  The evolutionary pressures that underlie the large-scale functional
organization of the genome are not well understood in eukaryotes. Recent
evidence suggests that functionally similar genes may colocalize (cluster) in
the eukaryotic genome, suggesting the role of chromatin-level gene regulation
in shaping the physical distribution of coordinated genes. However, few of the
bioinformatic tools currently available allow for a systematic study of gene
colocalization across several, evolutionarily distant species. Kerfuffle is a
web tool designed to help discover, visualize, and quantify the physical
organization of genomes by identifying significant gene colocalization and
conservation across the assembled genomes of available species (currently up to
47, from humans to worms). Kerfuffle only requires the user to specify a list
of human genes and the names of other species of interest. Without further
input from the user, the software queries the e!Ensembl BioMart server to
obtain positional information and discovers homology relations in all genes and
species specified. Using this information, Kerfuffle performs a multi-species
clustering analysis, presents downloadable lists of clustered genes, performs
Monte Carlo statistical significance calculations, estimates how conserved gene
clusters are across species, plots histograms and interactive graphs, allows
users to save their queries, and generates a downloadable visualization of the
clusters using the Circos software. These analyses may be used to further
explore the functional roles of gene clusters by interrogating the enriched
molecular pathways associated with each cluster.
