Table S1 - A Comparative Chemogenomics Strategy to Predict Potential Drug Targets in the Metazoan Pathogen, Schistosoma mansoni

This table shows the output and manual curation of potential S. mansoni drug targets generated by comparative genomics with Caenorhabditis elegans and Drosophila melanogaster. The table comprises 7 worksheets each with a different level of information for the respective sequence lists. Leftmost in the table, the first worksheet contains the 72 sequences generated from the two separate electronic workflows utilizing the genome comparison software, Genlight. Each worksheet thereafter represents a subsequent manual curation step involving the removal of sequences (i) that are redundant (remaining 68 non-redundant entries), (ii) that are not confirmed as orthologs by reciprocal blastp searches with both Wormbase and Flybase (remaining 65 confirmed orthologs), (iii) for which targeted gene disruption of the appropriate ortholog does not yield a deleterious phenotype as declared in both Wormbase and Flybase (remaining 58 confirmed phenotypes), (iv) that are not expressed in the relevant developmental stages of the parasite infecting humans (remaining 57 expressed in the relevant life stage; for an explanation of how this was performed see below), (v) that are not druggable as indicated by manual mining of the biological and literature databases available on the internet (remaining 35 druggable targets), and (vi) for which homologous proteins with 3D structural information (including co-crystallized ligands) was not found (remaining 18 proteins with both a 3D structure and co-crystallized ligand). To determine in which developmental stage a putative protein is expressed, the following procedure was performed. In the S. mansoni genome browser [68], the sequence name (e.g., Smp_000040) is imputed into the text field, ��landmark or region��. On the returned search page, the graphic produced by the latest GeneDB working model and displaying the organization of the gene is clicked to reveal a variety of information, including exon/intron junctions, physicochemical characteristics of the putative protein and gene ontology. Activating the hyperlink ��DNA�� reveals the unspliced DNA, spliced DNA and amino acid sequences. Next, a blastn search at NCBI of the spliced sequence is performed via the hyperlink ��Send to BLAST at NCBI��. The analysis is constrained using the search set ��non-human, non-mouse ESTs (EST_others)��, the organism ID number of 6183 for S. mansoni (taxid:6183) and the program selection set to ��somewhat similar sequences��. On the EST list returned, each accession is scrutinized for its life-stage origin by activating the relevant link. The lowest maximum score accepted for consideration was 250. Lower scores tended to be too short to be reliably ascribed to the gene under study. (0.26 MB XLS)