ArticleCell discovery2022
Artificial intelligence defines protein-based classification of thyroid nodules.
Erratum issuedOpen access · goldAbstract read
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Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
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38citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
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38 citing papers in PubMed, 71 citations in OpenAlex.
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- Proteomic analysis reveals modulation of key proteins in follicular thyroid cancer progression.Chinese medical journal · 2026Article
- Proteogenomic characterization delineates clinically relevant subtypes of advanced differentiated thyroid cancer.Cell reports. Medicine · 2026Article
- A targeted proteomics assay for the preoperative diagnosis of thyroid nodules.Cell reports. Medicine · 2026Article
- ProteoAutoNet: high-throughput co-eluted protein analysis with robotics and machine learning.Nature communications · 2026Article
- Multi-center multi-omics integration predicts individualized prognosis in medullary thyroid carcinoma.Nature communications · 2026Article
- The role of artificial intelligence in thyroid cytology of indeterminate nodules: from digital cytology to multimodal precision triage.Frontiers in endocrinology · 2026Review
- A deep learning model for multiclass lung cancer classification using multimodal data fusion.Discover oncology · 2025Article
- Predicting and Treating Pulmonary Fibrosis with Proteomic Biomarker Investigations.Biomedicines · 2025Review
- Proteomic Profiling of EUS-FNA Samples Differentiates Pancreatic Adenocarcinoma from Mass-Forming Chronic Pancreatitis.Biomedicines · 2025Article
- Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules.Endocrinology and metabolism (Seoul, Korea) · 2025Article
- Towards an Integrated Multi-Omic Approach to Improve the Diagnostic Accuracy of Fine-Needle Aspiration in Thyroid Nodules with Indeterminate Cytology.Diagnostics (Basel, Switzerland) · 2025Review
- Artificial intelligence utilization in cancer screening program across ASEAN: a scoping review.BMC cancer · 2025Article
- Advancements in proteogenomics for preclinical targeted cancer therapy research.Biophysics reports · 2025Article
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- iDIA-QC: AI-empowered data-independent acquisition mass spectrometry-based quality control.Nature communications · 2025Article
- DiffBP: generative diffusion of 3D molecules for target protein binding.Chemical science · 2025Article
- Comparative urine proteomic study involving papillary thyroid carcinoma and benign thyroid nodules.Frontiers in oncology · 2025Article
- Towards routine proteome profiling of FFPE tissue: insights from a 1,220-case pan-cancer study.The EMBO journal · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
52 authors at 14 institutions in 3 countries.
Yaoting Sun *Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-7613-648X
Sathiyamoorthy Selvarajan *Department of Anatomical Pathology, Division of Pathology, Singapore General Hospital, Singapore, Singapore.
Zelin Zang *School of Engineering, Westlake University, No.18 Shilongshan Road, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0003-2831-5437
Wei Liu *Westlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Yi Zhu *Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0003-0429-0802
Hao Zhang *Department of Thyroid Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Wanyuan ChenCancer Center, Department of Pathology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Hao ChenWestlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Lu LiWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Xue CaiWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Huanhuan GaoWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Zhicheng WuWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Yongfu ZhaoDepartment of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Lirong ChenDepartment of Pathology, The Second Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xiaodong TengDepartment of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Sangeeta MantooDepartment of Anatomical Pathology, Division of Pathology, Singapore General Hospital, Singapore, Singapore.
Tony Kiat-Hon LimDepartment of Anatomical Pathology, Division of Pathology, Singapore General Hospital, Singapore, Singapore.
Bhuvaneswari HariramanDepartment of Head and Neck Surgery, National Cancer Center Singapore, Singapore, Singapore.
Serene YeowDivision of Medical Sciences, National Cancer Center Singapore, Singapore, Singapore.
Syed Muhammad Fahmy AlkaffDepartment of Anatomical Pathology, Division of Pathology, Singapore General Hospital, Singapore, Singapore.
Sze Sing LeeDivision of Medical Sciences, National Cancer Center Singapore, Singapore, Singapore.
Guan RuanWestlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Qiushi ZhangWestlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Tiansheng ZhuWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Yifan HuWestlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Zhen DongWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-3480-3421
Weigang GeWestlake Omics (Hangzhou) Biotechnology Co., Ltd., No.1 Yunmeng Road, Hangzhou, Zhejiang, China.
Qi XiaoWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Weibin WangDepartment of Surgical Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Guangzhi WangDepartment of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Junhong XiaoDepartment of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Yi HeDepartment of Urology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Zhihong WangDepartment of Thyroid Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Wei SunDepartment of Thyroid Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Yuan QinDepartment of Thyroid Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Jiang ZhuDepartment of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Xu ZhengLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.
Linyan WangDepartment of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Xi ZhengCancer 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 Medicine, Hangzhou, Zhejiang, China.
Kailun XuCancer 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 Medicine, Hangzhou, Zhejiang, China.
Yingkuan ShaoCancer 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 Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-9683-5691
Shu ZhengCancer 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 Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-2521-190X
Kexin LiuDepartment of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.
Ruedi AebersoldDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-9576-3267
Haixia GuanDepartment of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Xiaohong WuDepartment of Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou, Zhejiang, China.
Dingcun LuoDepartment of Surgical Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Wen TianDepartment of General Surgery, PLA General Hospital, Beijing, China.
Stan Ziqing LiSchool of Engineering, Westlake University, No.18 Shilongshan Road, Hangzhou, Zhejiang, China. Stan.ZQ.Li@westlake.edu.cn.ORCID http://orcid.org/0000-0002-2961-8096
Oi Lian KonDivision of Medical Sciences, National Cancer Center Singapore, Singapore, Singapore. kairos712@singnet.com.sg.
Narayanan Gopalakrishna IyerDepartment of Head and Neck Surgery, National Cancer Center Singapore, Singapore, Singapore. gmsngi@nus.edu.sg.ORCID http://orcid.org/0000-0002-8812-6219
Tiannan GuoWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. guotiannan@westlake.edu.cn.ORCID http://orcid.org/0000-0003-3869-7651
Westlake University · CNDalian Medical University · CNZhejiang University · CNFirst Hospital of China Medical University · CNNational Cancer Centre Singapore · SGSingapore General Hospital · SGSecond Affiliated Hospital of Zhejiang University · CNZhejiang Provincial People's Hospital · CNChinese PLA General Hospital · CNGuangdong Academy of Medical Sciences · CNHangzhou First People's Hospital · CNSingHealth · SGSir Run Run Shaw Hospital · CNUniversity of Zurich · CH
Funding
National Natural Science Foundation of China (National Science Foundation of China) 81972492
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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