Obtaining Spatially Resolved Tumor Purity Maps Using Deep Multiple Instance Learning In A Pan-cancer Study

Abstract

Tumor purity is the proportion of cancer cells in the tumor tissue. An accurate tumor purity estimation is crucial for accurate pathologic evaluation and for sample selection to minimize normal cell contamination in high throughput genomic analysis. We developed a novel deep multiple instance learning model predicting tumor purity from H&E stained digital histopathology slides. Our model successfully predicted tumor purity from slides of fresh-frozen sections in eight different TCGA cohorts and formalin-fixed paraffin-embedded sections in a local Singapore cohort. The predictions were highly consistent with genomic tumor purity values, which were inferred from genomic data and accepted as the golden standard. Besides, we obtained spatially resolved tumor purity maps and showed that tumor purity varies spatially within a sample. Our analyses on tumor purity maps also suggested that pathologists might have chosen high tumor content regions inside the slides during tumor purity estimation in the TCGA cohorts, which resulted in higher values than genomic tumor purity values. In short, our model can be utilized for high throughput sample selection for genomic analysis, which will help reduce pathologists workload and decrease inter-observer variability. Moreover, spatial tumor purity maps can help better understand the tumor microenvironment as a key determinant in tumor formation and therapeutic response.