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Open Access Highly Accessed Research article

Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes

Maria A Doyle13, Robin B Gasser2*, Ben J Woodcroft1, Ross S Hall2 and Stuart A Ralph1*

Author Affiliations

1 Department of Biochemistry & Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, 3010, Australia

2 Department of Veterinary Science, The University of Melbourne, 250 Princes Highway, Werribee, Victoria, 3030, Australia

3 Current address: Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne Victoria, 3002, Australia

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BMC Genomics 2010, 11:222  doi:10.1186/1471-2164-11-222

Published: 3 April 2010

Additional files

Additional file 1:

Numbers of genes in orthology analysis.doc. This file shows the numbers of genes meeting each of the criteria in our orthology comparisons of essentiality.

Format: DOC Size: 38KB Download file

This file can be viewed with: Microsoft Word Viewer

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Additional file 2:

Fisher's exact test results for orthology analysis.xls. This file contains the results for Fisher's exact test applied to comparisons of essentiality for the model organisms.

Format: XLS Size: 29KB Download file

This file can be viewed with: Microsoft Excel Viewer

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Additional file 3:

Prioritized list of drug targets for A. caninum and H. contortus.xls. The genes in this list are the C. elegans predicted orthologues of the A. caninum and H. contortus ESTs, as identified in the present study. Genes that correspond to validated anthelmintic drug targets are shown in bold. All the genes in this list are predicted enzymes (by GO term) and have a lethal RNAi phenotype in C. elegans. Targets were first prioritized by the essentiality weighting assigned from the present study, then by network connectivity score. "Present in mammals" is defined by having an orthologue in one or more of the mammalian species in the OrthoMCL 2.0 dataset (human, rat, mouse). Essential orthologue in yeast, drosophila or mouse: ✓ = orthologue (with no paralogues) associated with a lethal phenotype, ✘ = orthologue (with no paralogues) that had only non-lethal phenotypes recorded, ? = orthologue (with no paralogues) but no phenotype information was available. Presence of paralogues in C. elegans was determined from the OrthoMCL grouping. Presence of paralogues in A. caninum and H. contortus was determined as described in Materials and methods. The network connectivity score is the sum of all interaction scores (log-likelihood scores) for the gene in the Wormnet core network [37].

Format: XLS Size: 282KB Download file

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Additional file 4:

Phylogenetic trees of nematode and OrthoMCL clusters. This file contains phylogenetic trees of illustrative gene clusters that include ESTs from parasitic nematodes.

Format: PDF Size: 217KB Download file

This file can be viewed with: Adobe Acrobat Reader

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Additional file 5:

Essential phenotypes for C. elegans and M. musculus.doc. This file contains the phenotype descriptions for the C. elegans and M. musculus genes that were classed as essential genes in the current analysis.

Format: DOC Size: 21KB Download file

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