1. LinkedPPI: Enabling Intutive, Integrative Protein-Protein Interaction Discovery Laleh Kazemzadeh, Maulik R.Kamdar, Oya D.Beyan, Stefan Decker, Frank Barry 19-10-2014

2. Outline Introduction Motivation and Challenges Methods LinkedPPI architecture Domain-Specific Model Results Search and Visualization Use Cases Summary

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5. Challenges Human genome contains 20000 protein coding genes Number of binary interaction 2^20000 Incomplete knowledge of the underlying networks What we don’t know that we don’t know Massive amount of data with too many “standards”

6. Method: LinkedPPI Architecture Data SourceIneraction# Interactions# Triples BioGRIDProtein-Protein63499611357231 CORUMComplex2867156364 3didDomain-Domain61582320690

7. Domain-Specific Model

8. Results: Search and Visualization

9. Use case1: Extraction of Protein-Protein Interaction Based on Domain-Domain Interactions Let’s Assume a single protein e.g. HES1 Q1: What are the potential interacting partners? What we know: It contains a protein domain called Hairy_orange We know Hairy_orange’s interacting domains What we can retrieve: List of proteins that contains the protein domains which are known to be Hairy_orange interacting domains.

10. Use Case2: Identification of Potential Domain- Domain Interaction Let’s assume a protein domain e.g. HLH Q2: What are its interacting domains? What we know: List of validated domain partners for HLH List of validated protein pairs which contains HLH What we can retrieve: One-to-One domain interaction for HLH One-to-Many domain interactions for HLH

11. Use Case3: Identification of Selective Interactions between Segments of Human Genome Biological Facts: Chromosomes are folded in territory Genes in closer proximity tends to be co-expressed Interacting proteins tend to have common functionality What we have: List of validated protein interactions Genomic location of each protein (start and stop position of the coding gene) What we can infer: The frequency in which each two segments of genome appear to be interacting

12. Summary  Domain-Specific Model  Search and Visualization  3 Use Cases  Link to the public Endpoints(e.g.EBI)  Statistical Analysis on the Significance of the Results  Classification of Interacting and non-Interacting Pairs

13. Thank you