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Exposomics: perfection not required. Exposomics: 不要求完美。
Pub Date : 2024-10-04 eCollection Date: 2024-01-01 DOI: 10.1093/exposome/osae006
Gary W Miller
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引用次数: 0
A long and winding road: Culture change on data sharing in exposomics 漫长而曲折的道路:世卫组织数据共享的文化变革
Pub Date : 2024-04-13 DOI: 10.1093/exposome/osae004
Robert O Wright, Konstantinos C Makris, P. Natsiavas, Timothy Fennel, Blake R Rushing, Ander Wilson
Data sharing requires cooperation from data generators (e.g., epidemiologists, lab investigators) and data users (e.g., epidemiologists, biostatisticians, computer scientists). Data generation and data use in human exposome studies require significant but different skill sets and are separated temporally in many cases. Sharing will require maintaining a history of data generation and a system to address the concerns of data generators around credit for conducting rigorous work (e.g., authorship). Sharing also requires addressing the needs of data users to facilitate harmonization, searchability and QA/QC of data. We present these issues from the perspectives of data generators and data users and include the special case of real-world data (e.g., electronic health records). We conclude with recommendations to address how to better promote data sharing in exposomics through authorship, cost recovery and addressing ethical issues.
数据共享需要数据生成者(如流行病学家、实验室研究人员)和数据使用者(如流行病学家、生物统计学家、计算机科学家)的合作。人类暴露组研究中的数据生成和数据使用需要大量不同的技能组合,而且在许多情况下时间上是分离的。要实现共享,就必须保留数据生成的历史记录,并建立一个系统来解决数据生成者对开展严谨工作所获得的荣誉(如作者身份)的担忧。共享还需要满足数据用户的需求,以促进数据的统一、可搜索性和质量保证/质量控制。我们从数据生成者和数据使用者的角度来阐述这些问题,并包括真实世界数据(如电子健康记录)的特殊情况。最后,我们就如何通过作者身份、成本回收和解决伦理问题更好地促进暴露组学中的数据共享提出了建议。
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引用次数: 0
Interactive data sharing for multiple questionnaire-based exposome-wide association studies and exposome correlations in the Personalized Environment and Genes Study. 个性化环境与基因研究中基于多份问卷的暴露组关联研究和暴露组相关性的交互式数据共享。
Pub Date : 2024-02-12 eCollection Date: 2024-01-01 DOI: 10.1093/exposome/osae003
Dillon Lloyd, John S House, Farida S Akhtari, Charles P Schmitt, David C Fargo, Elizabeth H Scholl, Jason Phillips, Shail Choksi, Ruchir Shah, Janet E Hall, Alison A Motsinger-Reif

The correlations among individual exposures in the exposome, which refers to all exposures an individual encounters throughout life, are important for understanding the landscape of how exposures co-occur, and how this impacts health and disease. Exposome-wide association studies (ExWAS), which are analogous to genome-wide association studies (GWAS), are increasingly being used to elucidate links between the exposome and disease. Despite increased interest in the exposome, tools and publications that characterize exposure correlations and their relationships with human disease are limited, and there is a lack of data and results sharing in resources like the GWAS catalog. To address these gaps, we developed the PEGS Explorer web application to explore exposure correlations in data from the diverse North Carolina-based Personalized Environment and Genes Study (PEGS) that were rigorously calculated to account for differing data types and previously published results from ExWAS. Through globe visualizations, PEGS Explorer allows users to explore correlations between exposures found to be associated with complex diseases. The exposome data used for analysis includes not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The web application addresses the lack of accessible data and results sharing, a major challenge in the field, and enables users to put results in context, generate hypotheses, and, importantly, replicate findings in other cohorts. PEGS Explorer will be updated with additional results as they become available, ensuring it is an up-to-date resource in exposome science.

