Predicting tumour mutational burden from histopathological images using multiscale deep learning

Tumour mutational burden (TMB) is an important biomarker for predicting the response to immunotherapy in patients with cancer. Gold-standard measurement of TMB is performed using whole exome sequencing (WES), which is not available at most hospitals because of its high cost, operational complexity and long turnover times. We have developed a machine learning algorithm, Image2TMB, which can predict TMB from readily available lung adenocarcinoma histopathological images. Image2TMB integrates the predictions of three deep learning models that operate at different resolution scales (x5, x10 and x20 magnification) to determine if the TMB of a cancer is high or low. On a held-out set of patients, Image2TMB achieves an area under the precision recall curve of 0.92, an average precision of 0.89, and has the predictive power of a targeted sequencing panel of similar to 100 genes. This study demonstrates that it is possible to infer genomic features from histopathology images, and potentially opens avenues for exploring genotype-phenotype relationships.