Oxidopamine-Induced Nuclear Alterations Quantified Using Advanced Fractal Analysis: Random Forest Machine Learning Approach

Igor Pantic, Nikola Topalovic, Peter R. Corridon, Jovana Paunovic

Fractal analysis (FA) is a contemporary computational technique that can assist in identifying and assessing nuanced structural alterations in cells and tissues after exposure to certain toxic chemical agents. Its application in toxicology may be particularly valuable for quantifying structural changes in cell nuclei during conventional microscopy assessments. In recent years, the fractal dimension and lacunarity of cell nuclei, considered among the most significant FA features, have been suggested as potentially important indicators of cell damage and death. In this study, we demonstrate the feasibility of developing a random forest machine learning model that employs fractal indicators as input data to identify yeast cells treated with oxidopamine (6-hydroxydopamine, 6-OHDA), a powerful toxin commonly applied in neuroscience research. The model achieves notable classification accuracy and discriminatory power, with an area under the receiver operating characteristics curve of more than 0.8. Moreover, it surpasses alternative decision tree models, such as the gradient-boosting classifier, in differentiating treated cells from their intact counterparts. Despite the methodological challenges associated with fractal analysis and random forest training, this approach offers a promising avenue for the continued exploration of machine learning applications in cellular physiology, pathology, and toxicology.