Janaina Cruz Pereira1, Samer S Daher1, Kimberley M Zorn2, Matthew Sherwood1, Riccardo Russo3, Alexander L Perryman1,4, Xin Wang1,5, Madeleine J Freundlich6, Sean Ekins2,7, Joel S Freundlich8,9. 1. Department of Pharmacology, Physiology, and Neuroscience, Rutgers University New Jersey Medical School, I-503 185 South Orange Avenue, Newark, NJ, 07103, USA. 2. Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC, 27606, USA. 3. Division of Infectious Disease, Department of Medicine and the Ruy V. Lourenço Center for the Study of Emerging and Re-emerging Pathogens, Rutgers University New Jersey Medical School, I-503 185 South Orange Avenue, Newark, NJ, 07103, USA. 4. Repare Therapeutics,, 7210 Rue Frederick-Banting Suite 100, Montreal, QC, H4S 2A1, Canada. 5. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Stuart Country Day School of the Sacred Heart, 1200 Stuart Road, Princeton, NJ, 08540, USA. 7. Collaborations in Chemistry, Inc. 5616 Hilltop Needmore Road, Fuquay-, Varina, NC, 27526, USA. 8. Department of Pharmacology, Physiology, and Neuroscience, Rutgers University New Jersey Medical School, I-503 185 South Orange Avenue, Newark, NJ, 07103, USA. freundjs@rutgers.edu. 9. Division of Infectious Disease, Department of Medicine and the Ruy V. Lourenço Center for the Study of Emerging and Re-emerging Pathogens, Rutgers University New Jersey Medical School, I-503 185 South Orange Avenue, Newark, NJ, 07103, USA. freundjs@rutgers.edu.
Abstract
PURPOSE: To advance fundamental biological and translational research with the bacterium Neisseria gonorrhoeae through the prediction of novel small molecule growth inhibitors via naïve Bayesian modeling methodology. METHODS: Inspection and curation of data from the publicly available ChEMBL web site for small molecule growth inhibition data of the bacterium Neisseria gonorrhoeae resulted in a training set for the construction of machine learning models. A naïve Bayesian model for bacterial growth inhibition was utilized in a workflow to predict novel antibacterial agents against this bacterium of global health relevance from a commercial library of >105 drug-like small molecules. Follow-up efforts involved empirical assessment of the predictions and validation of the hits. RESULTS: Specifically, two small molecules were found that exhibited promising activity profiles and represent novel chemotypes for agents against N. gonorrrhoeae. CONCLUSIONS: This represents, to the best of our knowledge, the first machine learning approach to successfully predict novel growth inhibitors of this bacterium. To assist the chemical tool and drug discovery fields, we have made our curated training set available as part of the Supplementary Material and the Bayesian model is accessible via the web. Graphical Abstract.
PURPOSE: To advance fundamental biological and translational research with the bacterium Neisseria gonorrhoeae through the prediction of novel small molecule growth inhibitors via naïve Bayesian modeling methodology. METHODS: Inspection and curation of data from the publicly available ChEMBL web site for small molecule growth inhibition data of the bacterium Neisseria gonorrhoeae resulted in a training set for the construction of machine learning models. A naïve Bayesian model for bacterial growth inhibition was utilized in a workflow to predict novel antibacterial agents against this bacterium of global health relevance from a commercial library of >105 drug-like small molecules. Follow-up efforts involved empirical assessment of the predictions and validation of the hits. RESULTS: Specifically, two small molecules were found that exhibited promising activity profiles and represent novel chemotypes for agents against N. gonorrrhoeae. CONCLUSIONS: This represents, to the best of our knowledge, the first machine learning approach to successfully predict novel growth inhibitors of this bacterium. To assist the chemical tool and drug discovery fields, we have made our curated training set available as part of the Supplementary Material and the Bayesian model is accessible via the web. Graphical Abstract.
Entities:
Keywords:
Diversity; Naïve Bayesian classifier; Neisseria gonorrhoeae; machine learning model
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