Morphology-based prediction of cancer cell migration using an artificial neural network and a random decision forest

Metastasis is the cause of death in most patients of breast cancer and other solid malignancies. Identification of cancer cells with highly migratory capability to metastasize relies on markers for epithelial-to-mesenchymal transition (EMT), a process increasing cell migration and metastasis. Marker-based approaches are limited by inconsistences among patients, types of cancer, and partial EMT states. Alternatively, we analyzed cancer cell migration behavior using computer vision. Using a microfluidic single-cell migration chip and high-content imaging, we extracted morphological features and recorded migratory direction and speed of breast cancer cells. By applying a Random Decision Forest (RDF) and an Artificial Neural Network (ANN), we achieved over 99% accuracy for cell movement direction prediction and 91% for speed prediction. Unprecedentedly, we identified highly motile cells and non-motile cells based on microscope images and a machine learning model, and pinpointed and validated morphological features determining cell migration, including not only known features related to cell polarization but also novel ones that can drive future mechanistic studies. Predicting cell movement by computer vision and machine learning establishes a ground-breaking approach to analyze cell migration and metastasis.