A self-supervised embedding of cell migration features for behavior discovery over cell populations

Recent studies point out that the dynamics and interaction of cell populations within their environment are related to several biological processes in immunology. Hence, single-cell analysis in immunology now relies on spatial omics. Moreover, recent literature suggests that immunology scenarios are hierarchically organized, including unknown cell behaviors appearing in different proportions across some observable control and therapy groups. These dynamic behaviors play a crucial role in identifying the causes of processes such as inflammation, aging, and fighting off pathogens or cancerous cells. In this work, we use a self-supervised learning approach to discover these behaviors associated with cell dynamics in an immunology scenario.

Specifically, we study the different responses of control group and therapy groups in a scenario involving inflammation due to infarct, with a focus on neutrophil migration within blood vessels. Starting from a set of hand-crafted spatio-temporal features, we use a recurrent neural network to generate embeddings that properly describe the dynamics of the migration processes. The network is trained using a novel multi-task contrastive loss that, on the one hand, models the hierarchical structure of our scenario (groups-behaviors-samples) and, on the other, ensures temporal consistency within the embedding, enforcing that subsequent temporal samples obtained from a given cell stay close in the latent space.

Our experimental results demonstrate that the resulting embeddings improve the separability of cell behaviors and log-likelihood of the therapies, when compared to the hand-crafted feature extraction and recent methods from the state of the art, even with dimensionality reduction (16 vs. 21 hand-crafted features).

Our approach enables single-cell analyses at a population level, being able to automatically discover shared behaviors among different groups. This, in turn, enables the prediction of the therapy effectiveness based on their proportions within a study group.