Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi
<p>Abstract</p> <p>Background</p> <p><it>Wolbachia </it>(<it>w</it>Bm) is an obligate endosymbiotic bacterium of <it>Brugia malayi</it>, a parasitic filarial nematode of humans and one of the causative agents of lymphatic filariasis....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-11-01
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| Series: | BMC Microbiology |
| Online Access: | http://www.biomedcentral.com/1471-2180/9/243 |
| _version_ | 1818806180221288448 |
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| author | Carlow Clotilde KS Foster Jeremy M Davis Paul J Holman Alexander G Kumar Sanjay |
| author_facet | Carlow Clotilde KS Foster Jeremy M Davis Paul J Holman Alexander G Kumar Sanjay |
| author_sort | Carlow Clotilde KS |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Wolbachia </it>(<it>w</it>Bm) is an obligate endosymbiotic bacterium of <it>Brugia malayi</it>, a parasitic filarial nematode of humans and one of the causative agents of lymphatic filariasis. There is a pressing need for new drugs against filarial parasites, such as <it>B. malayi</it>. As <it>w</it>Bm is required for <it>B. malayi </it>development and fertility, targeting <it>w</it>Bm is a promising approach. However, the lifecycle of neither <it>B. malayi </it>nor <it>w</it>Bm can be maintained <it>in vitro</it>. To facilitate selection of potential drug targets we computationally ranked the <it>w</it>Bm genome based on confidence that a particular gene is essential for the survival of the bacterium.</p> <p>Results</p> <p><it>w</it>Bm protein sequences were aligned using BLAST to the Database of Essential Genes (DEG) version 5.2, a collection of 5,260 experimentally identified essential genes in 15 bacterial strains. A confidence score, the Multiple Hit Score (MHS), was developed to predict each <it>w</it>Bm gene's essentiality based on the top alignments to essential genes in each bacterial strain. This method was validated using a jackknife methodology to test the ability to recover known essential genes in a control genome. A second estimation of essentiality, the Gene Conservation Score (GCS), was calculated on the basis of phyletic conservation of genes across <it>Wolbachia's </it>parent order <it>Rickettsiales</it>. Clusters of orthologous genes were predicted within the 27 currently available complete genomes. Druggability of <it>w</it>Bm proteins was predicted by alignment to a database of protein targets of known compounds.</p> <p>Conclusion</p> <p>Ranking <it>w</it>Bm genes by either MHS or GCS predicts and prioritizes potentially essential genes. Comparison of the MHS to GCS produces quadrants representing four types of predictions: those with high confidence of essentiality by both methods (245 genes), those highly conserved across <it>Rickettsiales </it>(299 genes), those similar to distant essential genes (8 genes), and those with low confidence of essentiality (253 genes). These data facilitate selection of <it>w</it>Bm genes for entry into drug design pipelines.</p> |
| first_indexed | 2024-12-18T19:05:40Z |
| format | Article |
| id | doaj.art-16496be053ca40e6926f1ccaf1ae0849 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-18T19:05:40Z |
| publishDate | 2009-11-01 |
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| spelling | doaj.art-16496be053ca40e6926f1ccaf1ae08492022-12-21T20:56:25ZengBMCBMC Microbiology1471-21802009-11-019124310.1186/1471-2180-9-243Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayiCarlow Clotilde KSFoster Jeremy MDavis Paul JHolman Alexander GKumar Sanjay<p>Abstract</p> <p>Background</p> <p><it>Wolbachia </it>(<it>w</it>Bm) is an obligate endosymbiotic bacterium of <it>Brugia malayi</it>, a parasitic filarial nematode of humans and one of the causative agents of lymphatic filariasis. There is a pressing need for new drugs against filarial parasites, such as <it>B. malayi</it>. As <it>w</it>Bm is required for <it>B. malayi </it>development and fertility, targeting <it>w</it>Bm is a promising approach. However, the lifecycle of neither <it>B. malayi </it>nor <it>w</it>Bm can be maintained <it>in vitro</it>. To facilitate selection of potential drug targets we computationally ranked the <it>w</it>Bm genome based on confidence that a particular gene is essential for the survival of the bacterium.</p> <p>Results</p> <p><it>w</it>Bm protein sequences were aligned using BLAST to the Database of Essential Genes (DEG) version 5.2, a collection of 5,260 experimentally identified essential genes in 15 bacterial strains. A confidence score, the Multiple Hit Score (MHS), was developed to predict each <it>w</it>Bm gene's essentiality based on the top alignments to essential genes in each bacterial strain. This method was validated using a jackknife methodology to test the ability to recover known essential genes in a control genome. A second estimation of essentiality, the Gene Conservation Score (GCS), was calculated on the basis of phyletic conservation of genes across <it>Wolbachia's </it>parent order <it>Rickettsiales</it>. Clusters of orthologous genes were predicted within the 27 currently available complete genomes. Druggability of <it>w</it>Bm proteins was predicted by alignment to a database of protein targets of known compounds.</p> <p>Conclusion</p> <p>Ranking <it>w</it>Bm genes by either MHS or GCS predicts and prioritizes potentially essential genes. Comparison of the MHS to GCS produces quadrants representing four types of predictions: those with high confidence of essentiality by both methods (245 genes), those highly conserved across <it>Rickettsiales </it>(299 genes), those similar to distant essential genes (8 genes), and those with low confidence of essentiality (253 genes). These data facilitate selection of <it>w</it>Bm genes for entry into drug design pipelines.</p>http://www.biomedcentral.com/1471-2180/9/243 |
| spellingShingle | Carlow Clotilde KS Foster Jeremy M Davis Paul J Holman Alexander G Kumar Sanjay Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi BMC Microbiology |
| title | Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi |
| title_full | Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi |
| title_fullStr | Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi |
| title_full_unstemmed | Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi |
| title_short | Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi |
| title_sort | computational prediction of essential genes in an unculturable endosymbiotic bacterium wolbachia of brugia malayi |
| url | http://www.biomedcentral.com/1471-2180/9/243 |
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