Exposome-Explorer: a manually-curated database on biomarkers of exposure to dietary and environmental factors

Published online 24 October 2016 Nucleic Acids Research, 2017, Vol. 45, Database issue D979–D984 doi: 10.1093/nar/gkw980 Exposome-Explorer: a manually-curated database on biomarkers of exposure to dietary and environmental factors Vanessa Neveu1 , Alice Moussy1 , Héloı̈se Rouaix1 , Roland Wedekind1 , Allison Pon2 , Craig Knox2 , David S. Wishart2 and Augustin Scalbert1,* 1 International Agency for Research on Cancer (IARC), Nutrition and Metabolism Section, Biomarkers Group, 150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France and 2 Department of Computing Science, University of Alberta, Edmonton, AB T6G 2E8, Canada Received August 10, 2016; Revised October 07, 2016; Editorial Decision October 11, 2016; Accepted October 12, 2016 ABSTRACT Exposome-Explorer (http://exposome-explorer.iarc. fr) is the first database dedicated to biomarkers of exposure to environmental risk factors. It contains detailed information on the nature of biomarkers, their concentrations in various human biospecimens, the study population where measured and the analytical techniques used for measurement. It also contains correlations with external exposure measurements and data on biological reproducibility over time. The data in Exposome-Explorer was manually collected from peer-reviewed publications and organized to make it easily accessible through a web interface for in-depth analyses. The database and the web interface were developed using the Ruby on Rails framework. A total of 480 publications were analyzed and 10 510 concentration values in blood, urine and other biospecimens for 692 dietary and pollutant biomarkers were collected. Over 8000 correlation values between dietary biomarker levels and food intake as well as 536 values of biological reproducibility over time were also compiled. ExposomeExplorer makes it easy to compare the performance between biomarkers and their fields of application. It should be particularly useful for epidemiologists and clinicians wishing to select panels of biomarkers that can be used in biomonitoring studies or in exposome-wide association studies, thereby allowing them to better understand the etiology of chronic diseases. INTRODUCTION Environmental factors play a major role in the etiology of cancers, cardiovascular disease, and other chronic diseases. These factors are diverse in nature and include diet, drugs, cosmetics, household chemicals, pollutants, or infectious agents. Exposures to these factors vary widely between populations, and between individuals within the same population. Therefore, their measurement is essential to: (i) study associations in epidemiological studies with disease outcomes and assess their contribution to disease risk, (ii) monitor exposures to disease risk factors in population studies and (iii) assess subject compliance in clinical trials or large intervention studies (1–3). Exposure measurements have traditionally relied on the use of questionnaires and self-reporting. However, these methods are known to be error-prone and biased. Molecular biomarkers, on the other hand, are more direct and objective indicators of exposure. Indeed, biomarkers of exposure have been increasingly used since the early 1980s, thanks to rapid progress in analytical techniques and the establishment of large cohorts with extensive biospecimen collections. Biomarkers of exposure can be compounds present in the environment and absorbed in the gut after ingestion, inhaled in lungs, or absorbed through the skin. They can also be metabolic end-products derived from environmental compounds that were metabolized by the liver and other tissues, and the microbiota. They may also be macromolecular indicators of environmental effects (e.g. enzymes, proteins or RNA transcripts related to the status of a nutrient or toxic agent). Over the past 30 years several hundred biomarkers of exposure have been measured and reported in blood, urine and other biospecimens in various populations. However, this information is scattered over hundreds of publications under many diverse titles and subject headings. This makes the identification of these biomarkers along with their comparative performance, their field of application and their concentration ranges in different populations difficult. Historically, most biomarkers of exposure have been measured individually using compound-specific assays. However, with * To whom correspondence should be addressed. Tel: +33 4 72 73 80 95; Email:  C The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact D980 Nucleic Acids Research, 2017, Vol. 45, Database issue the emergence of various omics technologies there is an increasing tendency to characterize exposures more comprehensively. Indeed, modern mass spectrometry techniques now allow the measurement of thousands of compounds in blood, urine or other biospecimens in a single analytical run. These developments are leading, increasingly, to the reporting of data from multiple markers of exposure. Modern omics technologies should also allow the translation into practice of the concept of the exposome (the totality of exposures of a particular individual over lifetime (4,5)) and the development of exposome-wide association studies (EWAS) (2,6–8). These newly emerging trends in exposure science, combined with the growing volume of comprehensive exposure data being published, make the establishment of a centralized, online database on biomarkers of exposure particularly critical. To date, relatively little effort has been directed to collecting and organizing data on biomarkers of exposure. The ExpoCastDB database contains information on exposure to environmental chemicals such as PAHs, PCBs, nonylphenols, or pesticides (http://actor.epa.gov/actor/faces/ExpoCastDB/Home.jsp). ExpoCastDB contains information on compound concentrations in various environmental matrices but very limited data in biospecimens. The Comparative Toxicogenomics Database (CTD) is the only online database containing a large number of concentration values in blood, urine and other biospecimens extracted from the scientific literature (9). The CTD contains about 35 000 concentration values in various biospecimens for ∼250 organic and inorganic compounds. While ExpoCastDB and CTD are very useful and important databases, they contain only limited information on biomarkers of exposure. Here we describe Exposome-Explorer, the first database dedicated to exposure biomarkers. Exposome-Explorer consolidates the diffuse exposure biomarker data scattered throughout the literature. It contains comprehensive information on almost 500 biomarkers of exposur (...truncated)