Direct Gene Expression Profile Prediction for Uveal Melanoma from Digital Cytopathology Images via Deep Learning and Salient Image Region Identification

To demonstrate that deep learning (DL) methods can produce robust prediction of gene expression profile (GEP) in uveal melanoma (UM) based on digital cytopathology images. Evaluation of a diagnostic test or technology. Deidentified smeared cytology slides stained with hematoxylin and eosin obtained from a fine needle aspirated from UM. Digital whole-slide images were generated by fine-needle aspiration biopsies of UM tumors that underwent GEP testing. A multistage DL system was developed with automatic region-of-interest (ROI) extraction from digital cytopathology images, an attention-based neural network, ROI feature aggregation, and slide-level data augmentation. The ability of our DL system in predicting GEP on a slide (patient) level. Data were partitioned at the patient level (73% training; 27% testing). In total, our study included 89 whole-slide images from 82 patients and 121 388 unique ROIs. The testing set included 24 slides from 24 patients (12 class 1 tumors; 12 class 2 tumors; 1 slide per patient). Our DL system for GEP prediction achieved an area under the receiver operating characteristic curve of 0.944, an accuracy of 91.7%, a sensitivity of 91.7%, and a specificity of 91.7% on a slide-level analysis. The incorporation of slide-level feature aggregation and data augmentation produced a more predictive DL model (P = 0.0031). Our current work established a complete pipeline for GEP prediction in UM tumors: from automatic ROI extraction from digital cytopathology whole-slide images to slide-level predictions. Our DL system demonstrated robust performance and, if validated prospectively, could serve as an image-based alternative to GEP testing.