Protein-protein interaction networks
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Protein-protein interaction networks
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Protein-protein interaction networks
- 2. Outline • Introduc4on to Interac4on Networks • Basic components of an interac4on network • Types of interac4on networks • Predic4ng Protein‐Protein Interac4on Networks • Methods » Logic and concept • Available Interac4on data • Integrated protein‐protein interac4on databases • Searching for interac4on data • Network Visualiza4on and Analysis tools • Popular visualiza4on tools • Network analysis • Demonstra4on • Predic4on of interac4on (PPI…?) network from microarray (ARACNE) • Visualiza4on and analysis of the predicted network (Cytoscape)
- 3. • Nodes – DNA/RNA/Protein/Metabolite • Edges Directed – Dis4nc4on between source and target » Ac4va4on (direct/indirect) » Repression (direct/indirect) Undirected – No dis4nc4on between source and target » Co‐expression (indirect) » Binding (direct) Interac-on Networks – Basic Components
- 4. Interac-on Networks ‐ Basic Features • Degree • Number of connec4ons that a node has • Distance • Number of connec4ons between two nodes, in a shortest path • Path • A sequence of connec4ons • Is there a path (reachability) • Mean Shortest Path distance (closeness) • In how many shortest paths (betweenness)
- 5. • Size of a network (Number of nodes) • Density of a network (Propor4on of the connec4ons) • Mo4fs/Cliques/Clusters/Sub‐networks Loops Chains Parallels Multi-input Single input Interac-on Networks ‐ Basic Features
- 6. Types of Interac-on Networks • DNA‐Protein » Transcrip4onal regulatory networks » Methyla4on networks • RNA‐RNA » miRNA regulatory networks • RNA‐Protein » Splicing regulatory networks • Protein‐Protein » Co‐expression networks » Co‐localiza4on networks » Co‐evolu4on networks » Structure networks » Pathway networks » Protease regulatory networks » Signal transduc4on networks » Gene Ontology networks
- 7. Single gene – Regulators/Co‐regulators – Upstream/Downstream elements in the network – Global connec4vity/interconnec4vity – Func4onal features – Differen4ally expressed subnetworks – One gene – one disease : bunch of genes – pathways – Nextgen sequencing data List of genes Why Build/Analyze Interac-on Networks ?
- 8. Outline • Introduc4on to Interac4on Networks • Basic components of an interac4on network • Types of interac4on networks • Predic4ng Protein‐Protein Interac4on Networks • Methods » Logic and concept • Available Interac4on data • Integrated protein‐protein interac4on databases • Searching for interac4on data • Network Visualiza4on and Analysis tools • Popular visualiza4on tools • Network analysis • Demonstra4on • Predic4on of interac4on (PPI…?) network from microarray (ARACNE) • Visualiza4on and analysis of the predicted network (Cytoscape)
- 9. How to Build Interac-on Networks ? • Search/Retrieve from knowledge bases • Predict from genome sequences • Predict from “omics” data • Predict from literature • Integrate and analyze
- 10. Protein Engineering, Vol. 14, No. 9, 609-614, September 2001 Predic-on from genome sequences • Gene neighbor (gene cluster, gene order) • Gene fusion (Rosea stone) • Phylogene4c profiling • Co‐evolu4on • Mirror tree
- 11. Predic-on from “omics” data • Co‐expression (Correla4on, Mutual Informa4on) • Integrated (Classifica4on) • Literature mining (Natural Language Processing)
- 12. Outline • Introduc4on to Interac4on Networks • Basic components of an interac4on network • Types of interac4on networks • Predic4ng Protein‐Protein Interac4on Networks • Methods » Logic and concept • Available Interac4on data • Integrated protein‐protein interac4on databases • Searching for interac4on data • Network Visualiza4on and Analysis tools • Popular visualiza4on tools • Network analysis • Demonstra4on • Predic4on of interac4on (PPI…?) network from microarray (ARACNE) • Visualiza4on and analysis of the predicted network (Cytoscape)
