CellDeathPred: a deep learning framework for ferroptosis and apoptosis prediction based on cell painting

Cell death, such as apoptosis and ferroptosis, play essential roles in the process of development, homeostasis, and pathogenesis of acute and chronic diseases. The increasing number of studies investigating cell death types in various diseases, particularly cancer and degenerative diseases, has raised hopes for their modulation in disease therapies. However, identifying the presence of a particular cell death type is not an obvious task, as it requires computationally intensive work and costly experimental assays. To address this challenge, we present CellDeathPred, a novel deep-learning framework that uses high-content imaging based on cell painting to distinguish cells undergoing ferroptosis or apoptosis from healthy cells. In particular, we incorporate a deep neural network that effectively embeds microscopic images into a representative and discriminative latent space, classifies the learned embedding into cell death modalities, and optimizes the whole learning using the supervised contrastive loss function. We assessed the efficacy of the proposed framework using cell painting microscopy data sets from human HT-1080 cells, where multiple inducers of ferroptosis and apoptosis were used to trigger cell death. Our model confidently separates ferroptotic and apoptotic cells from healthy controls, with an average accuracy of 95% on non-confocal data sets, supporting the capacity of the CellDeathPred framework for cell death discovery.

Automated summary

Cell death, including apoptosis and ferroptosis, plays a crucial role in development, homeostasis, and the pathogenesis of diseases. The ability to modulate different cell death types offers promising therapeutic opportunities. However, identifying specific cell death types is a challenging task that requires computational analysis and costly experimental assays. In this study, we introduce CellDeathPred, a deep-learning framework that uses high-content imaging to distinguish between ferroptotic or apoptotic cells and healthy cells. Our framework effectively embeds microscopic images and classifies them into different cell death modalities, providing a new tool for cell death discovery and research.