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PROTEIN INTERACTION NETWORK – INFERENCE TOOL

PROTEIN INTERACTION NETWORK – INFERENCE TOOL. DIVYA RAO CANDIDATE FOR MASTER OF SCIENCE IN BIOINFORMATICS ADVISOR: Dr. FILIPPO MENCZER CAPSTONE PROJECT PRESENTATION SCHOOL OF INFORMATICS - INDIANA UNIVERSITY. April 20, 2006. Outline Background PIN-IT Sample Results Future Work

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PROTEIN INTERACTION NETWORK – INFERENCE TOOL

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  1. PROTEIN INTERACTION NETWORK – INFERENCE TOOL DIVYA RAO CANDIDATE FOR MASTER OF SCIENCE IN BIOINFORMATICS ADVISOR: Dr. FILIPPO MENCZER CAPSTONE PROJECT PRESENTATION SCHOOL OF INFORMATICS - INDIANA UNIVERSITY April 20, 2006

  2. Outline • Background • PIN-IT • Sample Results • Future Work • References • Acknowledgements Outline • Background • PIN-IT • Sample Results • Future Work • References • Acknowledgements Slide 2 of 19 April 20, 2006

  3. Definitions • Outline • Background • Definitions • PIN-IT • Results • Future Work • References • Acknowledgements • Proteins are complex, high-molecular weight organic compounds • Protein interactions are associations between protein molecules • Examples: enzymes, hormones, transcription factors, antibodies, structural proteins Slide 3 of 19 April 20, 2006

  4. Experimental Approaches • Outline • Background • Experiments • PIN-IT • Results • Future Work • References • Acknowledgements • Immunoprecipitation http://www.molecularstation.com/protein/immunoprecipitation/ Slide 4 of 19 April 20, 2006

  5. High Throughput Experiments • Outline • Background • Experiments • PIN-IT • Results • Future Work • References • Acknowledgements • DNA sequence analysis • Homology & Orthology • Limited to proteins encoded by a single gene in one species or two or more genes in another a A b Species 2 B a b Species 1 Species 3 Slide 5 of 19 April 20, 2006

  6. Yeast Two Hybrid • Outline • Background • Experiments • PIN-IT • Results • Future Work • References • Acknowledgements • Bait & prey • Transcription: DNA -> RNA • Two haploid yeasts • Benefit: • yeast can express genes from almost any species • Limitation: • Mutations – false positives • May not detect weak or rapid interactions Slide 6 of 19 April 20, 2006 http://www.biochem.arizona.edu/classes/bioc568/bioc568.htm

  7. PRISM • Outline • Background • Other Tools • PIN-IT • Results • Future Work • References • Acknowledgements http://gordion.hpc.eng.ku.edu.tr/prism/tutorial.php#predictions.php Slide 7 of 19 April 20, 2006

  8. ADVICE • Background • Other Tools http://advice.i2r.a-star.edu.sg/doc/flowchart.gif Slide 8 of 19 April 20, 2006

  9. Motivation • Outline • Background • Motivation • PIN-IT • Results • Future Work • References • Acknowledgements • Interaction maps can be used to reveal drug targets • BCL6 in humans causes B-cell non-Hodgkin lymphoma. In the fruitfly the BCL6 ortholog binds calcineurin phosphatases • Hubs vs. peripheral proteins Slide 9 of 19 April 20, 2006

  10. Protein Interaction Network Inference Tool • Outline • Background • PIN-IT • Results • Future Work • References • Acknowledgements • Infer protein-protein interactions • Known protein interactions • Protein similarity Slide 10 of 19 April 20, 2006

  11. PIN-IT Data sources • Outline • Background • PIN-IT • Data Sources • Results • Future Work • References • Acknowledgements • Database of Interacting Proteins (DIP) • Biomolecular Interaction Network Database (BIND) • Proteins with GI numbers, Taxon ID & experimental source • False positive rate • Immunoprecipitation, r = 0.1 • Yeast Two Hybrid, r = 0.6 Slide 11 of 19 April 20, 2006

