TOXsIgN organization overview

The TOXsIgN repository is organized in a four-layer architecture (Project > Assay > Factor > Signature) associated with a unique identifier. The project layer covers one or several studies addressing specific questions. Each study in turn is associated with at least one assay that assesses the exposure of a given study model (e.g., cell culture, living animal, human population) to at least one chemical (e.g., pesticide, plasticizer, drug, or endocrine disruptor), physical (e.g., type of radiation or temperature) or biological (e.g., pathogen or parasite) agent at a given dose and for a given time of exposure. This organization makes TOXsIgN compatible with mixtures and transgenerational studies. A toxicogenomic signature is defined as the description of the “omic” (e.g. epigenomic, transcriptomic, or proteomic) effects on individuals or their descendants of exposure to single or combined environmental agents.

Register

In order to register you will need to click on the “Register” button on the top right-hand corner of the website.

You will then need to enter your first and last name, your institute name, a valid e-mail address, your professional address and password. Before you can login, you must active your account with the link sent to your email address. If you don't get an email: Check your Spam or Bulk Mail folders.

Update my project

In order to update the information associated to a given project, including associated studies, assays, factors and signatures, please navigate to the project view and then re-upload the updated TOXsIgN spreadsheet describing the corresponding project using the “Update” button.

Uploading signatures or additional files

In order to upload a file to a given signature, please navigate to the signature view (http://toxsign.genouest.org/app/#/browse?dataset=TSSXXXX) and click on the “Upload” button associated with the signature.

Four types of files can be uploaded:

• UP: containing the set of up-regulated/overexpressed/positively altered genes.
• DOWN: containing the set of down-regulated/underexpressed/negatively altered genes.
• INTERROGATED: containing the entire set of interrogated genes.
• Additional file: Any type of file related to the signature.
Please make sure that the uploaded files should have the same name as the one indicated in the Excel spreadsheet. Importantly, the uploaded files (UP, DOWN and INTERROGATED) must be text file with only one identifier (Entrez gene) per line.

Project status

By default, each submitted project and its related signatures are tagged with a “private” status meaning that only authorized users (the owner but also coauthors) can access the uploaded data. At this stage, information can still be modified simply by uploading an updated version of the Excel template. A button is available on the web interface for each project to request the TOXsIgN administrators to change the project status from private to public. If “warnings” are still detected, this demand is rejected. The administrators will then help the investigators make the necessary modifications to change the status. Full instructions and examples of the submission procedure are provided in the tutorial section.

How to fill the TOXsIgN spreadsheet

During the submission procedure, investigators should record all required information in a dedicated Excel template. This document is divided into six sheets dedicated to: i) the description of one project; ii) of at least one study; iii) of at least one assay; iv) of at least one experimental factor; v) of at least one signature; finally, vi) the last sheet describes all ontologies used in TOXsIgN. This template is frequently updated. You should always make sure that you are using the latest version.

Project

The project layer (associated with an identifier with the “TSP” prefix) covers one or several studies and is described with the following information:

• A unique project ID (“TSP” prefix): Please do not modify it.
• A title (XXX words/letters): Please provide a unique title describing the overall project.
• A description (XXX words/letters): Please provide a brief description of this project. The abstract from the associated publication may be suitable. Multiple summary lines can be included.
• PubMed link(s) (comma-separated): [Optional]: Please specify a valid PubMed identifier (PMID) corresponding to the submitted project. This information is usually not available at the time of submission - it can be added later after manuscript acceptance.
• Crosslink(s): [Optional] Please specify web links to other we resources that will supplement all these information. Make sure these wen links are stable.

