Naïve Bayesian Models for Vero Cell Cytotoxicity
To advance translational research of potential therapeutic small molecules against infectious microbes, the compounds must display a relative lack of mammalian cell cytotoxicity. Vero cell cytotoxicity (CC50) is a common initial assay for this metric. We explored the development of naïve Bayesian models that can enhance the probability of identifying non-cytotoxic compounds.
Vero cell cytotoxicity assays were identified in PubChem, reformatted, and curated to create a training set with 8741 unique small molecules. These data were used to develop Bayesian classifiers, which were assessed with internal cross-validation, external tests with a set of 193 compounds from our laboratory, and independent validation with an additional diverse set of 1609 unique compounds from PubChem.
Evaluation with independent, external test and validation sets indicated that cytotoxicity Bayesian models constructed with the ECFP_6 descriptor were more accurate than those that used FCFP_6 fingerprints. The best cytotoxicity Bayesian model displayed predictive power in external evaluations, according to conventional and chance-corrected statistics, as well as enrichment factors.
The results from external tests demonstrate that our novel cytotoxicity Bayesian model displays sufficient predictive power to help guide translational research. To assist the chemical tool and drug discovery communities, our curated training set is being distributed as part of the Supplementary Material.
Key WordsBayesian model machine learning predicting mammalian cytotoxicity translational research vero cell CC50
Absorption, metabolism, distribution, excretion and toxicity
Assay Identification number on PubChem BioAssay
Extended class fingerprints of maximum diameter 6
Molecular function class fingerprints of maximum diameter 6
Negative predictive value (filtering rate)
Positive predictive value (hit rate)
Quantitative Structure-Activity Relationships
Simplified molecular-input line-entry system
- Vero CC50
Vero cell (African green monkey kidney cell) 50% cytotoxicity value
Compliance with Ethical Standards
Conflicts of Interest
S.E. is the Founder and CEO of Collaborations Pharmaceuticals Inc.