Faculty, Staff and Student Publications

Publication Date

9-19-2023

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2023.101173

PMID

37582371

PMCID

PMC10518635

PubMedCentral® Posted Date

9-19-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Proteogenomics, Deep Learning, Neoplasms, Proteomics, Machine Learning, computational pathology, cancer proteogenomics, cancer imaging, CPTAC, molecular diagnostics

Published Open-Access

yes

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