title: Multi-edge gene set networks reveal novel insights into global relationships between biological themes.
abstract: Curated 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/.
authors.affiliation: Bioinformatics Program, Boston University, Boston, Massachusetts, USA.
authors.forename: Jignesh R
authors.initials: JR
authors.lastname: Parikh
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
mesh_terms: D000465:Algorithms; D002874:Chromosome Mapping; D030541:Databases, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D020407:Internet; D012984:Software