A knowledge-based strategy for structural

recognition of transcription factor binding sites

Beisi XuLaboratory of Molecular Modeling and Design

Dalian Institute of Chemical Physicalxubeisi [at] gmail.com

Central Dogma

http://stemcells.nih.govhttp://stemcells.nih.gov

Central Dogma

Eukaryotic Model

Transcription

wikiwiki

Before Transcription

Yeast TFBS Database

• TRANSFAC– Commercial – Experimental– Redundancy

• JASPAR– Open– Only PWM– Non redundancy

• SELEX_DB & HTPSELEX– SELEX experiment

• SCPD,MYBS

TFBS

• Conserved Sequence– Most probability base– Lost information

• Position Weight Matrix(PWM)

jasparjaspar

Example:Example:AAAAAAAAACCAACCAACTG ACTG AAAAAAAACAACCAACCAGTCAGT

TFBS Prediction Methods

• de novo• MEME,AlignACE,BioProspector• MotifVoter 275% better• CisModule 56%

• Chip-array data• Mdscan,MatrixREDUCE,RankMotif++• MeDiChI chip-tiling• QuEST,MICSA chip-seq

• Phylogenetic Footprinting• CompareProspector• PhyloGibbs• PhyME

Reference State

Volume-Correction & Dirichlet pseudocounts for low-counts

Optimization I

Optimization II

Optimization III

Optimization III

Correction Combination Result

Transcription Factor Binding Sites(TFBS )

Prediction Process

Threading Energy

Match Experiment Result

DNA strucuture rotation and translation

Compare of training set

Prediction Accuracy

Comparing to Other Methods

ROC curves for MCM1

Energy Grid Map

Lower Energy Grid Map

Forbidden Block of Protein

Native Structure

A-DNA,B-DNA,Z-DNA