Applying network analysis and Nebula (neighbor-edges based and unbiased leverage algorithm) to ToxCast data

Background: ToxCast data have been used to develop models for predicting in vivo toxicity. To predict the in vivo toxicity of a new chemical using a ToxCast data based model, its ToxCast bioactivity data are needed but not normally available. The capability of predicting ToxCast bioactivity data is necessary to fully utilize ToxCast data in the risk assessment of chemicals.

Objectives: We aimed to understand and elucidate the relationships between the chemicals and bioactivity data of the assays in ToxCast and to develop a network analysis based method for predicting ToxCast bioactivity data.

Methods: We conducted modularity analysis on a quantitative network constructed from ToxCast data to explore the relationships between the assays and chemicals. We further developed Nebula (neighbor-edges based and unbiased leverage algorithm) for predicting ToxCast bioactivity data.

Results: Modularity analysis on the network constructed from ToxCast data yielded seven modules. Assays and chemicals in the seven modules were distinct. Leave-one-out cross-validation yielded a Q(2) of 0.5416, indicating ToxCast bioactivity data can be predicted by Nebula. Prediction domain analysis showed some types of ToxCast assay data could be more reliably predicted by Nebula than others.

Conclusions: Network analysis is a promising approach to understand ToxCast data. Nebula is an effective algorithm for predicting ToxCast bioactivity data, helping fully utilize ToxCast data in the risk assessment of chemicals.