Weakly-supervised tumor purity prediction from frozen H&E stained slides

BACKGROUND: Estimating tumor purity is especially important in the age of precision medicine. Purity estimates have been shown to be critical for correction of tumor sequencing results, and higher purity samples allow for more accurate interpretations from next-generation sequencing results. Molecular-based purity estimates using computational approaches require sequencing of tumors, which is both time-consuming and expensive. METHODS: Here we propose an approach, weakly-supervised purity (wsPurity), which can accurately quantify tumor purity within a digitally captured hematoxylin and eosin (H&E) stained histological slide, using several types of cancer from The Cancer Genome Atlas (TCGA) as a proof-of-concept. FINDINGS: Our model predicts cancer type with high accuracy on unseen cancer slides from TCGA and shows promising generalizability to unseen data from an external cohort (F1-score of 0.83 for prostate adenocarcinoma). In addition we compare performance of our model on tumor purity prediction with a comparable fully-supervised approach on our TCGA held-out cohort and show our model has improved performance, as well as generalizability to unseen frozen slides (0.1543 MAE on an independent test cohort). In addition to tumor purity prediction, our approach identified high resolution tumor regions within a slide, and can also be used to stratify tumors into high and low tumor purity, using different cancer-dependent thresholds. INTERPRETATION: Overall, we demonstrate our deep learning model's different capabilities to analyze tumor H&E sections. We show our model is generalizable to unseen H&E stained slides from data from TCGA as well as data processed at Weill Cornell Medicine. FUNDING: Starr Cancer Consortium Grant (SCC I15-0027) to Iman Hajirasouliha.