暴露组是指个体一生中接触到的所有暴露,暴露组中个体暴露之间的相关性对于了解暴露如何共存以及如何影响健康和疾病非常重要。全暴露体关联研究(ExWAS)类似于全基因组关联研究(GWAS),越来越多地被用于阐明暴露体与疾病之间的联系。尽管人们对暴露组的兴趣与日俱增,但描述暴露相关性及其与人类疾病关系的工具和出版物却十分有限,而且缺乏像 GWAS 目录这样的数据和结果共享资源。为了填补这些空白,我们开发了 PEGS Explorer 网络应用程序,以探索来自北卡罗来纳州个性化环境与基因研究(PEGS)的各种数据中的暴露相关性,这些数据经过严格计算,考虑到了不同的数据类型和以前发表的 ExWAS 结果。通过全球可视化,PEGS Explorer 允许用户探索发现与复杂疾病相关的暴露之间的相关性。用于分析的暴露组数据不仅包括点源污染和臭氧水平等标准环境暴露,还包括饮食、药物、生活方式因素、压力和职业等暴露。该网络应用程序解决了该领域面临的主要挑战--缺乏可访问的数据和结果共享的问题,使用户能够将结果置于上下文中,提出假设,更重要的是,在其他队列中复制研究结果。PEGS Explorer 将在有更多结果时及时更新,确保它成为暴露组科学的最新资源。
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引用次数: 0
Questionnaire-based exposome-wide association studies for common diseases in the Personalized Environment and Genes Study. 在个性化环境与基因研究中,对常见疾病进行基于问卷的全暴露关联研究。
Pub Date : 2024-02-12 eCollection Date: 2024-01-01 DOI: 10.1093/exposome/osae002
Dillon Lloyd, John S House, Farida S Akhtari, Charles P Schmitt, David C Fargo, Elizabeth H Scholl, Jason Phillips, Shail Choksi, Ruchir Shah, Janet E Hall, Alison A Motsinger-Reif

The exposome collectively refers to all exposures, beginning in utero and continuing throughout life, and comprises not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The exposome interacts with individual genetic and epigenetic characteristics to affect human health and disease, but large-scale studies that characterize the exposome and its relationships with human disease are limited. To address this gap, we used extensive questionnaire data from the diverse North Carolina-based Personalized Environment and Genes Study (PEGS, n = 9, 429) to evaluate exposure associations in relation to common diseases. We performed an exposome-wide association study (ExWAS) to examine single exposure models and their associations with 11 common complex diseases, namely allergic rhinitis, asthma, bone loss, fibroids, high cholesterol, hypertension, iron-deficient anemia, ovarian cysts, lower GI polyps, migraines, and type 2 diabetes. Across diseases, we found associations with lifestyle factors and socioeconomic status as well as asbestos, various dust types, biohazardous material, and textile-related exposures. We also found disease-specific associations such as fishing with lead weights and migraines. To differentiate between a replicated result and a novel finding, we used an AI-based literature search and database tool that allowed us to examine the current literature. We found both replicated findings, especially for lifestyle factors such as sleep and smoking across diseases, and novel findings, especially for occupational exposures and multiple diseases.

暴露体是指从子宫内开始并持续一生的所有暴露,不仅包括点源污染和臭氧水平等标准环境暴露,还包括饮食、药物、生活方式因素、压力和职业等暴露。暴露组与个体遗传和表观遗传特征相互作用,影响人类健康和疾病,但描述暴露组特征及其与人类疾病关系的大规模研究非常有限。为了填补这一空白,我们使用了来自北卡罗来纳州个性化环境与基因研究(PEGS,n = 9,429)的大量问卷数据,以评估暴露与常见疾病的关系。我们进行了一项全暴露体关联研究(ExWAS),研究了单一暴露模型及其与 11 种常见复杂疾病的关联,即过敏性鼻炎、哮喘、骨质疏松、子宫肌瘤、高胆固醇、高血压、缺铁性贫血、卵巢囊肿、下消化道息肉、偏头痛和 2 型糖尿病。在各种疾病中,我们发现与生活方式因素、社会经济地位以及石棉、各种粉尘、生物危险材料和纺织品相关接触有关。我们还发现了与特定疾病的关联,如钓鱼与铅重和偏头痛。为了区分重复结果和新发现,我们使用了一种基于人工智能的文献搜索和数据库工具,该工具允许我们检查当前的文献。我们既发现了重复结果,尤其是睡眠和吸烟等生活方式因素与不同疾病的关系,也发现了新发现,尤其是职业暴露与多种疾病的关系。
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引用次数: 0
Decoding the exposome: Data science methodologies and implications in Exposome-Wide association studies (ExWASs) 解码暴露组:全暴露组关联研究(ExWASs)中的数据科学方法及其影响
Pub Date : 2024-01-17 DOI: 10.1093/exposome/osae001
Ming Kei Chung, John S. House, F. Akhtari, Konstantinos C Makris, Michael A. Langston, Khandaker Talat Islam, Philip Holmes, Marc Chadeau-Hyam, Alex I Smirnov, Xiuxia Du, Anne E Thessen, Yuxia Cui, Kai Zhang, Arjun K. Manrai, Alison Motsinger-Reif, Chirag J Patel
