Deep learning identifies heterogeneous subpopulations in breast cancer cell lines

Cells exhibit a wide array of morphological features, enabling computer vision methods to identify and track relevant parameters. Morphological analysis has long been implemented to identify specific cell types and cell responses. Here, we asked whether morphological features might also be used to classify transcriptomic subpopulations within in vitro cancer cell lines. Identifying cell subpopulations furthers our understanding of morphology as a reflection of underlying cell phenotype and could enable a better understanding of how subsets of cells compete and cooperate in disease progression and treatment. We demonstrate that cell morphology can reflect underlying transcriptomic differences in vitro using convolutional neural networks. First, we find that changes induced by chemotherapy treatment are highly identifiable in a breast cancer cell line. We then show that the intra cell line subpopulations that comprise breast cancer cell lines under standard growth conditions are also identifiable using cell morphology. We find that cell morphology is influenced by neighborhood effects beyond the cell boundary, and that including image information surrounding the cell can improve model discrimination ability.