1. Deep learning integrates histopathology and proteogenomics at a pan-cancer level.
- Author
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Wang JM, Hong R, Demicco EG, Tan J, Lazcano R, Moreira AL, Li Y, Calinawan A, Razavian N, Schraink T, Gillette MA, Omenn GS, An E, Rodriguez H, Tsirigos A, Ruggles KV, Ding L, Robles AI, Mani DR, Rodland KD, Lazar AJ, Liu W, and Fenyö D
- Subjects
- Humans, Proteomics, Machine Learning, Proteogenomics, Deep Learning, Neoplasms genetics
- Abstract
We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) and tissue-of-origin (AUROC = 0.979). We further investigate predictive power on tasks not normally performed from H&E alone, including TP53 prediction and pathologic stage. Importantly, we describe predictive morphologies not previously utilized in a clinical setting. The incorporation of transcriptomics and proteomics identifies pathway-level signatures and cellular processes driving predictive histology features. Model generalizability and interpretability is confirmed using TCGA. We propose a classification system for these tasks, and suggest potential clinical applications for this integrated human and machine learning approach. A publicly available web-based platform implements these models., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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