Spatial-context-aware RNA-sequence prediction from head and neck cancer histopathology images.

Abstract

Molecular profiling of the tumor in addition to the histological tumor analysis can provide robust information for targeted cancer therapies. Often such data are not available for analysis due to processing delays, cost or inaccessibility. In this paper, we proposed a deep learning-based method to predict RNA-sequence expression (RNA-seq) from Hematoxylin and Eosin whole-slide images (H&E WSI) in head and neck cancer patients. Conventional methods utilize a patch-by-patch prediction and aggregation strategy to predict RNA-seq at a whole-slide level. However, these methods lose spatial-contextual relationships between patches that comprise morphology interactions crucial for predicting RNA-seq. We proposed a novel framework that employs a neural image compressor to preserve the spatial relationships between patches and generate a compressed representation of the whole-slide image, and a customized deep-learning regressor to predict RNA-seq from the compressed representation by learning both global and local features. We tested our proposed method on publicly available TCGA-HNSC dataset comprising 43 test patients for 10 oncogenes. Our experiments showed that the proposed method achieves a 4.12% higher mean correlation and predicts 6 out of 10 genes with better correlation than a state-of-the-art baseline method. Furthermore, we provided interpretability using pathway analysis of the best-predicted genes, and activation maps to highlight the regions in an H&E image that are the most salient of the RNA-seq prediction.Clinical relevance-The proposed method has the potential to discover genetic biomarkers directly from the histopathology images which could be used to pre-screen the patients before actual genetic testing thereby saving cost and time.