The challenges of generalizability in artificial intelligence for ADME/Tox endpoint and activity prediction

Artificial intelligence (AI) has seen a massive resurgence in recent years with wide successes in computer vision, natural language processing, and games. The similar creation of robust and accurate AI models for ADME/Tox endpoint and activity prediction would be revolutionary to drug discovery pipelines. There have been numerous demonstrations of successful applications, but a key challenge remains: how generalizable are these predictive models?

The authors present a summary of current promising components of AI models in the context of early drug discovery where ADME/Tox endpoint and activity prediction is the main driver of the iterative drug design process. Following that is a review of applicability domains and dataset construction considerations which determine generalizability bottlenecks for AI deployment. Further reviewed is the role of promising learning frameworks - multitask, transfer, and meta learning - which leverage auxiliary data to overcome issues of generalizability.

The authors conclude that the most promising direction toward integrating reliable and informative AI models into the drug discovery pipeline is a conjunction of learned feature representations, deep learning, and novel learning frameworks. Such a solution would address the sparse and incomplete datasets that are available for key endpoints related to drug discovery.