A pre-trained fully convolutional VGG-16, FCN-8 network was trained to segment histology images into five classes: tumor, stroma, inflammatory infiltrates, necrosis and other classes (Long et al., 2015 ). Shift and crop data augmentation was used to improve model robustness—see Supplementary Methods for details. Focusing on the 125 ROIs from infiltrating ductal carcinomas [the majority of TNBCs (Plasilova et al., 2016 (link))], we first applied color normalization to the RGB images of the ROIs (Reinhard et al., 2001 ). Several different types of models were trained to evaluate different aspects of crowdsourcing:
Firstly, to investigate the effects of using crowdsourced versus single-expert annotations for training, we trained ‘comparison’ models for semantic segmentation. These models used annotations from evaluation set ROIs for training, and were evaluated on the post-correction core-set annotations (see Supplementary Fig. S2C).
Second, to evaluate peak accuracy, we trained ‘full’ models for semantic segmentation using the largest amounts of crowdsourced annotations possible. The full models were trained using annotations from core-set ROIs, assigning the ROIs from 82 slides (from 11 institutes) to the training set, and the ROIs from 43 slides (from seven institutes) to the testing set. Strict separation of ROIs by institute into either training or testing provides a better measure of how models developed with our data will generalize to slides from new institutions and multi-institute studies.
Finally, to evaluate the effect of training set size on the accuracy of predictive models, we developed ‘scale-dependent’ image classification models using varying amounts of our crowdsourced annotation data (Supplementary Fig S5). Since training hundreds of semantic segmentation models is time prohibitive, we instead trained classification models based on the pre-trained VGG-16 network to classify 224×224 pixel patches from the three predominant classes: tumor, stroma and inflammatory infiltration, using the same train/test assignment used in the semantic segmentation model (see details in Supplementary Methods).
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