detecting Differentially Expressed Genes with Replicated Microarray Data
- Letter to the Editor
- Treating Expression Levels of Different Genes as a Sample in Microarray Data Analysis: Is it Worth a Risk?
- Reader's Reaction
- Reader's Reaction to "Dimension Reduction for Classification with Gene Expression Microarray Data" by Dai et al (2006)
Articles in the same Issue
- Article
- Low-Order Conditional Independence Graphs for Inferring Genetic Networks
- A Generalized Clustering Problem, with Application to DNA Microarrays
- A Bayes Regression Approach to Array-CGH Data
- Statistical Selection of Maintenance Genes for Normalization of Gene Expressions
- Predicting the Strongest Domain-Domain Contact in Interacting Protein Pairs
- Dimension Reduction for Classification with Gene Expression Microarray Data
- A New Type of Stochastic Dependence Revealed in Gene Expression Data
- A New Order Estimator for Fixed and Variable Length Markov Models with Applications to DNA Sequence Similarity
- Quality Optimised Analysis of General Paired Microarray Experiments
- Issues of Processing and Multiple Testing of SELDI-TOF MS Proteomic Data
- Cross-Validated Bagged Prediction of Survival
- Treatment of Uninformative Families in Mean Allele Sharing Tests for Linkage
- Quantile-Function Based Null Distribution in Resampling Based Multiple Testing
- Combining Results of Microarray Experiments: A Rank Aggregation Approach
- Model Selection for Mixtures of Mutagenetic Trees
- Pseudo-likelihood for Non-reversible Nucleotide Substitution Models with Neighbour Dependent Rates
- A Method to Increase the Power of Multiple Testing Procedures Through Sample Splitting
- Bayesian Hierarchical Model for Correcting Signal Saturation in Microarrays Using Pixel Intensities
- Using Complexity for the Estimation of Bayesian Networks
- Detecting Local High-Scoring Segments: a First-Stage Approach for Genome-Wide Association Studies
- Examining Protein Structure and Similarities by Spectral Analysis Technique
- Parameter Estimation for the Exponential-Normal Convolution Model for Background Correction of Affymetrix GeneChip Data
- Approximate Sample Size Calculations with Microarray Data: An Illustration
- Numerical Solutions for Patterns Statistics on Markov Chains
- A Heuristic Bayesian Method for Segmenting DNA Sequence Alignments and Detecting Evidence for Recombination and Gene Conversion
- A Two-Step Multiple Comparison Procedure for a Large Number of Tests and Multiple Treatments
- Validation in Genomics: CpG Island Methylation Revisited
- An Improved Nonparametric Approach for Detecting Differentially Expressed Genes with Replicated Microarray Data
- Letter to the Editor
- Treating Expression Levels of Different Genes as a Sample in Microarray Data Analysis: Is it Worth a Risk?
- Reader's Reaction
- Reader's Reaction to "Dimension Reduction for Classification with Gene Expression Microarray Data" by Dai et al (2006)