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Interactive Network Construction Using R and cRytoscape

Interactive Network Construction Using R and cRytoscape. Paul Shannon Institute for Systems Biology August 25 th , 2009. Interactive Construction: begin, add, reduce. Your experimental d ata Add annotation Calculate functional enrichment

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Interactive Network Construction Using R and cRytoscape

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  1. Interactive Network Construction Using R and cRytoscape Paul Shannon Institute for Systems Biology August 25th, 2009

  2. Interactive Construction: begin, add, reduce • Your experimental data • Add annotation • Calculate functional enrichment • Connect nodes (by function, known interactions, pathway membership) • Eliminate uninteresting edges and nodes • Design the next experiment

  3. 33 Early Spike Genes

  4. Bioconductor Graph + Reworked Cytoscape 1.1: cRytoscape • > g = new ('graphNEL', edgemode='directed’) • > nodeDataDefaults (g, ’geneSymbol') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', ’geneSymbol') = “KLF3” • > nodeLabel (g, ’geneSymbol'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘geneSymbol’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  5. cRytoscape Commands • > nodeDataDefaults (g, ’geneSymbol') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', ’geneSymbol') = “KLF3” • > nodeLabel (g, ’geneSymbol'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘geneSymbol’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  6. cRytoscape Commands • > nodeDataDefaults (g, ’geneSymbol') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', ’geneSymbol') = “KLF3” • > nodeLabel (g, ’geneSymbol'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘geneSymbol’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  7. cRytoscape Commands • > nodeDataDefaults (g, ’geneSymbol') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', ’geneSymbol') = “KLF3” • > nodeLabel (g, ’geneSymbol'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘geneSymbol’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  8. cRytoscape Commands • > nodeDataDefaults (g, ’geneSymbol') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', ’geneSymbol') = “KLF3” • > nodeLabel (g, ’geneSymbol'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘geneSymbol’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  9. cRytoscape Commands • > nodeDataDefaults (g, 'label') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', 'label') = “KLF3” • > nodeLabel (g, 'label'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘label’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  10. cRytoscape Commands • > nodeDataDefaults (g, 'label') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', 'label') = “KLF3” • > nodeLabel (g, 'label'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘label’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  11. cRytoscape Commands • > nodeDataDefaults (g, 'label') = '’ • > g = addNode (‘51724’, g) • > nodeData (g, '51274', 'label') = “KLF3” • > nodeLabel (g, 'label'); render () • > broadcast (c (‘crytoscape.cmd’, ‘vizrule’, ‘nodeLabel’, • ‘lookup’, ‘label’)) • > nodeFontSize (20); render () • > broadcast (c (‘crytoscape.cmd’, "nodeFontSize", 20))

  12. Early Spike Gene Symbols

  13. GO BP for Early Spike Genes

  14. Rendered

  15. An aside: rules for node color & size nodeColor (g.go, 'score', c ('below:white', '0:white', '200:red', 'above:blue')); nodeSize (g.go, 'count', c ('below:30', '1:30', '10:100', 'above:120'))

  16. Interpolating Network Edges(HPRD ‘empirical’)

  17. 5 Interpolated Edges

  18. Profile of Interpolated Genes: NFKB1 & HMGB1

  19. Reject or Tentatively Accept? HMGB1 & FOXC1: abstract ('11748221’): HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences … [has] the ability to bind DNA nonspecifically and to interact with various proteins … transcriptional activators, repressors, co-repressors HMGB1 & NFKB1: abstract ('12604365'): HMGB1 interacts differentially with members of the Rel family of transcription factors ... enhances DNA binding by p65/p50 and p50/p50, but reduces binding by p65/p65 ... Functionally, HMGB1 is required for the NF-kappaB-dependent expression of the adhesion molecule VCAM-1.

  20. Reject or Tentatively Accept? NFKB1 & ATF3: abstract ('7692236'): Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines….

  21. A ‘Little Language’ for Network Visualization from R defaultEdgeStyle (graph, style) defaultNodeBorderColor (graph, color) defaultNodeBorderStyle (graph, style) defaultNodeColor (graph, color) defaultNodeShape (graph, shape) defaultNodeSize (graph, size) defaultSourceArrow (graph, arrow) defaultTargetArrow (graph, arrow) destroy () eda (graph, edge.attribute.name) eda.names (graph) edgeColor (graph, edgeAttributeName, keyValuePairs) edgeColorDiscrete (graph, edgeAttributeName, keyValuePairs) edgeStyle (graph, edgeAttributeName, keyValuePairs) format.long.label (labelString) hide () invert ()

  22. A ‘Little Language’ cont. layout () noa (graph, node.attribute.name) noa.names (graph) nodeBorderColor (graph, nodeAttributeName, keyValuePairs) nodeBorderStyle (graph, nodeAttributeName, keyValuePairs) nodeColor (graph, nodeAttributeName, keyValuePairs) nodeColorDiscrete (graph, nodeAttributeName, keyValuePairs) nodeFontSize (newSize) nodeLabel (graph, nodeAttributeName) nodeShape (graph, nodeAttributeName, keyValuePairs) nodeSize (graph, nodeAttributeName, keyValuePairs) render () select (node.names) sourceArrow (graph, edgeAttributeName, keyValuePairs) targetArrow (graph, edgeAttributeName, keyValuePairs) unhide ()

  23. Conclusions • The interpretation of experimental data is inherently exploratory. • A huge amount of annotation, interaction and pathway information is available, some of it useful in that exploration. • Point-and-click analysis tools are good, but … • Exploration via scripting can sometimes take you further • R and bioconductor offer scripting and many data packages • cRytoscape adds a network visualiztion tool to R • Not yet ready for release, but if anyone is interested, contact me.

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