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pmid:35595235
Transcriptome-wide prediction of prostate cancer gene expression from histopathology images using co-expression-based convolutional neural networks.
Philippe Weitz · Yinxi Wang · Kimmo Kartasalo · Lars Egevad · Johan Lindberg · Henrik Grönberg · Martin Eklund · Mattias Rantalainen
Bioinformatics (Oxford, England) · 2022 doi:10.1093/bioinformatics/btac343
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Complete file
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Changes in gene expression occurring in tumours cause morphological changes in tissue, which can be observed on the microscopic level. The relationship between morphological patterns and some of the molecular phenotypes can be exploited to predict molecular phenotypes from routine haematoxylin and eosin-stained whole slide images (WSIs) using convolutional neural networks (CNNs). In this study, we propose a new, computationally efficient approach to model relationships between morphology and gene expression.\nRESULTS: We conducted the first transcriptome-wide analysis in prostate cancer, using CNNs to predict bulk RNA-sequencing estimates from WSIs for 370 patients from the TCGA PRAD study. Out of 15 586 protein coding transcripts, 6618 had predicted expression significantly associated with RNA-seq estimates (FDR-adjusted P-value <1×10-4) in a cross-validation and 5419 (81.9%) of these associations were subsequently validated in a held-out test set. We furthermore predicted the prognostic cell-cycle progression score directly from WSIs. These findings suggest that contemporary computer vision models offer an inexpensive and scalable solution for prediction of gene expression phenotypes directly from WSIs, providing opportunity for cost-effective large-scale research studies and molecular diagnostics.\nAVAILABILITY AND IMPLEMENTATION: A self-contained example is available from http://github.com/phiwei/prostate_coexpression. Model predictions and metrics are available from doi.org/10.5281/zenodo.4739097.\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "claims": [{"id": "claim-method", "statement": "Spearman rank correlations between the slide-level predictions and the RNA-seq expression level values were used as the primary performance metric.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35595235", "locator": "sections[6] \"2.4 Model optimization and performance evaluation\" paragraph 5", "quote": "Spearman rank correlations between the slide-level predictions and the RNA-seq expression level values were used as the primary performance metric."}], "state": "complete"}, {"id": "claim-data-access", "statement": "WSIs, RNA-seq and clinical data for the TCGA PRAD cohort are publicly available from the GDC data portal (https://portal.gdc.cancer.gov/). 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