- 13. Available Interac-on Data • MINT • Molecular Interac4on Database • BIND • Biomolecular Interac4on Network Database • DIP • Database of Interac4ng Proteins • IntAct • InterAc4on Database at EBI
- 14. Integrated Data Sources • Pathway Commons • BioGRID • MiMI (Michigan Molecular Interac4ons) • STRING (Search Tool for Retrieval of Interac4ng Genes/Proteins) • Genes2Network • VisANT (Integra4ve Visual Analysis Tool) • BIOBASE • IPA (Ingenuity Pathway Analysis) • MetaCore Open Source Proprietary
- 15. IP3Rs • Inositol triphosphate receptor • ip3r1 • ip3r2 • ip3r3 » Calcium ion channels » ER • s4m1 (stromal interac4on molecule 1) » PM » Calcium sensor protein • orai1 (calcium release ac4vated calcium modulator) » PM » Accessory protein downstream of s4m1
- 25. IPA
- 32. Outline • Introduc4on to Interac4on Networks • Basic components of an interac4on network • Types of interac4on networks • Predic4ng Protein‐Protein Interac4on Networks • Methods » Logic and concept • Available Interac4on data • Integrated protein‐protein interac4on databases • Searching for interac4on data • Network Visualiza4on and Analysis tools • Popular visualiza4on tools • Network analysis • Demonstra4on • Predic4on of interac4on (PPI…?) network from microarray (ARACNE) • Visualiza4on and analysis of the predicted network (Cytoscape)
- 33. • Cytoscape • VisANT (Integra4ve Visual Analysis Tool) • Osprey • BioLayout Popular Visualiza-on Tools
- 34. VisANT
- 43. Analysis Tools • Phunkee (Pairing subgraphs Using Network Environment Equivalence – finds similar subnets) • mfinder (mo4f detec4on) • MAVisto (Mo4f Analysis and Visualiza4on tool – explora4on of mo4fs) • GraphMatch (Search for similar sub‐nets) • NeAT (Network Analysis Tools – mo4f finding, node sta4s4cs) • Cfinder (Finds clusters – dense group of nodes) • NetworkBLAST (Compares mul4ple networks to infer complexes & paths)
- 44. Outline • Introduc4on to Interac4on Networks • Basic components of an interac4on network • Types of interac4on networks • Predic4ng Protein‐Protein Interac4on Networks • Methods » Logic and concept • Available Interac4on data • Integrated protein‐protein interac4on databases • Searching for interac4on data • Network Visualiza4on and Analysis tools • Popular visualiza4on tools • Network analysis • Demonstra4on • Predic4on of interac4on (PPI…?) network from microarray (ARACNE) • Visualiza4on and analysis of the predicted network (Cytoscape)
- 45. PPI Predic-on Using Microarray Data • Co‐expression concept • Correla4on Coefficient » SIMoNE (Sta4s4cal Inference for Modular Networks) ‐ R • Mutual Informa4on » Reference Networks » ARACNE (Algorithm for Reconstruc4on of Accurate Cellular Networks) – R, geWorkbench » CLR (Context Likelihood of Relatedness) – R » MRNET (Maximum Relevance/Minimum Redundancy) – R » MONET (Modularized NETwork Learning) ‐ Cytoscape • Bayesian Network
- 46. PPI Predic-on Using Microarray Data • Melanoma metastasis • 83 samples • Affymetrix • GEO • ARACNE • geWorkbench • IP3R1, IP3R2, IP3R3, STIM1, ORAI1
- 58. GML File
- 59. Predicted PPI Network • Could form a complex • Could be func4onally associated • Could be involved in a same metabolic pathway • Could be involved in a specific signal transduc4on path • False posi4ve
- 60. Visualiza-on and Analysis Using Cytoscape • Cytoscape • Opensource • Works in Windows, Linux, Mac • One of the first developed tools • Great number of PLUGINS • Excellent help from community
- 69. Data Visualiza-on, Integra-on, Analysis • Import ARACNE predicted network • Import VisANT retrieved network • Merge all networks • Mo4f finding
- 79. NetCirChro (Networks on Circular Chromosomes ) ‐ Citrate cycle B. sub'lis E. coli S. typhi S. aureus Gram-negative Bacteria Gram-positive Bacteria