Calcium Spark Detection and Event-Based Classification of Single Cardiomyocyte Using Deep Learning.

Abstract

Ca2+ sparks are the elementary Ca2+ release events in cardiomyocytes, altered properties of which lead to impaired Ca2+ handling and finally contribute to cardiac pathology under various diseases. Despite increasing use of machine-learning algorithms in deciphering the content of biological and medical data, Ca2+ spark images and data are yet to be deeply learnt and analyzed. In the present study, we developed a deep residual convolutional neural network method to detect Ca2+ sparks. Compared to traditional detection methods with arbitrarily defined thresholds to distinguish signals from noises, our new method detected more Ca2+ sparks with lower amplitudes but similar spatiotemporal distributions, thereby indicating that our new algorithm detected many very weak events that are usually omitted when using traditional detection methods. Furthermore, we proposed an event-based logistic regression and binary classification model to classify single cardiomyocytes using Ca2+ spark characteristics, which to date have generally been used only for simple statistical analyses and comparison between normal and diseased groups. Using this new detection algorithm and classification model, we succeeded in distinguishing wild type (WT) vs RyR2-R2474S± cardiomyocytes with 100% accuracy, and vehicle vs isoprenaline-insulted WT cardiomyocytes with 95.6% accuracy. The model can be extended to judge whether a small number of cardiomyocytes (and so the whole heart) are under a specific cardiac disease. Thus, this study provides a novel and powerful approach for the research and application of calcium signaling in cardiac diseases.