Machine Learning Models to Predict Inhibition of the Bile Salt Export Pump

Cholestatic
liver injury is frequently associated with drug inhibition
of bile salt transporters, such as the bile salt export pump (BSEP).
Reliable in silico models to predict BSEP inhibition
directly from chemical structures would significantly reduce costs
during drug discovery and could help avoid injury to patients. We
report our development of classification and regression models for
BSEP inhibition with substantially improved performance over previously
published models. We assessed the performance effects of different
methods of chemical featurization, data set partitioning, and class
labeling and identified the methods producing models that generalized
best to novel chemical entities.