The availability of complete genome sequence information for diverse organisms 
including model genetic organisms has ushered in a new era of protein sequence 
comparisons making it possible to search for commonalities among entire 
proteomes using the Basic Local Alignment Search Tool (BLAST). Although the 
identification and analysis of proteins shared by humans and model organisms has 
proven an invaluable tool to understanding gene function, the sets of proteins 
unique to a given model organism's proteome have remained largely unexplored. We 
have constructed a searchable database that allows biologists to identify 
proteins unique to a given proteome. The Negative Proteome Database (NPD) is 
populated with pair-wise protein sequence comparisons between each of the 
following proteomes: Homo sapiens, Mus musculus, Drosophila melanogaster, 
Caenorhabditis elegans, Saccharomyces cerevisiae, Dictyostelium discoideum, 
Chlamydomonus reinhardti, Escherichia coli K12, Arabidopsis thaliana and 
Methanoscarcina acetivorans. Our analysis of negative proteome datasets using 
the NPD has thus far revealed 107 proteins in humans that may be involved in 
motile cilia function, 1628 potential pesticide target proteins in flies, 659 
proteins shared by flies and humans that are not represented in the less 
neurologically complex worm proteome, and 180 nuclear encoded human disease 
associated proteins that are absent from the fly proteome. The NPD is the only 
online resource where users can quickly perform complex negative and positive 
comparisons of model organism proteomes. We anticipate that the NPD and the 
adaptable algorithm which can readily be used to duplicate this analysis on 
custom sets of proteomes will be an invaluable tool in the investigation of 
organism specific protein sets.