SUMMARY: Many online sources of gene interaction networks supply rich visual data regarding gene pathways that can aid in the study of biological processes, disease research and drug discovery. PathGen incorporates data from several sources to create transitive connections that span multiple gene interaction databases. Results are displayed in a comprehensible graphical format, showing gene interaction type and strength, database source and microarray expression data. These features make PathGen a valuable tool for in silico discovery of novel gene interaction pathways, which can be experimentally tested and verified. The usefulness of PathGen interaction analyses was validated using genes connected to the altered facial development related to Down syndrome. AVAILABILITY: http://dna.cs.byu.edu/pathgen. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Further information is available at http://dna.cs.byu.edu/pathgen/PathGenSupplemental.pdf.

The relationship between changes in gene expression and physical characteristics associated with Down syndrome is not well understood. Chromosome 21 genes interact with nonchromosome 21 genes to produce Down syndrome characteristics. This indirect influence, however, is difficult to empirically define due to the number, size, and complexity of the involved gene regulatory networks. This work links chromosome 21 genes to non-chromosome 21 genes known to interact in a Down syndrome phenotype through a reachability analysis of labeled transition graphs extracted from published gene regulatory network databases. The analysis provides new relations in a recently discovered link between a specific gene and Down syndrome phenotype. This type of formal analysis helps scientists direct empirical studies to unravel chromosome 21 gene interactions with the hope for therapeutic intervention.