Studies

One study addresses specific questions and is associated with at least one assay. There are two types of study: interventional and observational studies. An interventional study is defined as: A study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions. An observational study is defined as: A biomedical or behavioral research study of human subjects designed to assess risk factors for disease development or progression, assess natural history of risk factors or disease, identify variations based on geographic or personal characteristics (such as race/ethnicity or gender), track temporal trends, or describe patterns of clinical care and treatment in absence of specific study-mandated interventions. Each line in the corresponding sheet describes one study that is described using the following information:

• A unique study ID (TSS prefix): Please do not modify it.
• Associated project: Please indicate the project ID (TSP) associated to this study.
• A title (XXX words/letters): Please provide a unique title describing the overall study.
• A description (XXX words/letters): Please provide a brief description of the study. The abstract from the associated publication may be suitable. Multiple summary lines can be included.
• Design: [Optional] Please provide a description of the experimental design
• Result(s): [Optional] Please provide a short description of the observed outcome(s) of this study.
• Study type: Please choose between “interventional” or “observational”.
• Inclusion period: [Optional & only for observational study] Please indicate the time window during which subjects were included in the study: specify starting and ending dates.
• Inclusion criteria: [Optional & only for observational study] Please indicate the attribute of subjects that are essential for their selection to participate.
• Exclusion criteria: [Optional & only for observational study] Please indicate the attribute or response that is incompatible with the conduction of the study, leading to the exclusion of subjects from the study.
• Follow up: [Optional & only for observational study] Please indicate the duration between the inclusion and the outcome (prospective study), or between the exposure and the outcome (retrospective study): specify duration or starting and ending date.
• Population size: [Optional & only for observational study] Please give the number of subjects participating in the study, after consideration of inclusion and exclusion criteria.
• Pubmed Id(s) (comma-separated): [Optional] [Optional]: Please specify a valid PubMed identifier (PMID) corresponding to the submitted project. This information is usually not available at the time of submission - it can be added later after manuscript acceptance.

Assays

The assay assesses the exposure of a given model (e.g., cell culture, living animal, organ explant, human population) to at least one factor at a given dose and for a given time of exposure.
An assay is in general an experiment that converts either a material or data sample, into a new material or data sample, via a protocol. Multiple assays can be connected to a study. Each line describes an assay and each assay is described using the following information:

• A unique Assay ID (“TST” prefix): Please do not modify it.
• Associated study: Please indicate the Study identifier (TSS) associated to this assay.
• A title: Please provide a unique title describing the assay
• Organism: [Optional & use ontologies] Please indicate the organism from which the biological material was derived (pleas use the controlled vocabularies).
• Sex: [Optional] Please indicate the gender.
• Developmental stage: [Optional] Please indicate the developmental stage.
• Tissue: [Optional & use ontologies] Please indicate the tissue from which the biological material was derived.
• Generation: [Optional] Please indicate the generation.
• Cell: [Optional & use ontologies] Please indicate the cell-type from which the biological material was derived.
• Cell line: [Optional & use ontologies] Please indicate the cell-line used.
• Experimental type: [Optional] Please indicate the experimental type (in vivo, ex vivo, in vitro...).
• Population age: [Optional & only for observational study].
• Geographical location: [Optional & only for observational study].
• Control / Reference: [Optional & only for observational study].
• Biological matrice: [Optional & only for observational study].
• Additional information: [Optional] Please mention any other information not provided in the other fields.

Factors

An experimental factor describes at least one chemical (e.g. pesticides, plasticizers, drugs, endocrine disruptors), physical (e.g. radiations, temperature) or biological (e.g. pathogens, parasites) factor at a given dose and at a given time of exposure. This organization makes TOXsIgN compatible with mixture studies. Factors are currently restricted to chemical compounds. Each line describes one factor and each factor is described using the following information:

• A unique Factor ID: Please do not modify it.
• Associated assay: Please indicate the Assay identifier (TST prefix) associated with this experimental factor.
• Exposition factor: Please indicate the type of factor (biological, physical or chemical). Currently TOXsIgN is restricted to chemical factor.
• Chemical name: [Optional & use ontologies] Please indicate the name of the chemical factor.
• Biological: [Not available] Please indicate the name of the biological factor.
• Physical name: [Not available] Please indicate the name of the physical factor.
• Vehicle: Please indicate the vehicle used.
• Route: Please indicate the route used.
• Dose: Please indicate the administered dose.
• Exposure duration: Please indicate the exposition time.
• Exposure frequency: [Optional] Please describe the chronical exposition protocol.
• Additional information: [Optional] Please mention any other information not provided in the other fields.

Signatures

A toxicological signature is defined as the description of physiological, cellular, molecular or omic effects on individuals or their descendants, after exposure to single or combined environmental factors. You can create either physiological, molecular or genomic signatures.
Physiological signature: physiological responses (i.e. disease, pathway or biological process alteration) after an exposure to single or combined environmental factors.
Molecular signature: molecular responses after an exposure to single or combined environmental factors.
Genomic signature: set of genes whose expression is known to be positively or negatively altered after an exposure to single or combined environmental factors. Each line describes one signature and each factor is described using the following information:

• A unique Signature ID (TSS prefix): Please do not modify it.
• Associated study: Please indicate the Study identifier (TSS) associated with this signature.
• Associated assay: Please indicate the Assay identifier (TST) associated with this signature.
• Title: Please provide a unique title describing the overall signature.
• Type: Please indicate the signature type (physiological, molecular or genomic).
• Organism: [Optional & use ontologies] Please indicate the organism from which the biological material was derived.
• Sex: [Optional] Please indicate the gender.
• Developmental stage: [Optional] Please indicate the developmental stage.
• Tissue: [Optional & use ontologies] Please indicate the tissue from which the biological material was derived.
• Cell: [Optional & use ontologies] Please indicate the cell-type from which the biological material was derived.
• Cell line: [Optional & use ontologies] Please indicate the cellline used.
• Generation: [Optional] Please indicate the generation (F0 is default).
• Associated phenotype, diseases processes or pathway / outcome: [Optional & use ontologies & only for physiological and molecular signatures] Please indicate the observed outcome(s) after exposure using controlled vocabularies.
• Technology used: [Optional & only for genomic signature] Please indicate the technology used to obtain the signature.
• Platform: [Optional & only for genomics signatures] Please indicate the GEO Platform accession number (GPLxxx).
• Control / unexposed (n=): [Optional & only for obs. studies] Please indicate the number of subjects in the reference group for the statistical comparison.
• Case / exposed (n=): [Optional & only for obs. studies] Please indicate the number of subjects in the group to be compared to the reference, for the present statistical comparison.
• Observed effect: [Optional & only for physiological and molecular signatures] Please describe the observed trend of the associated phenotype (increase, decrease, NA, ...).
• Statistical significance: [Optional & use ontologies & only for obs. studies] Please indicate whether the associations reach the statistical significance or not, considering a standard threshold of p-value <\0.05 (or less, in case of correction for multiple testing).
• Statistical value: [Optional & use ontologies & only for obs. studies] Please provide main statistical information (odd ratio / relative risk and confidence interval, p-value, beta, rho, p-trend …).
• Statistical adjustments: [Optional & use ontologies & only for obs. studies] Please provide the list of the main covariates on which statistical adjustment have been performed (e.g. using multivariate analyses), or variables neutralized by matching, stratification or standardization.
• Other statistical information: [Optional & use ontologies & only for obs. studies] Please mention any other statistical information (odd ratio / relative risk and confidence interval, p-value, beta, rho, p-trend …).
• Identifier type: [Optional & only for genomics signatures] Please indicate the type of identifier used for the signature. Default is Entrez gene in TOXsIgN.
• UP: [Optional & only for genomics signatures] Please upload the file containing the set of up-regulated/overexpressed/positively altered genes.
• DOWN: [Optional & only for genomics signatures] Please upload the file containing the set of down-regulated/underexpressed/negatively altered genes.


• INTERROGATED: [Only for genomics signatures] Please upload the file containing the entire set of interrogated genes.
• Additional file: [Optional] Please upload any additional files.
• Number of sample: [Optional] Please indicate the number of exposed samples.
• Fold change: [Optional] Please indicate the fold change cutoff used for the statistical filtration.
• Pvalue: [Optional] Please indicate the Pvalue threshold used for the statistical filtration.
• Statistical processing: [Optional] Please mention any other relevant information not provided in the other fields.