The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Pan-cancer image-based detection of clinically actionable genetic alterations
Open accessPublished version of a preprint
Abstract
Molecular alterations in cancer can cause phenotypic changes in tumor cells and their micro-environment. Routine histopathology tissue slides - which are ubiquitously available - 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. We developed, optimized, validated and publicly released a one-stop-shop workflow and applied it to tissue slides of more than 5000 patients across multiple solid tumors. 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 are spatially resolved. Our method can be implemented on mobile hardware, potentially enabling point-of-care diagnostics for personalized cancer treatment. More generally, this approach could elucidate and quantify genotype-phenotype links in cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Deep Residual Learning for Image Recognition
He, K., Zhang, X., Ren, S., & Sun, J. (2016) · 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) · doi:10.1109/cvpr.2016.90 · Cited by 235,474
Densely Connected Convolutional Networks
Huang, G., Liu, Z., Van Der Maaten, L., & Weinberger, K. Q. (2017) · 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) · doi:10.1109/cvpr.2017.243 · Cited by 48,566
Rethinking the Inception Architecture for Computer Vision
Szegedy, C., Vanhoucke, V., Ioffe, S., Shlens, J., & Wojna, Z. (2016) · 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) · doi:10.1109/cvpr.2016.308 · Cited by 32,138
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
QuPath: Open source software for digital pathology image analysis
Bankhead, P., Loughrey, M. B., Fernández, J. A., Dombrowski, Y., McArt, D. G., Dunne, P. D., McQuaid, S., Gray, R. T., Murray, L. J., Coleman, H. G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17204-5 · Cited by 8,908
Self-citationComprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Research works printed but not linked: 27
- Cheng, M. L., Berger, M. F., Hyman, D. M. & Solit, D. B. Clinical tumour sequencing for precision oncology: time for a universal strategy. Nat. Rev. Cancer 18, 527–528 (2018). · DOI
- Rusch, M. et al. Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome. Nat. Commun. 9, 3962 (2018). · DOI
- Kather, J. N., Halama, N. & Jaeger, D. Genomics and emerging biomarkers for immunotherapy of colorectal cancer. Semin. Cancer Biol. 52, 189–197 (2018). · DOI
- Guinney, J. et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 21, 1350–1356 (2015). · DOI · Paper page
- Fontana, E., Eason, K., Cervantes, A., Salazar, R. & Sadanandam, A. Context matters—consensus molecular subtypes of colorectal cancer as biomarkers for clinical trials. Ann. Oncol. 30, 520–527 (2019). · DOI
- Shia, J. et al. Morphological characterization of colorectal cancers in The Cancer Genome Atlas reveals distinct morphology–molecular associations: clinical and biological implications. Modern Pathol. 30, 599–609 (2017). · DOI · Paper page
- Schaumberg, A. J., Rubin, M. A. & Fuchs, T. J. H&E-stained whole slide image deep learning predicts SPOP mutation state in prostate cancer. Preprint at bioRxiv https://doi.org/10.1101/064279 (2018). · DOI
- Kather, J. N. et al. Deep learning detects virus presence in cancer histology. Preprint at bioRxiv https://doi.org/10.1101/690206 (2019). · DOI
- Zhang, H. et al. Predicting tumor mutational burden from liver cancer pathological images using convolutional neural network. In 2019 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 920–925 (Institute of Electrical and Electronics Engineers, 2019); https://doi.org/10.1109/BIBM47256.2019.8983139 · DOI
- Campanella, G. et al. Clinical-grade computational pathology using weakly supervised deep learning on whole slide images. Nat. Med. 25, 1301–1309 (2019). · DOI · Paper page
- Zhang, X., Zhou, X., Lin, M. & Sun, J. ShuffleNet: an extremely efficient convolutional neural network for mobile devices. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition 6848–6856 (Institute of Electrical and Electronics Engineers, 2018); https://doi.org/10.1109/CVPR.2018.00716 · DOI · Paper page
- Chen, P. C. et al. An augmented reality microscope with real-time artificial intelligence integration for cancer diagnosis. Nat. Med. 25, 1453–1457 (2019). · DOI · Paper page
- Fukamachi, H. et al. A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors. J. Exp. Clin. Cancer Res. 38, 127 (2019). · DOI
- Xue, Z. et al. MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models. Cell Res. 28, 719–729 (2018). · DOI
- Khalaf, A. M. et al. Role of Wnt/β-catenin signaling in hepatocellular carcinoma, pathogenesis, and clinical significance. J. Hepatocell. Carcinoma 5, 61–73 (2018). · DOI
