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Similar to Eccmid 2015 Mykrobe Predictor - A desktop application identifying species and antibiotic resistance from S. aureus and M. tuberculosis raw genome sequence data.
Similar to Eccmid 2015 Mykrobe Predictor - A desktop application identifying species and antibiotic resistance from S. aureus and M. tuberculosis raw genome sequence data. (20)
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Eccmid 2015 Mykrobe Predictor - A desktop application identifying species and antibiotic resistance from S. aureus and M. tuberculosis raw genome sequence data.
- 1. Wellcome Trust Centre for Human Genetics Mykrobe predictor A desktop application identifying species and antibiotic resistance from S. aureus and M. tuberculosis raw genome sequence data. Phelim Bradley phelimb@well.ox.ac.uk Zamin Iqbal zam@well.ox.ac.uk
- 2. How can we make clinical genomics a practical reality? Mykrobe predictor is clinical grade software to enable sequencing data to be used to identify species and test for drug susceptibility. Mykrobe predictor is: • Quick • Usable by non informatics-experts • Scalable • As accurate as comparable drug susceptibility tests.
- 3. Mykrobe replaces post culture DST with whole genome sequencing + software analysis. Mykrobe predictor fits into clinical workflow.
- 4. Drag and drop demo
- 5. Drag and drop demo
- 6. Drag and drop demo
- 7. Drag and drop demo
- 8. Drag and drop demo
- 9. Drag and drop demo
- 10. Drag and drop demo
- 11. Drag and drop demo
- 12. Future advances may decrease required culture times Can we also be robust to decreased culture times? SequencingCulture Mykrobe
- 13. Future advances may decrease required culture times Can we also be robust to decreased culture times? SequencingCulture Mykrobe
- 14. Mykrobe has been trained and tested on 1000s of samples • 987 S. aureus and 3529 M. tuberculosis samples (Illumina HiSeq) S. aureus: • Resistance predictions for 12 drugs: Penicillin, Erythromycin, Ciprofloxacin, Methicillin, Fusidic Acid, Tetracycline, Rifampicin, Gentamycin, Mupirocin and Vancomycin. • Gold-standard phenotype = a consensus of antibiotic BSAC disc, Phoenix™ and Etest. M. tuberculosis: • Resistance predictions for 10 1st and 2nd line drugs: Isoniazid, Rifampicin, Ethambutol, Streptomycin, Amoxicillin, Ofloxacin, Amikacin, Capreomycin, Kanamycin. • Gold-standard phenotype = proportion method via Löwenstein- Jensen slope-based testing.
- 15. Results – toy example Sample Predict Truth 1 R R 2 R R 3 R R 4 S R 5 S R 6 S R 7 S R 8 S R 9 S R 10 S R 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples VME = Very major error (incorrect S prediction) (Correct R predictions)
- 16. 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples Results – toy example Sample Predict Truth 1 R R 2 R R 3 R R 4 R R 5 R R 6 R R 7 R R 8 S R 9 S R 10 S R VME = Very major error (incorrect S prediction) TP (Correct R predictions)
- 17. 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples Results – toy example Sample Predict Truth 1 R R 2 R R 3 R R 4 R R 5 R R 6 R R 7 R R 8 R R 9 R R 10 R R TP (Correct R predictions)
- 18. 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples Results – toy example Sample Predict Truth 11 S S 12 S S 13 S S 14 R S 15 R S 16 R S 17 R S 18 R S 19 R S 20 R S 0 1 2 3 4 5 6 7 8 9 10 drug SusceptibleSamples TN ME = Major error (incorrect R prediction)
- 19. 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples Results – toy example Sample Predict Truth 11 S S 12 S S 13 S S 14 S S 15 S S 16 S S 17 S S 18 R S 19 R S 20 R S TN ME = Major error (incorrect R prediction) 0 1 2 3 4 5 6 7 8 9 10 drug SusceptibleSamples
- 20. 0 1 2 3 4 5 6 7 8 9 10 drug SusceptibleSamples 0 1 2 3 4 5 6 7 8 9 10 drug ResistantSamples Results – toy example Sample Predict Truth 11 S S 12 S S 13 S S 14 S S 15 S S 16 S S 17 S S 18 S S 19 S S 20 S S TN
- 21. Mykrobe predictor is as sensitive and specific as Disc and Phoenix for S. aureus DST . • We achieved an overall 0.7% VME rate and 0.5% ME rate across all antibiotics in S. aureus. VME – missed R predictions ME – missed S predictions
- 22. Comparison to comparable MTB DST • Gold standard resistance predictions are slow. • Faster options: • PCR based test (e.g. CEPHEID GeneXpert) • Limited scope (Only RIF predictions) • Line probe assay (e.g. HAIN MTBDR) • Static, difficult to update targets. • Sequencing (e.g. Mykrobe predictor) • Flexible, updatable panel. • Single, quantitative test
- 23. Ability to detect minor populations has potential clinical benefit. • Detect coagulase-negative staphylococci • Detect atypical mycobacteria • Minor calls improve VME in 2nd line tuberculosis drugs.
- 24. Sequence data has additional benefits Sequencing based solutions will • Help us better understand within patient diversity • Fit in with a global surveillance system
- 25. The Future: A sequencer in your USB stick? Silicon Revolution (Moore’s Law) Sequencing Technology
- 26. The Future: A sequencer in your USB stick? PEN R ERY R CIP R METH R FUS S CLIN R TET S RIF S GEN R MUP S TRIM R VAN S
- 27. Mykrobe is ready for field trips… Tablet Smart Phone Raspberry Pi Model B - CHEAP!!
- 28. • Mykrobe predictor is ready for : • Windows • Mac • Linux • Basespace (submitted) • Will be tested in 3 UK hospitals in 2015 Mykrobe predictor Try it out! - you can download it now. mykrobe.com
- 29. Acknowledgments PI - Zam Iqbal • Simon Heys, Bill Huang • Claire Gordon, Tim Walker, Tim Peto, Sarah Walker, Louise Pankhurst, Antonina Votintseva, Derrick Crook • Mariateresa deCesare, David Buck, Gil McVean. • Stefan Niemann, E Grace Smith, Nazir Ismail, Roland Diel, Shaheed Omar
- 30. phelimb@well.ox.ac.uk zam@well.ox.ac.uk @phelimb @ZaminIqbal Thanks for listening. http://mykrobe.com
- 32. Mykrobe replaces post culture DST with whole genome sequencing + software analysis. Mykrobe predictor fits into clinical workflow. M. tuberculosis
- 33. Mykrobe replaces post culture DST with whole genome sequencing + software analysis. Mykrobe predictor fits into clinical workflow. S. aureus
- 34. Future advances may decrease required culture times Can we also make it robust to decreased culture times? S. aureus
- 35. M. Predictor can accurately determine target species. • Speciation was tuned to be as sensitive and specific to target species. • Sensitivity and specificity to detect S. Aureus -100%, 98.5% • Sensitivity and specificity to detect MTBC - 100%,100%
Editor's Notes
- drug susceptibility predictions are then displayed in an intuitive manner. You can view the predictions split by S and R or by class
- Or by drug class
- Virulence prediction – extensible.
- You can use your own catalogue.
- Species + contamination check
- Stop missing any mising R samples
- Illumina basespace (submitted) Available on windows mac linux.
- (automation, reproducibility, regulation) ----- Meeting Notes (22/04/15 14:42) ----- Mykrobe predictor fits into the clincal workflow post cuture and can replace the species idetification, contamination check and susceptibility predcitions. Mykrobe can be automatisted, is reproducable.