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Transcript
LinkedPPI: Enabling Intutive, Integrative Protein-Protein Interaction Discovery Laleh Kazemzadeh, Maulik R.Kamdar, Oya D.Beyan, Stefan Decker, Frank Barry 19-10-2014 Outline Introduction Motivation and Challenges Methods LinkedPPI architecture Domain-Specific Model Results Search and Visualization Use Cases Summary G B G A 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 ! Experiment! Interaction! detects! ! "System! "Type! "Scale! "ID! "Source!Database! "Score! "Modification! "Qualification! "Tags! ! ! ! ! Protein! "UniprotID! ! Gene! "EntrezID! ! hasDomain! ! left"right! DD!Interaction! "PFamID! "!Score! "Inferred!Score! partOf! hasGene! publishedIn! "Title! "Author! "Year! "Abstracts! ! ! detectedIn! left"right! Component! Organism! "Official!Symbols! "Synonyms! "Description! ! ! "TaxonomyID! "Name! ! ! Protein!Domain! "PFamID! Publication! hasComponent! Complex! "ID! "Name! "Synonyms! "Component!Synonyms! "Function!Comment! "Disease!Comment! "SubUnit!Comment! ! ! ! detectedIn! publishedIn! Ideogram! "ID!(chrm"Ideogram)! left"right! "Start! "Stop! "Gene!Count! II!Interaction! "Inferred!Score! ! Results: Search and Visualization 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. Use Case2: Identification of Potential DomainDomain 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 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
