Abstract
Molecular alterations in malignant tumors can cause phenotypic changes in tumor cells and their microenvironment. Routine histopathology tissue slides – which are ubiquitously available for patients with solid tumors – can reflect such morphological changes. Here, we show that deep learning can consistently infer a wide range of genetic mutations, molecular tumor subtypes, gene expression signatures and standard pathology biomarkers directly from routine histology images of cancer. We developed, systematically optimized, validated and publicly released a one-stop-shop workflow and applied it to routine tissue slides of more than 5000 patients across a broad spectrum of common solid tumors including lung, colorectal, breast and gastric cancer. Our findings show that a single deep learning algorithm can be trained to predict a wide range of molecular alterations from routine, paraffin-embedded histology slides stained with hematoxylin and eosin. These predictions generalize to other populations and yield spatially resolved predictions. Our method can be implemented on mobile hardware, potentially enabling point-of-care diagnostics for personalized cancer treatment. More generally, this approach can be used to elucidate and quantify genotype-phenotype links in cancer.
Original language | English |
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Pages (from-to) | 789-799 |
Number of pages | 11 |
Journal | Nature Cancer |
Volume | 1 |
Issue number | 8 |
Early online date | 27 Jul 2020 |
DOIs | |
Publication status | Published - Aug 2020 |
Bibliographical note
FundingThe results are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. Our funding sources are as follows. J.N.K.: RWTH University Aachen (START 2018-691906). V.S.: Breast Cancer Now, P.Bo: DFG: (SFB/TRR57, SFB/TRR219, BO3755/3-1, and BO3755/6-1), the German Ministry of Education and Research (BMBF: STOP-FSGS-01GM1901A) and the German Ministry of Economic Affairs and Energy (BMWi: EMPAIA project). A.T.P.: NIH/NIDCR (#K08-DE026500), Institutional Research Grant (#IRG-16-222-56) from the American Cancer Society, Cancer Research Foundation Research Grant, and the University of Chicago Med470 icine Comprehensive Cancer Center Support Grant (#P30-CA14599). T.L.: Horizon 2020 through the European Research Council (ERC) Consolidator Grant PhaseControl (771083), a Mildred Scheel-Endowed Professorship from the German Cancer Aid (Deutsche Krebshilfe), the German Research Foundation (DFG) (SFB CRC1382/P01, SFB-TRR57/P06, LU 1360/3-1), the Ernst-Jung Foundation Hamburg and the IZKF (interdisciplinary center of clinical research) at RWTH Aachen.
Correction to: Nature Cancer https://doi.org/10.1038/s43018-020-0087-6, published online 27 July 2020. https://doi.org/10.1038/s43018-020-00149-6
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Valerie Speirs
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Chair in Molecular Oncology
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cancer Centre
Person: Academic