  12. PIN-IT Data • Outline • Background • PIN-IT • Data Slide 12 of 19 April 20, 2006

  13. BLAST • Outline • Background • PIN-IT • BLAST • Results • Future Work • References • Acknowledgements • Basic Local Alignment Search Tool ..AGTTAC.. I I I I ..ACTTAG.. • Smith-Waterman algorithm • E-value • # of different alignments with scores equivalent to or better than S that are expected to occur in a database by chance • Orthologus proteins • BLASTP Slide 13 of 19 April 20, 2006

  14. Calculating Inference B A I S y D x Where: r is the false positive rate E is the e-value from BLAST n is the size of the dataset Slide 14 of 19 April 20, 2006

  15. Demo • Outline • Background • PIN-IT • Demo • Results • Future Work • References • Acknowledgments • PIN-IT Slide 15 of 19 April 20, 2006

  16. Results • Outline • Background • PIN-IT • Results • Future Work • References • Acknowledgements Interacts with mRNAs encoding membrane-associated proteins Putative integral membrane E3 ubiquitin ligase 6324320 6322550 6321260 6323766 Has roles in maintenance of cell wall integrity Putative integral membrane, negative regulation of amino acid uptake Slide 16 of 19 April 20, 2006

  17. Future Work • Outline • Background • PIN-IT • Results • Future Work • References • Acknowledgements • Allow for the user to upload their protein sequences and interactions • Better estimation of experimental false positive rates • Work with biologists to validate the tool and fine-tune the parameters Slide 17 of 19 April 20, 2006

  18. References • Outline • Background • PIN-IT • Results • Future Work • References • Acknowledgements • Campbell, M. A., Heyer, L.A. Discovering Genomics, Proteomics & Bioinformatics. India: Pearson Education, 2004, pp176-183. • Ito T, et al.: "A comprehensive two-hybrid analysis to explore the yeast protein interactome,".Proc Natl Acad Sci 2001, 98:4569-74. • Titz B, et al.: "What do we learn from high-throughput protein interaction data?".Expert Rev Proteomics 2004, 1:111-21. • Giot L, et al.: "A protein interaction map of Drosophila melanogaster,".Science 2003 302: 1727-1736 • Aytuna,A.S, Gursoy,A. Keskin,O., (2005). Prediction of protein-protein interactions by combining structure and sequence conservation in protein interfaces.Bioinformatics 21(12):2850-2855 • Tan, Soon-Heng, Zhang, Zhuo, Ng, See-KiongADVICE: Automated Detection and Validation of Interaction by Co-EvolutionNucl. Acids Res. 2004 32: W69-72 • Protein Interactions by Structural Matching (PRISM): http://gordion.hpc.eng.ku.edu.tr/prism/index.php • Automated Detection and Validation of Interaction by Co-Evolution (ADVICE): http://advice.i2r.a-star.edu.sg/ • DIP: http://dip.doe-mbi.ucla.edu/ • BIND: http://www.bind.ca/Action • Immunoprecipitation Image: http://www.molecularstation.com/protein/immunoprecipitation/ • Yeast Two Hybrid system image: http://www.biochem.arizona.edu/classes/bioc568/bioc568.htm Slide 18 of 19 April 20, 2006

  19. Acknowledgements • Outline • Background • PIN-IT • Results • Future Work • References • Acknowledgements • Dr. Filippo Menczer • Dr. Haixu Tang • Dr. Alessandro Flammini • Dr. Sun Kim • Dr. Mehmet Dalkilic • Dr. Gary Wiggins • Linda Hostetter Slide 19 of 19 April 20, 2006

  20. Query April 20, 2006

  21. Query Results April 20, 2006

  22. Node Information

  23. Query Results April 20, 2006

  24. Interaction Edge Information April 20, 2006

  25. Query Results April 20, 2006

  26. Similarity Edge Information April 20, 2006

  27. Query Results April 20, 2006

  28. Inference Edge Information April 20, 2006

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