Context-driven discovery of gene cassettes in mobile integrons using a computational grammar
<p>Abstract</p> <p>Background</p> <p>Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-09-01
|
| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/10/281 |
| _version_ | 1811278620332654592 |
|---|---|
| author | Schaeffer Jaron Partridge Sally R Coiera Enrico Tsafnat Guy Iredell Jon R |
| author_facet | Schaeffer Jaron Partridge Sally R Coiera Enrico Tsafnat Guy Iredell Jon R |
| author_sort | Schaeffer Jaron |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to the discovery of gene cassettes associated with integrons. The discovery and annotation of antibiotic resistance genes in such cassettes is essential for effective monitoring of antibiotic resistance patterns and formulation of public health antibiotic prescription policies.</p> <p>Results</p> <p>We discovered two new putative gene cassettes using the method, from 276 integron features and 978 GenBank sequences. The system achieved <it>κ </it>= 0.972 annotation agreement with an expert gold standard of 300 sequences. In rediscovery experiments, we deleted 789,196 cassette instances over 2030 experiments and correctly relabelled 85.6% (<it>α </it>≥ 95%, <it>E </it>≤ 1%, mean sensitivity = 0.86, specificity = 1, F-score = 0.93), with no false positives.</p> <p>Error analysis demonstrated that for 72,338 missed deletions, two adjacent deleted cassettes were labeled as a single cassette, increasing performance to 94.8% (mean sensitivity = 0.92, specificity = 1, F-score = 0.96).</p> <p>Conclusion</p> <p>Using grammars we were able to represent heuristic background knowledge about large and complex structures in DNA. Importantly, we were also able to use the context embedded in the model to discover new putative antibiotic resistance gene cassettes. The method is complementary to existing automatic annotation systems which operate at the sequence level.</p> |
| first_indexed | 2024-04-13T00:39:06Z |
| format | Article |
| id | doaj.art-96d4d8b15ab945fc84b7d30ffe7e66d4 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-13T00:39:06Z |
| publishDate | 2009-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-96d4d8b15ab945fc84b7d30ffe7e66d42022-12-22T03:10:14ZengBMCBMC Bioinformatics1471-21052009-09-0110128110.1186/1471-2105-10-281Context-driven discovery of gene cassettes in mobile integrons using a computational grammarSchaeffer JaronPartridge Sally RCoiera EnricoTsafnat GuyIredell Jon R<p>Abstract</p> <p>Background</p> <p>Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to the discovery of gene cassettes associated with integrons. The discovery and annotation of antibiotic resistance genes in such cassettes is essential for effective monitoring of antibiotic resistance patterns and formulation of public health antibiotic prescription policies.</p> <p>Results</p> <p>We discovered two new putative gene cassettes using the method, from 276 integron features and 978 GenBank sequences. The system achieved <it>κ </it>= 0.972 annotation agreement with an expert gold standard of 300 sequences. In rediscovery experiments, we deleted 789,196 cassette instances over 2030 experiments and correctly relabelled 85.6% (<it>α </it>≥ 95%, <it>E </it>≤ 1%, mean sensitivity = 0.86, specificity = 1, F-score = 0.93), with no false positives.</p> <p>Error analysis demonstrated that for 72,338 missed deletions, two adjacent deleted cassettes were labeled as a single cassette, increasing performance to 94.8% (mean sensitivity = 0.92, specificity = 1, F-score = 0.96).</p> <p>Conclusion</p> <p>Using grammars we were able to represent heuristic background knowledge about large and complex structures in DNA. Importantly, we were also able to use the context embedded in the model to discover new putative antibiotic resistance gene cassettes. The method is complementary to existing automatic annotation systems which operate at the sequence level.</p>http://www.biomedcentral.com/1471-2105/10/281 |
| spellingShingle | Schaeffer Jaron Partridge Sally R Coiera Enrico Tsafnat Guy Iredell Jon R Context-driven discovery of gene cassettes in mobile integrons using a computational grammar BMC Bioinformatics |
| title | Context-driven discovery of gene cassettes in mobile integrons using a computational grammar |
| title_full | Context-driven discovery of gene cassettes in mobile integrons using a computational grammar |
| title_fullStr | Context-driven discovery of gene cassettes in mobile integrons using a computational grammar |
| title_full_unstemmed | Context-driven discovery of gene cassettes in mobile integrons using a computational grammar |
| title_short | Context-driven discovery of gene cassettes in mobile integrons using a computational grammar |
| title_sort | context driven discovery of gene cassettes in mobile integrons using a computational grammar |
| url | http://www.biomedcentral.com/1471-2105/10/281 |
| work_keys_str_mv | AT schaefferjaron contextdrivendiscoveryofgenecassettesinmobileintegronsusingacomputationalgrammar AT partridgesallyr contextdrivendiscoveryofgenecassettesinmobileintegronsusingacomputationalgrammar AT coieraenrico contextdrivendiscoveryofgenecassettesinmobileintegronsusingacomputationalgrammar AT tsafnatguy contextdrivendiscoveryofgenecassettesinmobileintegronsusingacomputationalgrammar AT iredelljonr contextdrivendiscoveryofgenecassettesinmobileintegronsusingacomputationalgrammar |