Artificial intelligence defines protein-based classification of thyroid nodules

Abstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-emb...

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Main Authors: Yaoting Sun, Sathiyamoorthy Selvarajan, Zelin Zang, Wei Liu, Yi Zhu, Hao Zhang, Wanyuan Chen, Hao Chen, Lu Li, Xue Cai, Huanhuan Gao, Zhicheng Wu, Yongfu Zhao, Lirong Chen, Xiaodong Teng, Sangeeta Mantoo, Tony Kiat-Hon Lim, Bhuvaneswari Hariraman, Serene Yeow, Syed Muhammad Fahmy Alkaff, Sze Sing Lee, Guan Ruan, Qiushi Zhang, Tiansheng Zhu, Yifan Hu, Zhen Dong, Weigang Ge, Qi Xiao, Weibin Wang, Guangzhi Wang, Junhong Xiao, Yi He, Zhihong Wang, Wei Sun, Yuan Qin, Jiang Zhu, Xu Zheng, Linyan Wang, Xi Zheng, Kailun Xu, Yingkuan Shao, Shu Zheng, Kexin Liu, Ruedi Aebersold, Haixia Guan, Xiaohong Wu, Dingcun Luo, Wen Tian, Stan Ziqing Li, Oi Lian Kon, Narayanan Gopalakrishna Iyer, Tiannan Guo
Format: Article
Language:English
Published: Nature Publishing Group 2022-09-01
Series:Cell Discovery
Online Access:https://doi.org/10.1038/s41421-022-00442-x
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author Yaoting Sun
Sathiyamoorthy Selvarajan
Zelin Zang
Wei Liu
Yi Zhu
Hao Zhang
Wanyuan Chen
Hao Chen
Lu Li
Xue Cai
Huanhuan Gao
Zhicheng Wu
Yongfu Zhao
Lirong Chen
Xiaodong Teng
Sangeeta Mantoo
Tony Kiat-Hon Lim
Bhuvaneswari Hariraman
Serene Yeow
Syed Muhammad Fahmy Alkaff
Sze Sing Lee
Guan Ruan
Qiushi Zhang
Tiansheng Zhu
Yifan Hu
Zhen Dong
Weigang Ge
Qi Xiao
Weibin Wang
Guangzhi Wang
Junhong Xiao
Yi He
Zhihong Wang
Wei Sun
Yuan Qin
Jiang Zhu
Xu Zheng
Linyan Wang
Xi Zheng
Kailun Xu
Yingkuan Shao
Shu Zheng
Kexin Liu
Ruedi Aebersold
Haixia Guan
Xiaohong Wu
Dingcun Luo
Wen Tian
Stan Ziqing Li
Oi Lian Kon
Narayanan Gopalakrishna Iyer
Tiannan Guo
author_facet Yaoting Sun
Sathiyamoorthy Selvarajan
Zelin Zang
Wei Liu
Yi Zhu
Hao Zhang
Wanyuan Chen
Hao Chen
Lu Li
Xue Cai
Huanhuan Gao
Zhicheng Wu
Yongfu Zhao
Lirong Chen
Xiaodong Teng
Sangeeta Mantoo
Tony Kiat-Hon Lim
Bhuvaneswari Hariraman
Serene Yeow
Syed Muhammad Fahmy Alkaff
Sze Sing Lee
Guan Ruan
Qiushi Zhang
Tiansheng Zhu
Yifan Hu
Zhen Dong
Weigang Ge
Qi Xiao
Weibin Wang
Guangzhi Wang
Junhong Xiao
Yi He
Zhihong Wang
Wei Sun
Yuan Qin
Jiang Zhu
Xu Zheng
Linyan Wang
Xi Zheng
Kailun Xu
Yingkuan Shao
Shu Zheng
Kexin Liu
Ruedi Aebersold
Haixia Guan
Xiaohong Wu
Dingcun Luo
Wen Tian
Stan Ziqing Li
Oi Lian Kon
Narayanan Gopalakrishna Iyer
Tiannan Guo
author_sort Yaoting Sun
collection DOAJ
description Abstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.
