a knowledge-based strategy for structural recognition of transcription factor binding sites
DESCRIPTION
A knowledge-based strategy for structural recognition of transcription factor binding sitesTRANSCRIPT
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
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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)
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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