Pathogen-Host Omics Data Figure 5. Vaccinia virus, human protein interaction network. A) Triangular nodes represent Vaccinia proteins, round nodes human proteins. Colors represent relative abundance as determined by peptide counts. Grey nodes represent no peptide data, green to yellow to orange to red represent increasing spectral counts in the range of 3 to 543. B) The three interactions, discussed in the text. The host protein (Keratin, type II cytoskeletal 4, UniProt: P19013) and three viral proteins (P11258 - 14 kDa fusion protein, A27L; Q805H7 - Chemokine-binding protein C23/B29; P17362 - Protein C6L). doi:10.1371/journal.pone.0007162.g005 4 in human saliva has been shown to interact with the protein Srr- 1 localized on the surface of Streptococcus agalactiae and to play a critical role in colonization of this bacterial pathogen [50,51]. Little is known about the mechanisms by which poxviruses attach to and enter host cells. No receptor for virion attachment on the host cell surface has been found. Poxvirus infection can occur through interaction with human as well as mice airway epithelia, [52,53] we propose that the protein interactions outlined above may represent some of the initial interactions between host and pathogen. Thus they represent potential therapeutic targets for further investigation. This is the first report describing the interaction of a poxvirus protein with a host Keratin, type II cytoskeletal 4 protein. Example III: Screening for Pathogen Specific Target Proteins. Unequivocal identification of pathogens is important so that adequate counter measures can be taken. Currently over 700 pathogenic and non-pathogenic bacteria have been completely sequenced. The availability of sequence data allows identification of proteins that are unique at different taxonomic levels, thus providing a means to begin to distinguish pathogenic from non-pathogenic species. However, if the initial screening depends on sequence data alone, the list of potential targets for laboratory validation can be relatively long; by supplementing sequence results with experimental data one can prioritize the target list for validation in the laboratory. We used such an approach by computationally screening potential targets using CUPID [54], PRC data and other computational means to produce a list of potential targets. Identifying species-specific proteins can be done with confidence when multiple species and strains have been sequenced as is the case with Bacillus anthracis. The approach relies on the fact that if a gene is conserved over time within multiple strains it gives confidence they will not be lost in the near future and hence are ideal for diagnostic targets. These ‘‘core unique’’ proteins have related sequences in all selected organisms (in this case all available strains of Bacillus anthracis) but not in other related organisms. An initial total of 327 proteins unique to the Bacillus anthracis proteome were identified using the CUPID and UniProtKB version 13.0. (Bacillus anthracis strain Ames isolate Porton, Bacillus anthracis strain Ames ancestor, Bacillus anthracis strain Sterne were compared to twelve other genomes in the Bacillus genus). The two closest relatives of Bacillus anthracis as determined by CUPID are Bacillus thuringiensis and Bacillus cereus. The species most closely related to the selected organism is based on the best BLAST hits of its entire PLoS ONE | www.plosone.org 8 September 2009 | Volume 4 | Issue 9 | e7162