Meta-Analysis of Nanoparticle Cytotoxicity via Data-Mining the Literature.

Developing predictive modeling frameworks of potential cytotoxicity of engineered nanoparticles is critical for environmental and health risk analysis. The complexity and the heterogeneity of available data on potential risks of nanoparticles, in addition to interdependency of relevant influential attributes makes it challenging to develop a generalization of nanoparticle toxicity behaviour. Lack of systematic approaches to investigate these risks further adds uncertainties and variability to the body of literature and limits generalizability of existing studies. Here, we developed a rigorous approach for assembling published evidence on cytotoxicity of several organic and inorganic nanoparticles and unraveled hidden relationships that were not targeted in the original publications. We used a machine learning approach that employs decision trees together with feature selection algorithms (e.g. Gain ratio) to analyze a set of published nanoparticle cytotoxicity sample data (2896 samples). The specific studies were selected because they specified nanoparticle-, cell- and screening method-related attributes. The resultant decision-tree classifiers are sufficiently simple, accurate and with high prediction power and should be widely applicable to a spectrum of nanoparticle cytotoxicity settings. Among several influential attributes, we show that the cytotoxicity of nanoparticles is primarily predicted from the nanoparticle material chemistry, followed by nanoparticle concentration and size, cell type and nanoparticles cytotoxicity screening indicator. Overall, our study indicates that following rigorous and transparent methodological experimental approaches, in parallel to continuous addition to this dataset developed using our approach will offer higher predictive power and accuracy and uncover hidden relationships. Results obtained in this study helps focus future studies to help in the development of nanoparticles that are safe-by-design.