A transformer-based weakly supervised computational pathology method for clinical-grade diagnosis and molecular marker discovery of gliomas

The complex diagnostic criteria for gliomas pose great challenges for making accurate diagnoses with computational pathology methods. There are no in-depth analyses of the accuracy, reliability and auxiliary capability of present approaches from a clinical perspective. Previous studies have overlooked the exploration of molecular and morphological correlations. To overcome these limitations, we propose ROAM, a multiple-instance learning model based on large regions of interest and a pyramid transformer. ROAM enlarges regions of interest to facilitate the consideration of tissue contexts. It utilizes the pyramid transformer to model both intrascale and interscale correlations of morphological features and leverages class-specific multiple-instance learning based on attention to extract slide-level visual representations that can be used to diagnose gliomas. Through comprehensive experiments on both in-house and external glioma datasets, we demonstrate that ROAM can automatically capture key morphological features consistent with the experience of pathologists and thus provide accurate, reliable and adaptable clinical-grade diagnoses of gliomas. Moreover, ROAM has clinical value for auxiliary diagnoses and could pave the way for the study of molecular and morphological correlations. ROAM, based on large regions of interest and a pyramid transformer, can automatically capture key morphological features consistent with the experience of pathologists to provide accurate, reliable and adaptable clinical-grade diagnoses of gliomas while advancing the discovery of molecular and morphological markers related to glioma diagnosis.