- Davis, C. F. et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell 26, 319–330 (2014). · DOI · Paper page
- The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576–582 (2015). · DOI · Paper page
- Li, C., Egloff, A. M., Sen, M., Grandis, J. R. & Johnson, D. E. Caspase-8 mutations in head and neck cancer confer resistance to death receptor-mediated apoptosis and enhance migration, invasion, and tumor growth. Mol. Oncol. 8, 1220–1230 (2014). · DOI
- Burk, R. D. et al. Integrated genomic and molecular characterization of cervical cancer. Nature 543, 378–384 (2017). · DOI · Paper page
- Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812–830.e14 (2018). · DOI · Paper page
- Liu, Y. et al. Comparative molecular analysis of gastrointestinal adenocarcinomas. Cancer Cell 33, 721–735.e8 (2018). · DOI · Paper page
- Barresi, V., Bonetti, L. R. & Bettelli, S. KRAS, NRAS, BRAF mutations and high counts of poorly differentiated clusters of neoplastic cells in colorectal cancer: observational analysis of 175 cases. Pathology 47, 551–556 (2015). · DOI
- Hoffmeister, M. et al. Statin use and survival after colorectal cancer: the importance of comprehensive confounder adjustment. J. Natl Cancer Inst. 107, djv045 (2015). · DOI
- Brenner, H., Chang-Claude, J., Seiler, C. M. & Hoffmeister, M. Long-term risk of colorectal cancer after negative colonoscopy. J. Clin. Oncol. 29, 3761–3767 (2011). · DOI
- Gao, J. et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal 6, pl1 (2013). · DOI · Paper page
- Berger, A. C. et al. A comprehensive pan-cancer molecular study of gynecologic and breast cancers. Cancer Cell 33, 690–705.e9 (2018). · DOI · Paper page
- Bianconi, F., Kather, J. N. & Reyes-Aldasoro, C. C. Evaluation of colour pre-processing on patch-based classification of H&E-stained images. In European Congress on Digital Pathology (eds. Reyes-Aldasoro, C. et al.) 56–64 (Lecture Notes in Computer Science Volume 11435, Springer, 2019). · DOI
Cited by
Data-efficient and weakly supervised computational pathology on whole-slide images
Lu, M. Y., Williamson, D. F. K., Chen, T. Y., Chen, R. J., Barbieri, M., & Mahmood, F. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00682-w · Cited by 2,282
Towards a general-purpose foundation model for computational pathology
Chen, R. J., Ding, T., Lu, M. Y., Williamson, D. F. K., Jaume, G., Song, A. H., Chen, B., Zhang, A., Shao, D., Shaban, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02857-3 · Cited by 1,560
A visual-language foundation model for computational pathology
Lu, M. Y., Chen, B., Williamson, D. F. K., Chen, R. J., Liang, I., Ding, T., Jaume, G., Odintsov, I., Le, L. P., Gerber, G., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02856-4 · Cited by 966
Deep learning in cancer diagnosis, prognosis and treatment selection
Tran, K. A., Kondrashova, O., Bradley, A., Williams, E. D., Pearson, J. V., & Waddell, N. (2021) · Genome Medicine · doi:10.1186/s13073-021-00968-x · Cited by 932
Deep learning in histopathology: the path to the clinic
van der Laak, J., Litjens, G., & Ciompi, F. (2021) · Nature Medicine · doi:10.1038/s41591-021-01343-4 · Cited by 902
Metadata
- Authors
- Kather, J. N., Heij, L. R., Grabsch, H. I., Loeffler, C., Echle, A., Muti, H. S., Krause, J., Niehues, J. M., Sommer, K. A. J., Bankhead, P., Kooreman, L. F. S., Schulte, J. J., Cipriani, N. A., Buelow, R. D., Boor, P., Ortiz-Brüchle, N., Hanby, A. M., Speirs, V., Kochanny, S., Patnaik, A., Srisuwananukorn, A., Brenner, H., Hoffmeister, M., van den Brandt, P. A., Jäger, D., Trautwein, C., Pearson, A. T., & Luedde, T.
- Venue
- Nature Cancer
- Published
- 2020-07-27
- Volume
- 1
- Issue
- 8
- Pages
- 789-799
- ISSN
- 2662-1347 (ISSN-L)
- OpenAlex
- W3044996171
- Cited by
- 662
- References
- 24
- FWCI
- 32.30
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-11-03)
- Open access
- hybrid
- Licence
- www.springernature.com/gp/researchers/text-and-data-mining (tdm)
- www.springernature.com/gp/researchers/text-and-data-mining (vor)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Pan-cancer image-based detection of clinically actionable genetic alterations. https://app.cochat.ai/papers/10.1038/s43018-020-0087-6
- The paper
- Kather, J. N., Heij, L. R., Grabsch, H. I., Loeffler, C., Echle, A., Muti, H. S., Krause, J., Niehues, J. M., Sommer, K. A. J., Bankhead, P., Kooreman, L. F. S., Schulte, J. J., Cipriani, N. A., Buelow, R. D., Boor, P., Ortiz-Brüchle, N., Hanby, A. M., Speirs, V., Kochanny, S., . . . Luedde, T. (2020). Pan-cancer image-based detection of clinically actionable genetic alterations. Nature Cancer. https://doi.org/10.1038/s43018-020-0087-6
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.