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Nonparametric Modeling
- f Regulatory Network
of Regulatory Network Ping Ma Department of Statistics & - - PowerPoint PPT Presentation
of Regulatory Network Ping Ma Department of Statistics & - - PowerPoint PPT Presentation
Nonparametric Modeling of Regulatory Network Ping Ma Department of Statistics & Institute for Genomic Biology University of Illinois Urbana-Champaign Central Dogma of Molecular Biology Transcription Regulation Gene A Gene B TF TF
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Transcription Regulation
Transcription factors (regulatory proteins) bind to genes, turning on or shutting off their expressions.
……TTCGA…….CCCGG……CCCGG…..CGCGGGCTTACGATATAACG
TF A TF B
Gene C
Gene A Gene B
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Transcription Factor Binding
Transcription Factor Binding Motif (TFBM):
Common patterns in DNA sequences at transcription factor binding sites. RAP1 GCN4
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Transcription Factor Binding
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Transcription Factor Binding
Mardis Nat
- Meth. 2007
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Gene Expression
To quantify the abundance of each transcript Two approaches:
Hybridization (Microarray) Sequence (RNA-Seq)
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Linking gene expression with TF binding
Linear Regression
Motif Regressor (Conlon et al 2003 PNAS) Motif Express (Zamdborg and Ma 2009 NAR)
Nonlinear Regression
RSIR (Zhong et al 2005, Bioinformatics) Correlation Pursuit (Zhong et al 2012, JRSSB)
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Converting Gene Expression to Clusters
Gene expression is noisy Clustering gene expression to get robust clusters Linking gene clusters with TF binding data.
Bayesian Network (Beer and Tavazoie 2004 Cell) Proportional Odds Model (Yuan et al 2007 PLoS Comput. Biol.)
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Desirable Features
Flexible function form to link gene expression
(clusters) with TF binding
Integration of new expression data
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Our Method
Gene expression clusters and TF binding
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Penalized Likelihood
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Functional ANOVA
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Penalized Likelihood
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Inference
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Bayesian Confidence Interval
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Mixed Effect Models
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Software
R package gss
http://cran.r-project.org/web/packages/gss/
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