Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images

We proposed a highly versatile two-step transfer learning pipeline for predicting the gene signature defining the intrinsic breast cancer subtypes using unannotated pathological images. Deciphering breast cancer molecular subtypes by deep learning approaches could provide a convenient and efficient...

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Autores principales: Nam Nhut Phan, Chi-Cheng Huang, Ling-Ming Tseng, Eric Y. Chuang
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/5fd822eabb5f4ec8b5c3953244c24d43
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spelling oai:doaj.org-article:5fd822eabb5f4ec8b5c3953244c24d432021-12-01T22:31:09ZPredicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images2234-943X10.3389/fonc.2021.769447https://doaj.org/article/5fd822eabb5f4ec8b5c3953244c24d432021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.769447/fullhttps://doaj.org/toc/2234-943XWe proposed a highly versatile two-step transfer learning pipeline for predicting the gene signature defining the intrinsic breast cancer subtypes using unannotated pathological images. Deciphering breast cancer molecular subtypes by deep learning approaches could provide a convenient and efficient method for the diagnosis of breast cancer patients. It could reduce costs associated with transcriptional profiling and subtyping discrepancy between IHC assays and mRNA expression. Four pretrained models such as VGG16, ResNet50, ResNet101, and Xception were trained with our in-house pathological images from breast cancer patient with recurrent status in the first transfer learning step and TCGA-BRCA dataset for the second transfer learning step. Furthermore, we also trained ResNet101 model with weight from ImageNet for comparison to the aforementioned models. The two-step deep learning models showed promising classification results of the four breast cancer intrinsic subtypes with accuracy ranging from 0.68 (ResNet50) to 0.78 (ResNet101) in both validation and testing sets. Additionally, the overall accuracy of slide-wise prediction showed even higher average accuracy of 0.913 with ResNet101 model. The micro- and macro-average area under the curve (AUC) for these models ranged from 0.88 (ResNet50) to 0.94 (ResNet101), whereas ResNet101_imgnet weighted with ImageNet archived an AUC of 0.92. We also show the deep learning model prediction performance is significantly improved relatively to the common Genefu tool for breast cancer classification. Our study demonstrated the capability of deep learning models to classify breast cancer intrinsic subtypes without the region of interest annotation, which will facilitate the clinical applicability of the proposed models.Nam Nhut PhanNam Nhut PhanNam Nhut PhanChi-Cheng HuangChi-Cheng HuangLing-Ming TsengLing-Ming TsengEric Y. ChuangEric Y. ChuangEric Y. ChuangFrontiers Media S.A.articledeep learningconvolutional neural networksbreast cancer intrinsic subtypespathologywhole slide imagePAM50Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic deep learning
convolutional neural networks
breast cancer intrinsic subtypes
pathology
whole slide image
PAM50
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle deep learning
convolutional neural networks
breast cancer intrinsic subtypes
pathology
whole slide image
PAM50
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Nam Nhut Phan
Nam Nhut Phan
Nam Nhut Phan
Chi-Cheng Huang
Chi-Cheng Huang
Ling-Ming Tseng
Ling-Ming Tseng
Eric Y. Chuang
Eric Y. Chuang
Eric Y. Chuang
Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
description We proposed a highly versatile two-step transfer learning pipeline for predicting the gene signature defining the intrinsic breast cancer subtypes using unannotated pathological images. Deciphering breast cancer molecular subtypes by deep learning approaches could provide a convenient and efficient method for the diagnosis of breast cancer patients. It could reduce costs associated with transcriptional profiling and subtyping discrepancy between IHC assays and mRNA expression. Four pretrained models such as VGG16, ResNet50, ResNet101, and Xception were trained with our in-house pathological images from breast cancer patient with recurrent status in the first transfer learning step and TCGA-BRCA dataset for the second transfer learning step. Furthermore, we also trained ResNet101 model with weight from ImageNet for comparison to the aforementioned models. The two-step deep learning models showed promising classification results of the four breast cancer intrinsic subtypes with accuracy ranging from 0.68 (ResNet50) to 0.78 (ResNet101) in both validation and testing sets. Additionally, the overall accuracy of slide-wise prediction showed even higher average accuracy of 0.913 with ResNet101 model. The micro- and macro-average area under the curve (AUC) for these models ranged from 0.88 (ResNet50) to 0.94 (ResNet101), whereas ResNet101_imgnet weighted with ImageNet archived an AUC of 0.92. We also show the deep learning model prediction performance is significantly improved relatively to the common Genefu tool for breast cancer classification. Our study demonstrated the capability of deep learning models to classify breast cancer intrinsic subtypes without the region of interest annotation, which will facilitate the clinical applicability of the proposed models.
format article
author Nam Nhut Phan
Nam Nhut Phan
Nam Nhut Phan
Chi-Cheng Huang
Chi-Cheng Huang
Ling-Ming Tseng
Ling-Ming Tseng
Eric Y. Chuang
Eric Y. Chuang
Eric Y. Chuang
author_facet Nam Nhut Phan
Nam Nhut Phan
Nam Nhut Phan
Chi-Cheng Huang
Chi-Cheng Huang
Ling-Ming Tseng
Ling-Ming Tseng
Eric Y. Chuang
Eric Y. Chuang
Eric Y. Chuang
author_sort Nam Nhut Phan
title Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
title_short Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
title_full Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
title_fullStr Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
title_full_unstemmed Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images
title_sort predicting breast cancer gene expression signature by applying deep convolutional neural networks from unannotated pathological images
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/5fd822eabb5f4ec8b5c3953244c24d43
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