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Plasma protein patterns as comprehensive indicators of health.
Nature Medicine ( IF 82.9 ) Pub Date : 2019-12-02 , DOI: 10.1038/s41591-019-0665-2
Stephen A Williams 1 , Mika Kivimaki 2 , Claudia Langenberg 3 , Aroon D Hingorani 4, 5, 6 , J P Casas 7 , Claude Bouchard 8 , Christian Jonasson 9 , Mark A Sarzynski 10 , Martin J Shipley 2 , Leigh Alexander 1 , Jessica Ash 1 , Tim Bauer 1 , Jessica Chadwick 1 , Gargi Datta 1 , Robert Kirk DeLisle 1 , Yolanda Hagar 1 , Michael Hinterberg 1 , Rachel Ostroff 1 , Sophie Weiss 1 , Peter Ganz 11 , Nicholas J Wareham 3
Affiliation  

Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.

中文翻译:

血浆蛋白模式作为健康的综合指标。

蛋白质是介导基因功能 1,2 并调节合并症 3-10、行为和药物治疗 11 的效应分子。它们代表了个性化、系统和数据驱动的诊断、预防、监测和治疗的巨大潜在资源。然而,使用血浆蛋白同时对多种健康状况进行个体化健康评估的概念尚未经过测试。在这里,我们表明血浆蛋白表达模式强烈编码多种不同的健康状态、未来的疾病风险和生活方式行为。我们针对 11 种不同的健康指标开发并验证了蛋白质表型模型:肝脏脂肪、肾脏过滤、体脂百分比、内脏脂肪量、瘦体重、心肺健康、体力活动、饮酒、吸烟、糖尿病风险和原发性心血管事件风险。这些分析是对存档样本和临床数据进行前瞻性计划、记录和大规模执行的,在 16,894 名参与者中总共进行了约 8500 万次蛋白质测量。我们的概念验证研究表明,蛋白质表达模式可靠地编码了许多不同的健康问题,并且大规模蛋白质扫描 12-16 与机器学习相结合对于开发和未来同时提供多种健康措施是可行的。我们预计,通过进一步验证和添加更多蛋白质表型模型,这种方法可以实现单一来源、个性化的所谓液体健康检查。在 16,894 名参与者中总共进行了约 8500 万次蛋白质测量。我们的概念验证研究表明,蛋白质表达模式可靠地编码了许多不同的健康问题,并且大规模蛋白质扫描 12-16 与机器学习相结合对于开发和未来同时提供多种健康措施是可行的。我们预计,通过进一步验证和添加更多蛋白质表型模型,这种方法可以实现单一来源、个性化的所谓液体健康检查。在 16,894 名参与者中总共进行了约 8500 万次蛋白质测量。我们的概念验证研究表明,蛋白质表达模式可靠地编码了许多不同的健康问题,并且大规模蛋白质扫描 12-16 与机器学习相结合对于开发和未来同时提供多种健康措施是可行的。我们预计,通过进一步验证和添加更多蛋白质表型模型,这种方法可以实现单一来源、个性化的所谓液体健康检查。大规模蛋白质扫描12-16 与机器学习相结合,对于开发和未来同时提供多种健康措施是可行的。我们预计,通过进一步验证和添加更多蛋白质表型模型,这种方法可以实现单一来源、个性化的所谓液体健康检查。大规模蛋白质扫描12-16 与机器学习相结合,对于开发和未来同时提供多种健康措施是可行的。我们预计,通过进一步验证和添加更多蛋白质表型模型,这种方法可以实现单一来源、个性化的所谓液体健康检查。
更新日期:2019-12-02
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