Interactive Network Construction Using R and cRytoscape

Paul ShannonInstitute for Systems Biology

August 25th, 2009

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

33 Early Spike Genes

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))

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))

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))

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))

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))

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))

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))

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))

Early Spike Gene Symbols

GO BP for Early Spike Genes

Rendered

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'))

Interpolating Network Edges(HPRD ‘empirical’)

5 Interpolated Edges

Profile of Interpolated Genes: NFKB1 & HMGB1

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 theNF-kappaB-dependent expression of the adhesion molecule VCAM-1.

Reject or Tentatively Accept?

NFKB1 & ATF3: abstract ('7692236'): Cyclic AMP-independent ATF family membersinteract with NF-kappa B and function in the activation of the E-selectinpromoter in response to cytokines….

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 ()

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 ()

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.