Self-supervised machine learning for live cell imagery segmentation

Segmenting single cells is a necessary process for extracting quantitative data from biological microscopy imagery. The past decade has seen the advent of machine learning (ML) methods to aid in this process, the overwhelming majority of which fall under supervised learning (SL) which requires vast libraries of pre-processed, human-annotated labels to train the ML algorithms. Such SL pre-processing is labor intensive, can introduce bias, varies between end-users, and has yet to be shown capable of robust models to be effectively utilized throughout the greater cell biology community. Here, to address this pre-processing problem, we offer a self-supervised learning (SSL) approach that utilizes cellular motion between consecutive images to self-train a ML classifier, enabling cell and background segmentation without the need for adjustable parameters or curated imagery. By leveraging motion, we achieve accurate segmentation that trains itself directly on end-user data, is independent of optical modality, outperforms contemporary SL methods, and does so in a completely automated fashion—thus eliminating end-user variability and bias. To the best of our knowledge, this SSL algorithm represents a first of its kind effort and has appealing features that make it an ideal segmentation tool candidate for the broader cell biology research community.