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spelling doaj.art-dc770d52b9e6450fbc48a100893456d62022-12-22T01:44:45ZengNature Publishing GroupCell Discovery2056-59682022-09-018111710.1038/s41421-022-00442-xArtificial intelligence defines protein-based classification of thyroid nodulesYaoting Sun0Sathiyamoorthy Selvarajan1Zelin Zang2Wei Liu3Yi Zhu4Hao Zhang5Wanyuan Chen6Hao Chen7Lu Li8Xue Cai9Huanhuan Gao10Zhicheng Wu11Yongfu Zhao12Lirong Chen13Xiaodong Teng14Sangeeta Mantoo15Tony Kiat-Hon Lim16Bhuvaneswari Hariraman17Serene Yeow18Syed Muhammad Fahmy Alkaff19Sze Sing Lee20Guan Ruan21Qiushi Zhang22Tiansheng Zhu23Yifan Hu24Zhen Dong25Weigang Ge26Qi Xiao27Weibin Wang28Guangzhi Wang29Junhong Xiao30Yi He31Zhihong Wang32Wei Sun33Yuan Qin34Jiang Zhu35Xu Zheng36Linyan Wang37Xi Zheng38Kailun Xu39Yingkuan Shao40Shu Zheng41Kexin Liu42Ruedi Aebersold43Haixia Guan44Xiaohong Wu45Dingcun Luo46Wen Tian47Stan Ziqing Li48Oi Lian Kon49Narayanan Gopalakrishna Iyer50Tiannan Guo51Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityDepartment of Anatomical Pathology, Division of Pathology, Singapore General HospitalSchool of Engineering, Westlake UniversityWestlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityDepartment of Thyroid Surgery, the First Hospital of China Medical UniversityCancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeWestlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityDepartment of General Surgery, The Second Hospital of Dalian Medical UniversityDepartment of Pathology, The Second Affiliated Hospital of College of Medicine, Zhejiang UniversityDepartment of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Anatomical Pathology, Division of Pathology, Singapore General HospitalDepartment of Anatomical Pathology, Division of Pathology, Singapore General HospitalDepartment of Head and Neck Surgery, National Cancer Center SingaporeDivision of Medical Sciences, National Cancer Center SingaporeDepartment of Anatomical Pathology, Division of Pathology, Singapore General HospitalDivision of Medical Sciences, National Cancer Center SingaporeWestlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityWestlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityWestlake Omics (Hangzhou) Biotechnology Co., Ltd.Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityDepartment of Surgical Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of General Surgery, The Second Hospital of Dalian Medical UniversityDepartment of General Surgery, The Second Hospital of Dalian Medical UniversityDepartment of Urology, The Second Hospital of Dalian Medical UniversityDepartment of Thyroid Surgery, the First Hospital of China Medical UniversityDepartment of Thyroid Surgery, the First Hospital of China Medical UniversityDepartment of Thyroid Surgery, the First Hospital of China Medical UniversityDepartment of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical UniversityDepartment of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of MedicineCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang, China), The Second Affiliated Hospital, Zhejiang University School of MedicineCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang, China), The Second Affiliated Hospital, Zhejiang University School of MedicineCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang, China), The Second Affiliated Hospital, Zhejiang University School of MedicineCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang, China), The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Clinical Pharmacology, College of Pharmacy, Dalian Medical UniversityDepartment of Biology, Institute of Molecular Systems Biology, ETH ZurichDepartment of Endocrinology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s HospitalDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of MedicineDepartment of General Surgery, PLA General HospitalSchool of Engineering, Westlake UniversityDivision of Medical Sciences, National Cancer Center SingaporeDepartment of Head and Neck Surgery, National Cancer Center SingaporeWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake UniversityAbstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.https://doi.org/10.1038/s41421-022-00442-x
spellingShingle Yaoting Sun
Sathiyamoorthy Selvarajan
Zelin Zang
Wei Liu
Yi Zhu
Hao Zhang
Wanyuan Chen
Hao Chen
Lu Li
Xue Cai
Huanhuan Gao
Zhicheng Wu
Yongfu Zhao
Lirong Chen
Xiaodong Teng
Sangeeta Mantoo
Tony Kiat-Hon Lim
Bhuvaneswari Hariraman
Serene Yeow
Syed Muhammad Fahmy Alkaff
Sze Sing Lee
Guan Ruan
Qiushi Zhang
Tiansheng Zhu
Yifan Hu
Zhen Dong
Weigang Ge
Qi Xiao
Weibin Wang
Guangzhi Wang
Junhong Xiao
Yi He
Zhihong Wang
Wei Sun
Yuan Qin
Jiang Zhu
Xu Zheng
Linyan Wang
Xi Zheng
Kailun Xu
Yingkuan Shao
Shu Zheng
Kexin Liu
Ruedi Aebersold
Haixia Guan
Xiaohong Wu
Dingcun Luo
Wen Tian
Stan Ziqing Li
Oi Lian Kon
Narayanan Gopalakrishna Iyer
Tiannan Guo
Artificial intelligence defines protein-based classification of thyroid nodules
Cell Discovery
title Artificial intelligence defines protein-based classification of thyroid nodules
title_full Artificial intelligence defines protein-based classification of thyroid nodules
title_fullStr Artificial intelligence defines protein-based classification of thyroid nodules
title_full_unstemmed Artificial intelligence defines protein-based classification of thyroid nodules
title_short Artificial intelligence defines protein-based classification of thyroid nodules
title_sort artificial intelligence defines protein based classification of thyroid nodules
url https://doi.org/10.1038/s41421-022-00442-x
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