Improved automatic detection of herpesvirus secondary envelopment stages in electron microscopy by augmenting...

Detailed analysis of secondary envelopment of the herpesvirus human cytomegalovirus (HCMV) by transmission electron microscopy (TEM) is crucial for understanding the formation of infectious virions. Here, we present a convolutional neural network (CNN) that automatically recognises cytoplasmic capsids and distinguishes between three HCMV capsid envelopment stages in TEM images. 315 TEM images containing 2,610 expert-labelled capsids of the three classes were available for CNN training. To overcome the limitation of small training datasets and thus poor CNN performance, we used a deep learning method, the generative adversarial network (GAN), to automatically increase our labelled training dataset with 500 synthetic images and thus to 9,192 labelled capsids. The synthetic TEM images were added to the ground truth dataset to train the Faster R-CNN deep learning-based object detector. Training with 315 ground truth images yielded an average precision (AP) of 53.81% for detection, whereas the addition of 500 synthetic training images increased the AP to 76.48%. This shows that generation and additional use of synthetic labelled images for detector training is an inexpensive way to improve detector performance. This work combines the gold standard of secondary envelopment research with state-of-the-art deep learning technology to speed up automatic image analysis even when large labelled training datasets are not available.