This paper explores the exposome concept and its role in elucidating the interplay between environmental exposures and human health. We introduce two key concepts critical for exposomics research. Firstly, we discuss the joint impact of genetics and environment on phenotypes, emphasizing the variance attributable to shared and non-shared environmental factors, underscoring the complexity of quantifying the exposome's influence on health outcomes. Secondly, we introduce the importance of advanced data-driven methods in large cohort studies for exposomic measurements. Here, we introduce the exposome-wide association study (ExWAS), an approach designed for systematic discovery of relationships between phenotypes and various exposures, identifying significant associations while controlling for multiple comparisons. We advocate for the standardized use of the term “exposome-wide association study, ExWAS,” to facilitate clear communication and literature retrieval in this field. The paper aims to guide future health researchers in understanding and evaluating exposomic studies. Our discussion extends to emerging topics, such as FAIR Data Principles, biobanked healthcare datasets, and the functional exposome, outlining the future directions in exposomic research. This abstract provides a succinct overview of our comprehensive approach to understanding the complex dynamics of the exposome and its significant implications for human health.
本文探讨了暴露体概念及其在阐明环境暴露与人类健康之间相互作用方面的作用。我们介绍了对暴露体研究至关重要的两个关键概念。首先,我们讨论了遗传和环境对表型的共同影响,强调了可归因于共有和非共有环境因素的变异,突出了量化暴露体对健康结果影响的复杂性。其次,我们介绍了在大型队列研究中采用先进的数据驱动方法进行暴露组测量的重要性。在这里,我们介绍了全暴露组关联研究(ExWAS),这种方法旨在系统地发现表型与各种暴露之间的关系,在控制多重比较的同时确定显著的关联。我们提倡标准化使用 "全暴露体关联研究,ExWAS "这一术语,以促进该领域的清晰交流和文献检索。本文旨在指导未来的健康研究人员理解和评估暴露组学研究。我们的讨论延伸到了新出现的话题,如 FAIR 数据原则、生物库医疗数据集和功能性暴露组,勾勒出了暴露组研究的未来方向。本摘要简明扼要地概述了我们理解暴露组复杂动态及其对人类健康重大影响的综合方法。
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引用次数: 0
The exposome at NIEHS: from workshops to manuscripts. NIEHS的暴露:从工作坊到手稿。
Pub Date : 2023-11-30 eCollection Date: 2023-01-01 DOI: 10.1093/exposome/osad011
Gary W Miller
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引用次数: 0
The Exposome and Nutritional Pharmacology and Toxicology: A New Application for Metabolomics 暴露体与营养药理学和毒理学:代谢组学的新应用
Pub Date : 2023-11-23 DOI: 10.1093/exposome/osad008
Blake R Rushing, A. Thessen, Ghada A Soliman, A. Ramesh, Susan J. Sumner
The exposome refers to all of the internal and external life-long exposures that an individual experiences. These exposures, either acute or chronic, are associated with changes in metabolism that will positively or negatively influence the health and well-being of individuals. Nutrients and other dietary compounds modulate similar biochemical processes and have the potential in some cases to counteract the negative effects of exposures or enhance their beneficial effects. We present herein the concept of Nutritional Pharmacology/Toxicology which uses high-information metabolomics workflows to identify metabolic targets associated with exposures. Using this information, nutritional interventions can be designed toward those targets to mitigate adverse effects or enhance positive effects. We also discuss the potential for this approach in precision nutrition where nutrients/diet can be used to target gene-environment interactions and other subpopulation characteristics. Deriving these “nutrient cocktails” presents an opportunity to modify the effects of exposures for more beneficial outcomes in public health.
