Parikh, Jignesh R.Xia, YuMarto, Jarrod2013-04-052012Parikh, Jignesh R., Yu Xia, and Jarrod A. Marto. 2012. Multi-edge gene set networks reveal novel insights into global relationships between biological themes. PLoS ONE 7(9): e45211.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10498783Curated gene sets from databases such as KEGG Pathway and Gene Ontology are often used to systematically organize lists of genes or proteins derived from high-throughput data. However, the information content inherent to some relationships between the interrogated gene sets, such as pathway crosstalk, is often underutilized. A gene set network, where nodes representing individual gene sets such as KEGG pathways are connected to indicate a functional dependency, is well suited to visualize and analyze global gene set relationships. Here we introduce a novel gene set network construction algorithm that integrates gene lists derived from high-throughput experiments with curated gene sets to construct co-enrichment gene set networks. Along with previously described co-membership and linkage algorithms, we apply the co-enrichment algorithm to eight gene set collections to construct integrated multi-evidence gene set networks with multiple edge types connecting gene sets. We demonstrate the utility of approach through examples of novel gene set networks such as the chromosome map co-differential expression gene set network. A total of twenty-four gene set networks are exposed via a web tool called MetaNet, where context-specific multi-edge gene set networks are constructed from enriched gene sets within user-defined gene lists. MetaNet is freely available at http://blaispathways.dfci.harvard.edu/metanet/.en-USBiologyComputational BiologyGenomicsGenome Analysis ToolsGenetic NetworksBiological Data ManagementMicroarraysRegulatory NetworksSignaling NetworksMolecular Cell BiologySignal TransductionSignaling PathwaysGene ExpressionComputer ScienceAlgorithmsComputer ApplicationsWeb-Based ApplicationsJournal Article2013-04-0510.1371/journal.pone.0045211