XML-CIMT: Explainable machine learning (XML) model for predicting chemical-induced mitochondrial toxicity

Keerthana Jaganathan, Mobeen Ur Rehman, Hilal Tayara*, Kil To Chong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
3 Downloads (Pure)


Organ toxicity caused by chemicals is a serious problem in the creation and usage of chemicals such as medications, insecticides, chemical products, and cosmetics. In recent decades, the initiation and development of chemical-induced organ damage have been related to mitochondrial dysfunction, among several adverse effects. Recently, many drugs, for example, troglitazone, have been removed from the marketplace because of significant mitochondrial toxicity. As a result, it is an urgent requirement to develop in silico models that can reliably anticipate chemical-induced mitochondrial toxicity. In this paper, we have proposed an explainable machine-learning model to classify mitochondrially toxic and non-toxic compounds. After several experiments, the Mordred feature descriptor was shortlisted to be used after feature selection. The selected features used with the CatBoost learning algorithm achieved a prediction accuracy of 85% in 10-fold cross-validation and 87.1% in independent testing. The proposed model has illustrated improved prediction accuracy when compared with the existing state-of-the-art method available in the literature. The proposed tree-based ensemble model, along with the global model explanation, will aid pharmaceutical chemists in better understanding the prediction of mitochondrial toxicity.
Original languageEnglish
Article number15655
Number of pages12
JournalInternational Journal of Molecular Sciences
Issue number24
Publication statusPublished - 9 Dec 2022
Externally publishedYes

Cite this