The Library
Development and validation of a weakly supervised deep learning framework to predict the status of molecular pathways and key mutations in colorectal cancer from routine histology images : a retrospective study
Tools
Tools
Tools
Bilal, Mohsin, Raza, Shan-e-Ahmed, Azam, Ayesha, Graham, Simon, Ilyas, Mohammad, Cree, Ian A., Snead, David, Minhas, Fayyaz ul Amir Afsar and Rajpoot, Nasir M. (2021) Development and validation of a weakly supervised deep learning framework to predict the status of molecular pathways and key mutations in colorectal cancer from routine histology images : a retrospective study. The Lancet Digital Health, 3 (12). e763-e772. doi:10.1016/S2589-7500(21)00180-1 ISSN 2589-7500.
|
PDF
WRAP-development-validation-weakly-supervised-deep-learning-framework-Rajpoot-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (1496Kb) | Preview |
Official URL: https://doi.org/10.1016/S2589-7500(21)00180-1
Abstract
Background:
Determining the status of molecular pathways and key mutations in colorectal cancer is crucial for optimal therapeutic decision making. We therefore aimed to develop a novel deep learning pipeline to predict the status of key molecular pathways and mutations from whole-slide images of haematoxylin and eosin-stained colorectal cancer slides as an alternative to current tests.
Methods:
In this retrospective study, we used 502 diagnostic slides of primary colorectal tumours from 499 patients in The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) cohort and developed a weakly supervised deep learning framework involving three separate convolutional neural network models. Whole-slide images were divided into equally sized tiles and model 1 (ResNet18) extracted tumour tiles from non-tumour tiles. These tumour tiles were inputted into model 2 (adapted ResNet34), trained by iterative draw and rank sampling to calculate a prediction score for each tile that represented the likelihood of a tile belonging to the molecular labels of high mutation density (vs low mutation density), microsatellite instability (vs microsatellite stability), chromosomal instability (vs genomic stability), CpG island methylator phenotype (CIMP)-high (vs CIMP-low), BRAFmut (vs BRAFWT), TP53mut (vs TP53WT), and KRASWT (vs KRASmut). These scores were used to identify the top-ranked titles from each slide, and model 3 (HoVer-Net) segmented and classified the different types of cell nuclei in these tiles. We calculated the area under the convex hull of the receiver operating characteristic curve (AUROC) as a model performance measure and compared our results with those of previously published methods.
Findings:
Our iterative draw and rank sampling method yielded mean AUROCs for the prediction of hypermutation (0·81 [SD 0·03] vs 0·71), microsatellite instability (0·86 [0·04] vs 0·74), chromosomal instability (0·83 [0·02] vs 0·73), BRAFmut (0·79 [0·01] vs 0·66), and TP53mut (0·73 [0·02] vs 0·64) in the TCGA-CRC-DX cohort that were higher than those from previously published methods, and an AUROC for KRASmut that was similar to previously reported methods (0·60 [SD 0·04] vs 0·60). Mean AUROC for predicting CIMP-high status was 0·79 (SD 0·05). We found high proportions of tumour-infiltrating lymphocytes and necrotic tumour cells to be associated with microsatellite instability, and high proportions of tumour-infiltrating lymphocytes and a low proportion of necrotic tumour cells to be associated with hypermutation.
Interpretation:
After large-scale validation, our proposed algorithm for predicting clinically important mutations and molecular pathways, such as microsatellite instability, in colorectal cancer could be used to stratify patients for targeted therapies with potentially lower costs and quicker turnaround times than sequencing-based or immunohistochemistry-based approaches.
Funding:
The UK Medical Research Council.
| Item Type: | Journal Article | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | |||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Computer Science | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Colon (Anatomy) -- Cancer -- Molecular aspects, Rectum -- Cancer -- Molecular aspects, Colon (Anatomy) -- Cancer -- Research | |||||||||
| Journal or Publication Title: | The Lancet Digital Health | |||||||||
| Publisher: | Elsevier Inc. | |||||||||
| ISSN: | 2589-7500 | |||||||||
| Official Date: | 1 December 2021 | |||||||||
| Dates: |
|
|||||||||
| Volume: | 3 | |||||||||
| Number: | 12 | |||||||||
| Page Range: | e763-e772 | |||||||||
| DOI: | 10.1016/S2589-7500(21)00180-1 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 8 November 2021 | |||||||||
| Date of first compliant Open Access: | 9 November 2021 | |||||||||
| RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
