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A fundamental challenge in calcium imaging has been to infer the timing of action potentials from the measured noisy calcium fluorescence traces. We systematically evaluate a range of spike inference algorithms on a large benchmark dataset recorded f rom varying neural tissue (V1 and retina) using different calcium indicators (OGB-1 and GCamp6). We show that a new algorithm based on supervised learning in flexible probabilistic models outperforms all previously published techniques, setting a new standard for spike inference from calcium signals. Importantly, it performs better than other algorithms even on datasets not seen during training. Future data acquired in new experimental conditions can easily be used to further improve its spike prediction accuracy and generalization performance. Finally, we show that comparing algorithms on artificial data is not informative about performance on real population imaging data, suggesting that a benchmark dataset may greatly facilitate future algorithmic developments.
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