Statistical Methods in Integrative Analysis for Gene Regulatory Modules
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Lingmin Zeng
We propose a suite of statistical methods for inferring a cis-regulatory module, which is a combination of several transcription factors binding in the promoter regions to regulate gene expression. The approach is an integrative analysis that combines information from multiple types of biological data, including genomic DNA sequences, genome-wide location analysis (ChIP-chip experiments), and gene expression microarray. More specifically, we use a hidden Markov model to first predict a cluster of transcription factor binding sites in DNA sequences. The predictions are refined by regression analysis on gene expression microarray data and/or ChIP-chip binding experiments. In regression analysis, we particularly apply factor analysis, whose statistical model characterizes the modular structure of cis-regulation. When groups of coexpressed genes are available, we further apply canonical correlation analysis to infer relationships between a group of genes and their common set of transcription factors. Our approach is validated on the well-studied yeast cell cycle gene regulation. It is then used to study condition-specific regulators for a set of Ste12 target genes. The multiple data sources provide information of transcriptional regulation from different aspects. Therefore, the integrative analysis offers a fine prediction on transcriptional regulatory code and infers potential regulatory networks.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Article
- Self-Organizing Maps with Statistical Phase Synchronization (SOMPS) for Analyzing Cell Cycle-Specific Gene Expression Data
- Coalescent Time Distributions in Trees of Arbitrary Size
- Quantifying the Association between Gene Expressions and DNA-Markers by Penalized Canonical Correlation Analysis
- Nonparametric Functional Mapping of Quantitative Trait Loci Underlying Programmed Cell Death
- Accommodating Uncertainty in a Tree Set for Function Estimation
- Drifting Markov Models with Polynomial Drift and Applications to DNA Sequences
- Comparing the Characteristics of Gene Expression Profiles Derived by Univariate and Multivariate Classification Methods
- Calculating Confidence Intervals for Prediction Error in Microarray Classification Using Resampling
- Structure Learning in Nested Effects Models
- Correcting the Estimated Level of Differential Expression for Gene Selection Bias: Application to a Microarray Study
- Adapting Prediction Error Estimates for Biased Complexity Selection in High-Dimensional Bootstrap Samples
- Adaptive Choice of the Number of Bootstrap Samples in Large Scale Multiple Testing
- Re-Cracking the Nucleosome Positioning Code
- Semi-Parametric Differential Expression Analysis via Partial Mixture Estimation
- A SNP Streak Model for the Identification of Genetic Regions Identical-by-descent
- Detecting Two-Locus Gene-Gene Effects Using Monotonisation of the Penetrance Matrix
- Modeling DNA Methylation in a Population of Cancer Cells
- Phenotyping Genetic Diseases Using an Extension of µ-Scores for Multivariate Data
- The Estimator of the Optimal Measure of Allelic Association: Mean, Variance and Probability Distribution When the Sample Size Tends to Infinity
- Predicting Protein Concentrations with ELISA Microarray Assays, Monotonic Splines and Monte Carlo Simulation
- A Comparison of Normalization Techniques for MicroRNA Microarray Data
- Collapsing SNP Genotypes in Case-Control Genome-Wide Association Studies Increases the Type I Error Rate and Power
- Estimating Number of Clusters Based on a General Similarity Matrix with Application to Microarray Data
- Data Distribution of Short Oligonucleotide Expression Arrays and Its Application to the Construction of a Generalized Intellectual Framework
- Approximately Sufficient Statistics and Bayesian Computation
- A Composite-Conditional-Likelihood Approach for Gene Mapping Based on Linkage Disequilibrium in Windows of Marker Loci
- Statistical Methods in Integrative Analysis for Gene Regulatory Modules
- Reducing Spatial Flaws in Oligonucleotide Arrays by Using Neighborhood Information
- Pattern Classification of Phylogeny Signals
- A Unification of Multivariate Methods for Meta-Analysis of Genetic Association Studies
- Importance Sampling for the Infinite Sites Model
- Supervised Distance Matrices
- Addressing the Shortcomings of Three Recent Bayesian Methods for Detecting Interspecific Recombination in DNA Sequence Alignments
- A Sparse PLS for Variable Selection when Integrating Omics Data
- Software Communication
- TRAB: Testing Whether Mutation Frequencies Are Above an Unknown Background
Articles in the same Issue
- Article
- Self-Organizing Maps with Statistical Phase Synchronization (SOMPS) for Analyzing Cell Cycle-Specific Gene Expression Data
- Coalescent Time Distributions in Trees of Arbitrary Size
- Quantifying the Association between Gene Expressions and DNA-Markers by Penalized Canonical Correlation Analysis
- Nonparametric Functional Mapping of Quantitative Trait Loci Underlying Programmed Cell Death
- Accommodating Uncertainty in a Tree Set for Function Estimation
- Drifting Markov Models with Polynomial Drift and Applications to DNA Sequences
- Comparing the Characteristics of Gene Expression Profiles Derived by Univariate and Multivariate Classification Methods
- Calculating Confidence Intervals for Prediction Error in Microarray Classification Using Resampling
- Structure Learning in Nested Effects Models
- Correcting the Estimated Level of Differential Expression for Gene Selection Bias: Application to a Microarray Study
- Adapting Prediction Error Estimates for Biased Complexity Selection in High-Dimensional Bootstrap Samples
- Adaptive Choice of the Number of Bootstrap Samples in Large Scale Multiple Testing
- Re-Cracking the Nucleosome Positioning Code
- Semi-Parametric Differential Expression Analysis via Partial Mixture Estimation
- A SNP Streak Model for the Identification of Genetic Regions Identical-by-descent
- Detecting Two-Locus Gene-Gene Effects Using Monotonisation of the Penetrance Matrix
- Modeling DNA Methylation in a Population of Cancer Cells
- Phenotyping Genetic Diseases Using an Extension of µ-Scores for Multivariate Data
- The Estimator of the Optimal Measure of Allelic Association: Mean, Variance and Probability Distribution When the Sample Size Tends to Infinity
- Predicting Protein Concentrations with ELISA Microarray Assays, Monotonic Splines and Monte Carlo Simulation
- A Comparison of Normalization Techniques for MicroRNA Microarray Data
- Collapsing SNP Genotypes in Case-Control Genome-Wide Association Studies Increases the Type I Error Rate and Power
- Estimating Number of Clusters Based on a General Similarity Matrix with Application to Microarray Data
- Data Distribution of Short Oligonucleotide Expression Arrays and Its Application to the Construction of a Generalized Intellectual Framework
- Approximately Sufficient Statistics and Bayesian Computation
- A Composite-Conditional-Likelihood Approach for Gene Mapping Based on Linkage Disequilibrium in Windows of Marker Loci
- Statistical Methods in Integrative Analysis for Gene Regulatory Modules
- Reducing Spatial Flaws in Oligonucleotide Arrays by Using Neighborhood Information
- Pattern Classification of Phylogeny Signals
- A Unification of Multivariate Methods for Meta-Analysis of Genetic Association Studies
- Importance Sampling for the Infinite Sites Model
- Supervised Distance Matrices
- Addressing the Shortcomings of Three Recent Bayesian Methods for Detecting Interspecific Recombination in DNA Sequence Alignments
- A Sparse PLS for Variable Selection when Integrating Omics Data
- Software Communication
- TRAB: Testing Whether Mutation Frequencies Are Above an Unknown Background