Automated quantification of morphodynamics for high-throughput live cell time-lapse datasets

We present a fully automatic method to track and quantify the morphodynamics of differentiating neurons in fluorescence time-lapse datasets. Previous high-throughput studies have been limited to static analysis or simple behavior. Our approach opens the door to rich dynamic analysis of complex cellular behavior in high-throughput time-lapse data. It is capable of robustly detecting, tracking, and segmenting all the components of the neuron including the nucleus, soma, neurites, and filopodia. It was designed to be efficient enough to handle the massive amount of data from a high-throughput screen. Each image is processed in approximately two seconds on a notebook computer. To validate the approach, we applied our method to over 500 neuronal differentiation videos from a small-scale RNAi screen. Our fully automated analysis of over 7,000 neurons quantifies and confirms with strong statistical significance static and dynamic behaviors that had been previously observed by biologists, but never measured.