Proteomics data encode molecular features of diagnostic value and accurately reflect key underlying biological mechanisms in cancers. Histopathology imaging is a well-established clinical approach to cancer diagnosis. The predictive relationship between large-scale proteomics and H&E-stained histopathology images remains largely uncharacterized. Here we investigate such associations through the application of machine learning, including deep neural networks, to proteomics and histology imaging datasets generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) from clear cell renal cell carcinoma patients. We report robust correlations between a set of diagnostic proteins and predictions generated by an imaging-based classification model. Proteins significantly correlated with the histology-based predictions are significantly implicated in immune responses, extracellular matrix reorganization, and metabolism. Moreover, we showed that the genes encoding these proteins also reliably recapitulate the biological associations with imaging-derived predictions based on strong gene–protein expression correlations. Our findings offer novel insights into the integrative modeling of histology and omics data through machine learning, as well as the methodological basis for new research opportunities in this and other cancer types.
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