Limbu, S.; Dakshanamurthy, S. Predicting Dose-Dependent Carcinogenicity of Chemical Mixtures Using a Novel Hybrid Neural Network Framework and Mathematical Approach. Toxics2023, 11, 605.
Limbu, S.; Dakshanamurthy, S. Predicting Dose-Dependent Carcinogenicity of Chemical Mixtures Using a Novel Hybrid Neural Network Framework and Mathematical Approach. Toxics 2023, 11, 605.
Limbu, S.; Dakshanamurthy, S. Predicting Dose-Dependent Carcinogenicity of Chemical Mixtures Using a Novel Hybrid Neural Network Framework and Mathematical Approach. Toxics2023, 11, 605.
Limbu, S.; Dakshanamurthy, S. Predicting Dose-Dependent Carcinogenicity of Chemical Mixtures Using a Novel Hybrid Neural Network Framework and Mathematical Approach. Toxics 2023, 11, 605.
Abstract
This study addresses the challenge of assessing the carcinogenic potential of hazardous chemical mixtures, such as PFAS, which are known to contribute significantly to cancer development. Here, we propose a novel framework called HNNMixCancer that utilizes a Hybrid Neural Network (HNN) integrated into a machine-learning framework. This framework incorporates a mathematical model to simulate chemical mixtures and enables the creation of classification models for binary and multiclass classification and regression. Through extensive experimentation, we demonstrate that our HNN model outperforms other methodologies, including Random Forest, Bootstrap Aggregating, Adaptive Boosting, Support Vector Regressor, Gradient Boosting, Kernel Ridge, Decision Tree with AdaBoost, and KNeighbors, achieving a superior accuracy of 92.7% in binary classification. To address the limited availability of experimental data and enrich the training data, we generate an assumption-based virtual library of chemical mixtures using a known carcinogenic and non-carcinogenic single chemical for all the classification models. Remarkably, in this case, all methods achieve accuracies exceeding 98% for binary classification. In external validation tests, our HNN method achieves the highest accuracy of 80.5%. Furthermore, in multiclass classification, the HNN demonstrates an overall accuracy of 96.3%, outperforming RF, Bagging, and AdaBoost, which achieved 91.4%, 91.7%, and 80.2%, respectively. In regression models, HNN, RF, SVR, GB, KR, DT with AdaBoost, and KN achieve average R2 values of 0.96, 0.90, 0.77, 0.94, 0.96, 0.96, and 0.97, respectively, showcasing their effectiveness in predicting the concentration at which a chemical mixture becomes carcinogenic. Our method exhibits exceptional predictive power in prioritizing carcinogenic chemical mixtures, even when relying on assumption-based mixtures. This capability is particularly valuable for toxicology studies that lack experimental data on the carcinogenicity and toxicity of chemical mixtures. To our knowledge, this study introduces the first method for predicting the carcinogenic potential of chemical mixtures. The HNNMixCancer framework offers a novel alternative for dose-dependent carcinogen prediction. Ongoing efforts involve implementing the HNN method to predict mixture toxicity and expanding the application of HNNMixCancer to include multi-mixtures.
Environmental and Earth Sciences, Environmental Science
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
