LinkedPPI: Enabling Intutive, Integrative Protein-Protein Interaction Discovery

Laleh Kazemzadeh, Maulik R.Kamdar, Oya D.Beyan,Stefan Decker, Frank Barry

19-10-2014

Outline

IntroductionMotivation and Challenges

MethodsLinkedPPI architectureDomain-Specific Model

ResultsSearch and VisualizationUse Cases

Summary

GA

GB

PA

PB

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”

Method: LinkedPPI Architecture

Data Source Ineraction # Interactions # Triples

BioGRID Protein-Protein 634996 11357231

CORUM Complex 2867 156364

3did Domain-Domain 61582 320690

Domain-Specific Model

Results: Search and Visualization

Use case1: Extraction of Protein-Protein Interaction Based on Domain-Domain Interactions

Let’s Assume a single protein e.g. HES1Q1: 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.

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

HLHList 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

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

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

Thank you