暴露体指的是一个人终生经历的所有内部和外部暴露。这些暴露,无论是急性还是慢性,都与新陈代谢的变化有关,会对个人的健康和福祉产生积极或消极的影响。营养素和其他膳食化合物会调节类似的生化过程,在某些情况下有可能抵消暴露的负面影响或增强其有益作用。我们在此提出营养药理学/毒理学的概念,它利用高信息代谢组学工作流程来确定与暴露相关的代谢目标。利用这些信息,可以针对这些靶点设计营养干预措施,以减轻不良影响或增强积极作用。我们还讨论了这种方法在精准营养学中的应用潜力,在精准营养学中,营养素/饮食可用于针对基因-环境相互作用和其他亚人群特征。这些 "鸡尾酒营养素 "的产生为改变暴露效应以获得更有益的公共健康结果提供了机会。
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引用次数: 0
Community-level exposomics: A population-centered approach to address public health concerns 社区层面的暴露研究:以人口为中心解决公共卫生问题的方法
Pub Date : 2023-11-16 DOI: 10.1093/exposome/osad009
Jeanette A Stingone, Andrew M Geller, D. Hood, Konstantinos C Makris, Charles P Mouton, J. C. States, Susan J. Sumner, K. L. Wu, Arcot K Rajasekar
Environmental factors affecting health and vulnerability far outweigh genetics in accounting for disparities in health status and longevity in US communities. The concept of the exposome, the totality of exposure from conception onwards, provides a paradigm for researchers to investigate the complex role of the environment on the health of individuals. We propose a complementary framework, community-level exposomics, for population-level exposome assessment. The goal is to bring the exposome paradigm to research and practice on the health of populations, defined by various axes including geographic, social, and occupational. This framework includes the integration of community-level measures of the built, natural and social environments, environmental pollution-derived from conventional and community science approaches, internal markers of exposure that can be measured at the population-level and early responses associated with health status that can be tracked using population-based monitoring. Primary challenges to the implementation of the proposed framework include needed advancements in population-level measurement, lack of existing models with the capability to produce interpretable and actionable evidence and the ethical considerations of labeling geographically-bound populations by exposomic profiles. To address these challenges, we propose a set of recommendations that begin with greater engagement with and empowerment of affected communities and targeted investment in community-based solutions. Applications to urban settings and disaster epidemiology are discussed as examples for implementation.
在造成美国社区健康状况和寿命差异方面,影响健康和脆弱性的环境因素远远超过了遗传因素。暴露组的概念,即从受孕开始的全部暴露,为研究人员提供了一个范例,用以研究环境对个人健康的复杂作用。我们提出了一个补充框架,即社区级暴露组学(community-level exposomics),用于人口级暴露组评估。我们的目标是将暴露组范式应用于以地理、社会和职业等不同轴心定义的人群健康研究和实践。这一框架包括整合社区层面的建筑、自然和社会环境措施、从传统和社区科学方法中得出的环境污染、可在人群层面测量的暴露内部标记以及可通过人群监测跟踪的与健康状况相关的早期反应。实施拟议框架所面临的主要挑战包括:需要在人群水平测量方面取得进展;缺乏有能力提供可解释和可操作证据的现有模型;以及通过暴露组学特征对受地理限制的人群进行标记的伦理考虑。为了应对这些挑战,我们提出了一系列建议,首先是加强受影响社区的参与和赋权,并有针对性地投资于以社区为基础的解决方案。我们还讨论了在城市环境和灾害流行病学中的应用,作为实施的范例。
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引用次数: 0
A roadmap to advance exposomics through federation of data 通过数据联合推进暴露组学的路线图
Pub Date : 2023-11-14 DOI: 10.1093/exposome/osad010
Charles P Schmitt, Jeanette A Stingone, Arcot Rajasekar, Yuxia Cui, Xiuxia Du, Chris Duncan, Michelle Heacock, Hui Hu, Juan R Gonzalez, Paul D Juarez, Alex I Smirnov
Abstract The scale of the human exposome, which covers all environmental exposures encountered from conception to death, presents major challenges in managing, sharing, and integrating a myriad of relevant data types and available data sets for the benefit of exposomics research and public health. By addressing these challenges, the exposomics research community will be able to greatly expand on its ability to aggregate study data for new discoveries, construct and update novel exposomics data sets for building artificial intelligence and machine learning-based models, rapidly survey emerging issues, and advance the application of data-driven science. The diversity of the field, which spans multiple subfields of science disciplines and different environmental contexts, necessitates adopting data federation approaches to bridge between numerous geographically and administratively separated data resources that have varying usage, privacy, access, analysis, and discoverability capabilities and constraints. This paper presents use cases, challenges, opportunities, and recommendations for the exposomics community to establish and mature a federated exposomics data ecosystem.
