Phydbac2: improved inference of gene function using interactive phylogenomic profiling and chromosomal location analysis

Phydbac (phylogenomic display of bacterial genes) implemented a method of phylogenomic profiling using a distance measure based on normalized BLAST scores. This method was able to increase the predictive power of phylogenomic profiling by about 25% when compared to the classical approach based on Hamming distances. Here we present a major extension of Phydbac (named here Phydbac2), that extends both the concept and the functionality of the original web-service. While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships. Moreover, all presently available (January 2004) fully sequenced bacterial genomes and those of three lower eukaryotes are now included in the profiling process, thus increasing the initial number of reference genomes (71 in Phydbac) to 150 in Phydbac2. Using the KEGG metabolic pathway database as a benchmark, we show that the predictive power of Phydbac2 is improved by 27% over the previous version. This gain is accounted for on one hand, by the increased number of reference genomes (11%) and on the other hand, as a result of including chromosomal proximity into the distance measure (16%). The expanded functionality of Phydbac2 now allows the user to query more than 50 different genomes, including at least one member of each major bacterial group, most major pathogens and potential bio-terrorism agents. The search for co-evolving genes based on consensus profiles from multiple organisms, the display of Phydbac2 profiles side by side with COG information, the inclusion of KEGG metabolic pathway maps the production of chromosomal proximity maps, and the possibility of collecting and processing results from different Phydbac queries in a common shopping cart are the main new features of Phydbac2. The Phydbac2 web server is available at http://igs-server.cnrs-mrs.fr/phydbac/.

[1]  Jean-Michel Claverie,et al.  Phydbac (phylogenomic display of bacterial genes): an interactive resource for the annotation of bacterial genomes , 2003, Nucleic Acids Res..

[2]  Jean-Michel Claverie,et al.  Annotation of bacterial genomes using improved phylogenomic profiles , 2003, ISMB.

[3]  Michael Y. Galperin,et al.  The COG database: new developments in phylogenetic classification of proteins from complete genomes , 2001, Nucleic Acids Res..

[4]  D. Eisenberg,et al.  Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Anton J. Enright,et al.  Functional associations of proteins in entire genomes by means of exhaustive detection of gene fusions , 2001, Genome Biology.

[6]  Michael Y. Galperin,et al.  Who's your neighbor? New computational approaches for functional genomics , 2000, Nature Biotechnology.

[7]  E. Marcotte,et al.  Computational genetics: finding protein function by nonhomology methods. , 2000, Current opinion in structural biology.

[8]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[9]  Christian von Mering,et al.  STRING: a database of predicted functional associations between proteins , 2003, Nucleic Acids Res..

[10]  B. Snel,et al.  Conservation of gene order: a fingerprint of proteins that physically interact. , 1998, Trends in biochemical sciences.

[11]  Jean-Michel Claverie,et al.  FusionDB: a database for in-depth analysis of prokaryotic gene fusion events , 2004, Nucleic Acids Res..