Using Machine Learning Methods and Structural Alerts for Prediction of Mitochondrial Toxicity

Mol Inform. 2020 May;39(5):e2000005. doi: 10.1002/minf.202000005. Epub 2020 Mar 23.


Over the last few years more and more organ and idiosyncratic toxicities were linked to mitochondrial toxicity. Despite well-established assays, such as the seahorse and Glucose/Galactose assay, an in silico approach to mitochondrial toxicity is still feasible, particularly when it comes to the assessment of large compound libraries. Therefore, in silico approaches could be very beneficial to indicate hazards early in the drug development pipeline. By combining multiple endpoints, we derived the largest so far published dataset on mitochondrial toxicity. A thorough data analysis shows that molecules causing mitochondrial toxicity can be distinguished by physicochemical properties. Finally, the combination of machine learning and structural alerts highlights the suitability for in silico risk assessment of mitochondrial toxicity.

Keywords: Structure-activity relationships; Toxicology; machine learning; mitochondrial toxicity; structural alerts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computer Simulation
  • Databases, Chemical
  • Drug Discovery / methods*
  • Drug-Related Side Effects and Adverse Reactions* / metabolism
  • Machine Learning*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Quantitative Structure-Activity Relationship