Analysis of chemical and biological features yields mechanistic insights into drug side effects.

Side effects (SEs) are the unintended consequence of therapeutic treatments, but they can also be seen as valuable readouts of drug effects, resulting from the perturbation of biological systems by chemical compounds. Unfortunately, biology and chemistry are often considered separately, leading to incomplete models unable to provide a unified view of SEs. Here, we investigate the molecular bases of over 1,600 SEs by navigating both chemical and biological spaces. We identified characteristic molecular traits for 1,162 SEs, 38% of which can be explained using solely biological arguments, and only 6% are exclusively associated with the chemistry of the compounds, implying that the drug action is somewhat unspecific. Overall, we provide mechanistic insights for most SEs and emphasize the need to blend biology and chemistry to surpass intricate phenomena not captured in the molecular biology view.