DRomics: A Turnkey Tool to Support the Use of the Dose–Response Framework for Omics Data in Ecological Risk Assessment

International audienceOmics approaches (e.g. transcriptomics, metabolomics) are promising for ecological risk assessment (ERA) since they provide mechanistic information and early warning signals. A crucial step in the analysis of omics data is the modelling of concentration-dependency which may have different trends including monotonic (e.g. linear, exponential) or biphasic (e.g. U shape, bell shape) forms. The diversity of responses raises challenges concerning detection and modelling of significant responses and effect concentration (EC) derivation. Furthermore, handling high-throughput datasets is time-consuming and requires effective and automated processing routines. Thus, we developed an open source tool (DRomics,available as an R-package and as a web-based service) which, after elimination of molecular responses (e.g. gene expressions from microarrays) with no concentration-dependency and/or high variability, identifies the best model for concentration-response curve description. Subsequently, an EC (e.g. a benchmark dose) is estimated from each curve and curves are classified based on their model parameters. This tool is especially dedicated to manage data obtained from an experimental design favoring a greatnumber of tested doses rather than a great number of replicates and also to handle properly monotonic and biphasic trends. The tool finally restitutes a table of results that can be directly used to perform ERA approaches

Conference Report: Deuxièmes Rencontres R

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DRomics, a workflow to exploit dose-response omics data in ecotoxicology

Omics technologies has opened new possibilities to assess environmental risks and to understand the mode(s) of action of pollutants. Coupled to dose-response experimental designs, they allow a non-targeted assessment of organism responses at the molecular level along an exposure gradient. However, describing the dose-response relationships on such high-throughput data is no easy task. In a first part, we review the software available for this purpose, and their main features. We set out arguments on some statistical and modeling choices we have made while developing the R package DRomics and its positioning compared to others tools. The DRomics main analysis workflow is made available through a web interface, namely a shiny app named DRomics-shiny. Next, we present the new functionalities recently implemented. DRomics has been augmented especially to be able to handle varied omics data considering the nature of the measured signal (e.g. counts of reads in RNAseq) and the way data were collected (e.g. batch effect, situation with no experimental replicates). Another important upgrade is the development of tools to ease the biological interpretation of results. Various functions are proposed to visualize, summarize and compare the responses, for different biological groups (defined from biological annotation), optionally at different experimental levels (e.g. measurements at several omics level or in different experimental conditions). A new shiny app named DRomicsInterpreter-shiny is dedicated to the biological interpretation of results. The institutional web page https://lbbe.univ-lyon1.fr/fr/dromics gathers links to all resources related to DRomics, including the two shiny applications

Unknown age in health disorders: A method to account for its cumulative effect and an application to feline viruses interactions.

Remerciements ECOFECTInternational audienceParasite interactions have been widely evidenced experimentally but field studies remain rare. Such studies are essential to detect interactions of interest and access (co)infection probabilities but face methodological obstacles. Confounding factors can create statistical associations, i.e. false parasite interactions. Among them, host age is a crucial covariate. It influences host exposition and susceptibility to many infections, and has a mechanical effect, older individuals being more at risk because of a longer exposure time. However, age is difficult to estimate in natural populations. Hence, one should be able to deal at least with its cumulative effect. Using a SI type dynamic model, we showed that the cumulative effect of age can generate false interactions theoretically (deterministic modeling) and with a real dataset of feline viruses (stochastic modeling). The risk to wrongly conclude to an association was maximal when parasites induced long-lasting antibodies and had similar forces of infection. We then proposed a method to correct for this effect (and for other potentially confounding shared risk factors) and made it available in a new R package, Interatrix. We also applied the correction to the feline viruses. It offers a way to account for an often neglected confounding factor and should help identifying parasite interactions in the field, a necessary step towards a better understanding of their mechanisms and consequences

Sex‐specific actuarial and reproductive senescence in zoo‐housed tiger ( Panthera tigris ): The importance of sub‐species for conservation

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adegraphics: An S4 Lattice-Based Package for the Representation of Multivariate Data

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rbioacc: An R-package to analyze toxicokinetic data

International audienceThe R-package rbioacc allows to analyse experimental data from bioaccumulation tests where organisms are exposed to a chemical (exposure) then put into clean media (depuration). Internal concentrations are measured over time during the experiment. rbioacc provides turnkey functions to visualise and analyse such data. Under a Bayesian framework, rbioacc fits a generic one-compartment toxicokinetic model built from the data. It provides TK parameter estimates (uptake and elimination rates) and standard bioaccumulation metrics. All parameter estimates, bioaccumulation metrics and predictions of internal concentrations are delivered with their uncertainty. Bioaccumulation metrics are provided in support of environmental risk assessment, in full compliance with regulatory requirements required to approve market release of chemical substances. This paper provides worked examples of the use of rbioacc from data collected through standard bioaccumulation tests, publicly available within the scientific literature. These examples constitute step-by-step user-guides to analyse any new data set, uploaded in the right format

Multivariate analysis of ecological data with ade4

This book introduces the ade4 package for R which provides multivariate methods for the analysis of ecological data. It is implemented around the mathematical concept of the duality diagram, and provides a unified framework for multivariate analysis. The authors offer a detailed presentation of the theoretical framework of the duality diagram and also of its application to real-world ecological problems. These two goals may seem contradictory, as they concern two separate groups of scientists, namely statisticians and ecologists. However, statistical ecology has become a scientific discipline of its own, and the good use of multivariate data analysis methods by ecologists implies a fair knowledge of the mathematical properties of these methods. The organization of the book is based on ecological questions, but these questions correspond to particular classes of data analysis methods. The first chapters present both usual and multiway data analysis methods. Further chapters are dedicated for example to the analysis of spatial data, of phylogenetic structures, and of biodiversity patterns. One chapter deals with multivariate data analysis graphs. In each chapter, the basic mathematical definitions of the methods and the outputs of the R functions available in ade4 are detailed in two different boxes. The text of the book itself can be read independently from these boxes. Thus the book offers the opportunity to find information about the ecological situation from which a question raises alongside the mathematical properties of methods that can be applied to answer this question, as well as the details of software outputs. Each example and all the graphs in this book come with executable R code

Taking full advantage of modelling to better assess environmental risk due to xenobiotics

International audienceIn the European Union, more than 100,000 man-made chemical substances are awaiting an environmental risk assessment (ERA). Simultaneously, ERA of these chemicals has now entered a new era requiring determination of risks for physiologically diverse species exposed to several chemicals, often in mixtures. Additionally, recent recommendations from regulatory bodies underline a crucial need for the use of mechanistic effect models, allowing assessments that are not only ecologically relevant, but also more integrative, consistent and efficient. At the individual level, toxicokinetic-toxicodynamic (TKTD) models are particularly encouraged for the regulatory assessment of pesticide-related risks on aquatic organisms. In this paper, we first briefly present a classical dose-response model to showcase the on-line MOSAIC tool, which offers all necessary services in a turnkey web platform, whatever the type of data analyzed. Secondly, we focus on the necessity to account for the time-dimension of the exposure by illustrating how MOSAIC can support a robust calculation of bioaccumulation metrics. Finally, we show how MOSAIC can be of valuable help to fully complete the EFSA workflow regarding the use of TKTD models, especially with GUTS models, providing a user-friendly interface for calibrating, validating and predicting survival over time under any time-variable exposure scenario of interest. Our conclusion proposes a few lines of thought for an easier use of modelling in ERA