Frequently, homology is used as a reason to transfer knowledge about function or structure from known to unknown proteins. Although phylogenies are the method of choice when attempting to determine homology, the most frequently used marker is pairwise sequence similarity. Similarity search programs, such as BLAST or PSI-BLAST (Altschul et al. 1997), can efficiently work with enormous data sets while phylogenetic inference and the prerequisite sequence alignments rapidly reach a point where they become unsuitable due to prohibitive calculation costs and loss of resolution. On the other hand, pairwise similarity searches are plagued by false positive matches and problems arising from amino acid composition bias causing, in many cases, the best BLAST hits not to be the closest sequence relatives (Koski & Golding 2001).
Aiming for the best of both worlds, we have implemented a version of the Fruchterman-Reingold graph-layout algorithm (1991). The program takes unaligned fasta format sequences a input, performs all-against-all BLAST searches and displays the pairwise similarities in either 2D or 3D graphs. Contrary to phylogenetic inference methods this approach uses unaligned sequences and works better the more sequences are provided as an increase in number of pairwise similarities better averages out the chance hits that plague standard BLAST comparisons.
Although the application is meant for use with protein sequences, any kind of pairwise similarity data can be displayed (see below: HHSearch results & BLOSUM62).
Altschul S.F., Madden T.L., Schaffer A.A., Zhang J., Miller W., Lipman D.J., (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25:3389-3444
Enright A.J., Ouzounis C.A., (2001) BioLayout - an automatic graph layout algorithm for similarity visualization. Bioinformatics 17:853-854
Fruchterman T.M., Reingold E.M., (1991) Force directed placement, Softw. -Pract. Exp. 21:1129-1164
Koski L.B., Golding G.B., (2001) The closest BLAST hit Is Often Not the Nearest Neighbor, J. Mol. Evol. 52:540-542