1. Discovery and Dissemination
PROTEIN-PROTEIN INTERACTIONS
Madhavi Ganapathiraju
Assistant Professor
Department of Biomedical Informatics
University of Pittsburgh
Faculty of
Biomedical Informatics Training Program
Intelligent Systems Program
Integrated Systems Biology Program
Joint CMU-Pitt Ph.D. Program in Comp Bio
Language Technologies Institute (CMU)

2. ? Protein-Protein Interactions Theme of Research in Madhavi’s Lab
Central to all biological processes and structural scaffolds
The network is a medium for systems biology research
But 90% of protein-protein interactions are unknown today ?
~22,500 protein-coding genes
Human Interactome
200,000 to 600,000 PPIs
protein-pairs
~250Million possible pairs
Our primary research is in predicting protein-protein interactions.
I say high confidence, because we want to predict with very high accuracy even if we predict only a few of all true interactions
Let’s look at the size of the problem in rough numbers
There are some genes in human
If you look at proteins from every pair of these genes,
There are more than 300 million pairs
Of these only 200 to 600 thousand pairs are interacting proteins
And of these, nearly 90% of the interactions are unknown
Theme of Research in Madhavi’s Lab
Discovery of protein-protein interactions from large data sources using Machine Learning methods
Results: 1000’s of Novel PPIs discovered Accurately
(c) Madhavi Ganapathiraju

3. We discovered 1000’s of Novel PPIs Accurately
14 studied by experiments (by collaborators); all 14 validated to be correct

4. Interactome Analysis of Disease-Associated Genes
Shortest Paths between CHD Genes: Mean distance: 4.7; St-dev: 3.3
Between Random Genes: Mean: 14.9;   S-dev:   4.9
CHD Gene
Novel Predicted Interaction
Previously Known Interaction
Immunity, 40(6), Zhu et al.
Nature, 521(7553), Li et al.
Other Ongoing Studies
Cilia interactome, Schizophrenia interactome &
HMGB1 interactions
& Development of tools and algorithms for analysis and dissemination of these novel PPIs
Reveals novel relations to Cilia and to relevant pathways
Funding: BRAINS Award 1R01MH ($1.79M) & its supplement: 3R01MH (144k)
Interactome of Congenital Heart Associated Genes
and its overlap with cilia genes