PROTEIN INTERACTION NETWORK – INFERENCE TOOL DIVYA RAO CANDIDATE FOR MASTER OF SCIENCE IN...
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Transcript of PROTEIN INTERACTION NETWORK – INFERENCE TOOL DIVYA RAO CANDIDATE FOR MASTER OF SCIENCE IN...
PROTEIN INTERACTION NETWORK – INFERENCE TOOL
DIVYA RAOCANDIDATE FOR MASTER OF SCIENCE IN
BIOINFORMATICSADVISOR: Dr. FILIPPO MENCZER
CAPSTONE PROJECT PRESENTATIONSCHOOL OF INFORMATICS - INDIANA
UNIVERSITY April 20, 2006
Outline Outline Background PIN-IT Sample Results Future Work References Acknowledgements
• Background• PIN-IT• Sample Results• Future Work• References• Acknowledgements
April 20, 2006
Slide 2 of 19
Definitions
• Proteins are complex, high-molecular weight organic compounds
• Protein interactions are associations between protein molecules
• Examples: enzymes, hormones, transcription factors, antibodies, structural proteins
Outline Background
Definitions PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 3 of 19
Experimental Approaches
• Immunoprecipitation
Outline Background
Experiments
PIN-IT Results Future Work References Acknowledgements
http://www.molecularstation.com/protein/immunoprecipitation/
April 20, 2006
Slide 4 of 19
High Throughput Experiments
• DNA sequence analysis– Homology & Orthology– Limited to proteins encoded by a
single gene in one species or two or more genes in another
Outline Background
Experiments
PIN-IT Results Future Work References Acknowledgements
A a
Species 1
Species 2
April 20, 2006
Slide 5 of 19
a
b
B
bSpecies 3
Yeast Two Hybrid
• 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
Outline Background
Experiments PIN-IT Results Future Work References Acknowledgements
http://www.biochem.arizona.edu/classes/bioc568/bioc568.htm April 20, 2006
Slide 6 of 19
PRISM Outline Background
Other Tools PIN-IT Results Future Work References Acknowledgements
http
://go
rdio
n.hp
c.en
g.ku
.edu
.tr/p
rism
/tuto
rial.p
hp#p
redi
ctio
ns.p
hp
April 20, 2006
Slide 7 of 19
ADVICE BackgroundOther Tools
http://advice.i2r.a-star.edu.sg/doc/flowchart.gif April 20, 2006
Slide 8 of 19
Motivation
• 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
Outline Background
Motivation PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 9 of 19
Protein Interaction Network Inference Tool
• Infer protein-protein interactions– Known protein interactions– Protein similarity
Outline Background PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 10 of 19
PIN-IT Data sources• 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
Outline Background PIN-IT
Data Sources
Results Future Work References Acknowledgements
April 20, 2006
Slide 11 of 19
Outline Background PIN-IT
Data
DIP BIND PIN-IT
Number of proteins 18826 27809 43573
Number of Interactions 54172 44354 94659
Number of Organisms 109 1020 1033
PIN-IT Data
April 20, 2006
Slide 12 of 19
BLAST• 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
Outline Background PIN-IT
BLAST Results Future Work References Acknowledgements
April 20, 2006
Slide 13 of 19
Calculating Inference
AIB
xy
S
D
),(),(
),(),(),(),(
),(),(
),exp(),(
maxarg),(
1
baba
yBBAxAyx
xAxA
BABA
Dbasuggest
SISD
nES
rI
Where:
r is the false positive rate
E is the e-value from BLAST
n is the size of the dataset
April 20, 2006
Slide 14 of 19
Demo
• PIN-IT
Outline Background PIN-IT
Demo Results Future Work References Acknowledgments
April 20, 2006
Slide 15 of 19
Outline Background PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 16 of 19
Results
63225506324320
63237666321260
Interacts with mRNAs encoding membrane-associated proteins
Putative integral membrane E3 ubiquitin ligase
Putative integral membrane, negative
regulation of amino acid uptake
Has roles in maintenance of cell wall integrity
Future Work
• 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
Outline Background PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 17 of 19
References• 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
Outline Background PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 18 of 19
Acknowledgements
• Dr. Filippo Menczer• Dr. Haixu Tang• Dr. Alessandro Flammini• Dr. Sun Kim• Dr. Mehmet Dalkilic• Dr. Gary Wiggins• Linda Hostetter
Outline Background PIN-IT Results Future Work References Acknowledgements
April 20, 2006
Slide 19 of 19
Query
April 20, 2006
April 20, 2006
Query Results
Node Information
April 20, 2006
Query Results
Interaction Edge Information
April 20, 2006
April 20, 2006
Query Results
Similarity Edge Information
April 20, 2006
April 20, 2006
Query Results
Inference Edge Information
April 20, 2006