人类暴露体的规模涵盖了从怀孕到死亡所遇到的所有环境暴露,在管理、共享和整合无数相关数据类型和可用数据集以造福暴露体研究和公共卫生方面提出了重大挑战。通过解决这些挑战,暴露组学研究界将能够极大地扩展其收集新发现研究数据的能力,构建和更新新的暴露组学数据集,用于构建基于人工智能和机器学习的模型,快速调查新出现的问题,并推进数据驱动科学的应用。该领域的多样性跨越了科学学科的多个子领域和不同的环境背景,因此需要采用数据联合方法在众多地理上和管理上分离的数据资源之间架起桥梁,这些数据资源具有不同的使用、隐私、访问、分析和可发现性能力和约束。本文提出了用例、挑战、机遇和建议,供暴露学社区建立和成熟联合暴露学数据生态系统。
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引用次数: 0
Historical Exposomics: A Manifesto 历史揭秘学:一份宣言
Pub Date : 2023-08-18 DOI: 10.1093/exposome/osad007
Dagny Aurich, Aida Horaniet Ibañez, C. Hissler, Simon Kreipl, L. Pfister, Emma L. Schymanski, A. Fickers
The exposome complements information captured in the genome by covering all external influences and internal (biological) responses of a human being from conception onwards. Such a paradigm goes beyond a single scientific discipline and instead requires a truly interdisciplinary approach. The concept of “historical exposomics” could help bridge the gap between “nature” and “nurture” using both natural and social archives to capture the influence of humans on earth (the Anthropocene) in an interdisciplinary manner. The LuxTIME project served as a test bed for an interdisciplinary exploration of the historical exposome, focusing on the Belval area located in the Minett region in southern Luxembourg. This area evolved from a source of mineral water to steel production through to the current campus for research and development. This article explores the various possibilities of natural and social archives that were considered in creating the historical exposome of Belval and reflects upon possibilities and limitations of the current approaches in assessing the exposome using purely a natural science approach. Issues surrounding significance, visualization, and availability of material suitable to form natural archives are discussed in a critical manner. The “Minett Stories” are presented as a way of creating new historical narratives to support exposome research. New research perspectives on the history of the Anthropocene were opened by investigating the causal relationships between factual evidence and narrative evidence stemming from historical sources. The concept of historical exposome presented here may thus offer a useful conceptual framework for studying the Anthropocene in a truly interdisciplinary fashion.
通过覆盖人类从受孕开始的所有外部影响和内部(生物)反应,暴露体补充了基因组中捕获的信息。这种范式超越了单一的科学学科,而是需要真正的跨学科方法。"历史暴露学"的概念可以帮助弥合"自然"和"教养"之间的差距,利用自然和社会档案以跨学科的方式捕捉人类对地球的影响(人类世)。LuxTIME项目作为一个跨学科探索历史暴露的试验台,重点放在位于卢森堡南部Minett地区的Belval地区。这个地区从矿泉水的来源发展到钢铁生产,再到现在的研究和开发园区。本文探讨了自然和社会档案的各种可能性,这些可能性在创建贝尔瓦尔的历史曝光中被考虑,并反映了目前使用纯自然科学方法评估曝光的可能性和局限性。围绕的意义,可视化和材料的可用性,适合形成自然档案的关键方式进行了讨论。“米奈特故事”是一种创造新的历史叙事的方式,以支持揭露性研究。通过调查事实证据和历史证据之间的因果关系,开辟了人类世历史研究的新视角。因此,这里提出的历史暴露概念可能为以真正跨学科的方式研究人类世提供一个有用的概念框架。
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引用次数: 0
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