Plasma proteomic profiles predict individual future health risk
Abstract Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43575-7 |
| _version_ | 1797414572082069504 |
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| author | Jia You Yu Guo Yi Zhang Ju-Jiao Kang Lin-Bo Wang Jian-Feng Feng Wei Cheng Jin-Tai Yu |
| author_facet | Jia You Yu Guo Yi Zhang Ju-Jiao Kang Lin-Bo Wang Jian-Feng Feng Wei Cheng Jin-Tai Yu |
| author_sort | Jia You |
| collection | DOAJ |
| description | Abstract Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings. |
| first_indexed | 2024-03-09T05:35:19Z |
| format | Article |
| id | doaj.art-2ac12b2207334761b365d93cd61c20af |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T05:35:19Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2ac12b2207334761b365d93cd61c20af2023-12-03T12:28:42ZengNature PortfolioNature Communications2041-17232023-11-0114111310.1038/s41467-023-43575-7Plasma proteomic profiles predict individual future health riskJia You0Yu Guo1Yi Zhang2Ju-Jiao Kang3Lin-Bo Wang4Jian-Feng Feng5Wei Cheng6Jin-Tai Yu7Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, Institute of Science and Technology for Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityAbstract Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings.https://doi.org/10.1038/s41467-023-43575-7 |
| spellingShingle | Jia You Yu Guo Yi Zhang Ju-Jiao Kang Lin-Bo Wang Jian-Feng Feng Wei Cheng Jin-Tai Yu Plasma proteomic profiles predict individual future health risk Nature Communications |
| title | Plasma proteomic profiles predict individual future health risk |
| title_full | Plasma proteomic profiles predict individual future health risk |
| title_fullStr | Plasma proteomic profiles predict individual future health risk |
| title_full_unstemmed | Plasma proteomic profiles predict individual future health risk |
| title_short | Plasma proteomic profiles predict individual future health risk |
| title_sort | plasma proteomic profiles predict individual future health risk |
| url | https://doi.org/10.1038/s41467-023-43575-7 |
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