Pixel precise unsupervised detection of viral particle proliferation in cellular imaging data

Cellular and molecular imaging techniques and models have been developed to characterize single stages of viral proliferation after focal infection of cells in vitro. The fast and automatic classification of cell imaging data may prove helpful prior to any further comparison of representative experimental data to mathematical models of viral propagation in host cells. Here, we use computer generated images drawn from a reproduction of an imaging model from a previously published study of experimentally obtained cell imaging data representing progressive viral particle proliferation in host cell monolayers. Inspired by experimental time-based imaging data, here in this study viral particle increase in time is simulated by a one-by-one increase, across images, in black or gray single pixels representing dead or partially infected cells, and hypothetical remission by a one-by-one increase in white pixels coding for living cells in the original image model. The image simulations are submitted to unsupervised learning by a Self-Organizing Map (SOM) and the Quantization Error in the SOM output (SOM-QE) is used for automatic classification of the image simulations as a function of the represented extent of viral particle proliferation or cell recovery. Unsupervised classification by SOM-QE of 160 model images, each with more than three million pixels, is shown to provide a statistically reliable, pixel precise, and fast classification model that outperforms human computer-assisted image classification by RGB image mean computation. The automatic classification procedure proposed here provides a powerful approach to understand finely tuned mechanisms in the infection and proliferation of virus in cell lines in vitro or other cells.