Estimating Motifs Under Order Restrictions
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Erik W van Zwet
, Katherina J Kechris , Peter J Bickel and Michael B. Eisen
Transcription factors and many other DNA-binding proteins recognize more than one specific sequence. Among sequences recognized by a given DNA-binding protein, different positions exhibit varying degrees of conservation. The reason is that base pairs that are more extensively contacted by the protein tend to be more conserved. This observation can be used in the discovery of transcription factor binding sites. Here we present a rigorous means to accomplish this. In particular, we constrain the order of the information (entropy) in the columns of the position specific weight matrix (PWM) which characterizes the motif being sought. We then show how to compute the maximum likelihood estimate of a PWM under such order restrictions. This computation is easily integrated with the EM algorithm or the Gibbs sampler to enhance performance in the search for motifs in unaligned sequences. We demonstrate our method on a well-known data set of binding sites of the transcription factor Crp in E. coli.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Article
- Estimating Motifs Under Order Restrictions
- Reproducible Research: A Bioinformatics Case Study
- Generalized Rank Tests for Replicated Microarray Data
- Stepwise Normalization of Two-Channel Spotted Microarrays
- Comparing Automatic and Manual Image Processing in FLARE Assay Analysis for Colon Carcinogenesis
- Pixel-level Signal Modelling with Spatial Correlation for Two-Colour Microarrays
- Empirical Bayes Microarray ANOVA and Grouping Cell Lines by Equal Expression Levels
- Multiple Testing and Data Adaptive Regression: An Application to HIV-1 Sequence Data.
- Early Diagnostic Marker Panel Determination for Microarray Based Clinical Studies
- Prediction of Missing Values in Microarray and Use of Mixed Models to Evaluate the Predictors
- Combined Association and Linkage Analysis for General Pedigrees and Genetic Models
- Incorporating Biological Information as a Prior in an Empirical Bayes Approach to Analyzing Microarray Data
- The Relative Inefficiency of Sequence Weights Approaches in Determining a Nucleotide Position Weight Matrix
- A Simple Loglinear Model for Haplotype Effects in a Case-Control Study Involving Two Unphased Genotypes
- Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction
- Error Distribution for Gene Expression Data
- A General Framework for Weighted Gene Co-Expression Network Analysis
- Statistical Inference in Evolutionary Models of DNA Sequences via the EM Algorithm
- Comparing Bacterial DNA Microarray Fingerprints
- Continuous Covariates in Genetic Association Studies of Case-Parent Triads: Gene and Gene-Environment Interaction Effects, Population Stratification, and Power Analysis
- Robust Remote Homology Detection by Feature Based Profile Hidden Markov Models
- Empirical Bayes Estimation of a Sparse Vector of Gene Expression Changes
- Hierarchical Inverse Gaussian Models and Multiple Testing: Application to Gene Expression Data
- FADO: A Statistical Method to Detect Favored or Avoided Distances between Occurrences of Motifs using the Hawkes' Model
- Prediction of Genomewide Conserved Epitope Profiles of HIV-1: Classifier Choice and Peptide Representation
- Fold-Change Estimation of Differentially Expressed Genes using Mixture Mixed-Model
- Test on the Structure of Biological Sequences via Chaos Game Representation
- Reverse Engineering Galactose Regulation in Yeast through Model Selection
- Empirical Bayes and Resampling Based Multiple Testing Procedure Controlling Tail Probability of the Proportion of False Positives.
- Weighted Analysis of Paired Microarray Experiments
- A Probabilistic Approach to Large-Scale Association Scans: A Semi-Bayesian Method to Detect Disease-Predisposing Alleles
- A Shrinkage Approach to Large-Scale Covariance Matrix Estimation and Implications for Functional Genomics
- Structured Antedependence Models for Functional Mapping of Multiple Longitudinal Traits
- Correlation Between Gene Expression Levels and Limitations of the Empirical Bayes Methodology for Finding Differentially Expressed Genes
- Bayesian Statistical Studies of the Ramachandran Distribution
- On Reference Designs For Microarray Experiments
- Computing Asymptotic Power and Sample Size for Case-Control Genetic Association Studies in the Presence of Phenotype and/or Genotype Misclassification Errors
Articles in the same Issue
- Article
- Estimating Motifs Under Order Restrictions
- Reproducible Research: A Bioinformatics Case Study
- Generalized Rank Tests for Replicated Microarray Data
- Stepwise Normalization of Two-Channel Spotted Microarrays
- Comparing Automatic and Manual Image Processing in FLARE Assay Analysis for Colon Carcinogenesis
- Pixel-level Signal Modelling with Spatial Correlation for Two-Colour Microarrays
- Empirical Bayes Microarray ANOVA and Grouping Cell Lines by Equal Expression Levels
- Multiple Testing and Data Adaptive Regression: An Application to HIV-1 Sequence Data.
- Early Diagnostic Marker Panel Determination for Microarray Based Clinical Studies
- Prediction of Missing Values in Microarray and Use of Mixed Models to Evaluate the Predictors
- Combined Association and Linkage Analysis for General Pedigrees and Genetic Models
- Incorporating Biological Information as a Prior in an Empirical Bayes Approach to Analyzing Microarray Data
- The Relative Inefficiency of Sequence Weights Approaches in Determining a Nucleotide Position Weight Matrix
- A Simple Loglinear Model for Haplotype Effects in a Case-Control Study Involving Two Unphased Genotypes
- Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction
- Error Distribution for Gene Expression Data
- A General Framework for Weighted Gene Co-Expression Network Analysis
- Statistical Inference in Evolutionary Models of DNA Sequences via the EM Algorithm
- Comparing Bacterial DNA Microarray Fingerprints
- Continuous Covariates in Genetic Association Studies of Case-Parent Triads: Gene and Gene-Environment Interaction Effects, Population Stratification, and Power Analysis
- Robust Remote Homology Detection by Feature Based Profile Hidden Markov Models
- Empirical Bayes Estimation of a Sparse Vector of Gene Expression Changes
- Hierarchical Inverse Gaussian Models and Multiple Testing: Application to Gene Expression Data
- FADO: A Statistical Method to Detect Favored or Avoided Distances between Occurrences of Motifs using the Hawkes' Model
- Prediction of Genomewide Conserved Epitope Profiles of HIV-1: Classifier Choice and Peptide Representation
- Fold-Change Estimation of Differentially Expressed Genes using Mixture Mixed-Model
- Test on the Structure of Biological Sequences via Chaos Game Representation
- Reverse Engineering Galactose Regulation in Yeast through Model Selection
- Empirical Bayes and Resampling Based Multiple Testing Procedure Controlling Tail Probability of the Proportion of False Positives.
- Weighted Analysis of Paired Microarray Experiments
- A Probabilistic Approach to Large-Scale Association Scans: A Semi-Bayesian Method to Detect Disease-Predisposing Alleles
- A Shrinkage Approach to Large-Scale Covariance Matrix Estimation and Implications for Functional Genomics
- Structured Antedependence Models for Functional Mapping of Multiple Longitudinal Traits
- Correlation Between Gene Expression Levels and Limitations of the Empirical Bayes Methodology for Finding Differentially Expressed Genes
- Bayesian Statistical Studies of the Ramachandran Distribution
- On Reference Designs For Microarray Experiments
- Computing Asymptotic Power and Sample Size for Case-Control Genetic Association Studies in the Presence of Phenotype and/or Genotype Misclassification Errors