A knowledge-based strategy for structural recognition of transcription factor binding sites

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A knowledge-based strategy for structural recognition of transcription factor binding sites

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A knowledge-based strategy for structural recognition of transcription factor binding sites

  1. 1. A knowledge-based strategy for structural recognition of transcription factor binding sites Beisi Xu Laboratory of Molecular Modeling and Design Dalian Institute of Chemical Physical xubeisi [at] gmail.com
  2. 2. Central Dogma http://stemcells.nih.gov
  3. 3. Central Dogma
  4. 4. Eukaryotic Model
  5. 5. Transcription wiki
  6. 6. Before Transcription
  7. 7. Yeast TFBS Database <ul><li>TRANSFAC </li></ul><ul><ul><li>Commercial </li></ul></ul><ul><ul><li>Experimental </li></ul></ul><ul><ul><li>Redundancy </li></ul></ul><ul><li>JASPAR </li></ul><ul><ul><li>Open </li></ul></ul><ul><ul><li>Only PWM </li></ul></ul><ul><ul><li>Non redundancy </li></ul></ul><ul><li>SELEX_DB & HTPSELEX </li></ul><ul><ul><li>SELEX experiment </li></ul></ul><ul><li>SCPD,MYBS </li></ul>
  8. 8. TFBS <ul><li>Conserved Sequence </li></ul><ul><ul><li>Most probability base </li></ul></ul><ul><ul><li>Lost information </li></ul></ul><ul><li>Position Weight Matrix(PWM) </li></ul>jaspar <ul><ul><li>Example: </li></ul></ul><ul><ul><li>AAAA </li></ul></ul><ul><ul><li>ACCA </li></ul></ul><ul><ul><li>ACTG AAAA </li></ul></ul><ul><ul><li>CAAC </li></ul></ul><ul><ul><li>CAGT </li></ul></ul>
  9. 9. TFBS Prediction Methods <ul><li>de novo </li></ul><ul><ul><li>MEME,AlignACE,BioProspector </li></ul></ul><ul><ul><li>MotifVoter 275% better </li></ul></ul><ul><ul><li>CisModule 56% </li></ul></ul><ul><li>Chip-array data </li></ul><ul><ul><li>Mdscan,MatrixREDUCE,RankMotif++ </li></ul></ul><ul><ul><li>MeDiChI chip-tiling </li></ul></ul><ul><ul><li>QuEST,MICSA chip-seq </li></ul></ul><ul><li>Phylogenetic Footprinting </li></ul><ul><ul><li>CompareProspector </li></ul></ul><ul><ul><li>PhyloGibbs </li></ul></ul><ul><ul><li>PhyME </li></ul></ul>
  10. 10. Reference State
  11. 11. Volume-Correction & Dirichlet pseudocounts for low-counts
  12. 12. Optimization I
  13. 13. Optimization II
  14. 14. Optimization III
  15. 15. Optimization III
  16. 16. Correction Combination Result
  17. 17. Transcription Factor Binding Sites(TFBS )
  18. 18. Prediction Process
  19. 19. Threading Energy
  20. 20. Match Experiment Result
  21. 21. DNA strucuture rotation and translation
  22. 22. Compare of training set
  23. 23. Prediction Accuracy
  24. 24. Comparing to Other Methods
  25. 25. ROC curves for MCM1
  26. 26. Energy Grid Map
  27. 27. Lower Energy Grid Map
  28. 28. Forbidden Block of Protein
  29. 29. Native Structure
  30. 31. A-DNA,B-DNA,Z-DNA

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