Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules.
BACKGROUND
Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense) that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage.


RESULTS
The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with 'High' reliability scoring), DEREK (accuracy = 72.73% and CCR = 71.44%) and TOPKAT (accuracy = 60.00% and CCR = 61.67%). Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%), the coverage was very low (only 10 out of 77 molecules were predicted reliably).


CONCLUSIONS
Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing.
LABS, Persistent Systems Limited, Pune, Maharashtra, India.|Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Vaishali, Bihar, India.
Konda Leela
KL
Sarath Kumar
LABS, Persistent Systems Limited, Pune, Maharashtra, India.|Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Vaishali, Bihar, India.
Sujit R
SR
Tangadpalliwar
LABS, Persistent Systems Limited, Pune, Maharashtra, India.
Aarti
A
Desai
LABS, Persistent Systems Limited, Pune, Maharashtra, India.
Vivek K
VK
Singh
LABS, Persistent Systems Limited, Pune, Maharashtra, India.
Abhay
A
Jere
D000818:Animals; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008954:Models, Biological; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology