The ReproGenomics Viewer: an integrative cross-species toolbox for the reproductive science community.

International audienceWe report the development of the ReproGenomics Viewer (RGV), a multi-and cross-species working environment for the visualization, mining and comparison of published omics data sets for the reproductive science community. The system currently embeds 15 published data sets related to gametogenesis from nine model organisms. Data sets have been curated and conveniently organized into broad categories including biological topics, technologies, species and publications. RGV's modular design for both organisms and genomic tools enables users to upload and compare their data with that from the data sets embedded in the system in a cross-species manner. The RGV is freely available at http://rgv.genouest.org

The Male Fertility Gene Atlas: a web tool for collecting and integrating OMICS data in the context of male infertility

International audienceStudy question: How can one design and implement a system that provides a comprehensive overview of research results in the field of epi-/genetics of male infertility and germ cells?Summary answer: Working at the interface of literature search engines and raw data repositories, the newly developed Male Fertility Gene Atlas (MFGA) provides a system that can represent aggregated results from scientific publications in a standardized way and perform advanced searches, for example based on the conditions (phenotypes) and genes related to male infertility.What is known already: PubMed and Google Scholar are established search engines for research literature. Additionally, repositories like Gene Expression Omnibus and Sequence Read Archive provide access to raw data. Selected processed data can be accessed by visualization tools like the ReproGenomics Viewer.Study design, size, duration: The MFGA was developed in a time frame of 18 months under a rapid prototyping approach.Participants/materials, setting, methods: In the context of the Clinical Research Unit 'Male Germ Cells' (CRU326), a group of around 50 domain experts in the fields of male infertility and germ cells helped to develop the requirements engineering and feedback loops. They provided a set of 39 representative and heterogeneous publications to establish a basis for the system requirements.Main results and the role of chance: The MFGA is freely available online at https://mfga.uni-muenster.de. To date, it contains 115 data sets corresponding to 54 manually curated publications and provides an advanced search function based on study conditions, meta-information and genes, whereby it returns the publications' exact tables and figures that fit the search request as well as a list of the most frequently investigated genes in the result set. Currently, study data for 31 different tissue types, 32 different cell types and 20 conditions are available. Also, ∼8000 and ∼1000 distinct genes have been found to be mentioned in at least 10 and 15 of the publications, respectively.Large scale data: Not applicable because no novel data were produced.Limitations, reasons for caution: For the most part, the content of the system currently includes the selected publications from the development process. However, a structured process for the prospective literature search and inclusion into the MFGA has been defined and is currently implemented.Wider implications of the findings: The technical implementation of the MFGA allows for accommodating a wide range of heterogeneous data from aggregated research results. This implementation can be transferred to other diseases to establish comparable systems and generally support research in the medical field.Study funding/competing interest(s): This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit 'Male Germ Cells: from Genes to Function' (CRU326). The authors declare no conflicts of interest

PepPSy: a web server to prioritize gene products in experimental and biocuration workflows

Among the 20 000 human gene products predicted from genome annotation, about 3000 still lack validation at protein level. We developed PepPSy, a user-friendly gene expression-based prioritization system, to help investigators to determine in which human tissues they should look for an unseen protein. PepPSy can also be used by biocurators to revisit the annotation of specific categories of proteins based on the 'omics' data housed by the system. In this study, it was used to prioritize 21 dubious protein-coding genes among the 616 annotated in neXtProt for reannotation. PepPSy is freely available at http://peppsy.genouest.or

PFOS disrupts key developmental pathways during hiPSC-derived cardiomyocyte differentiation in vitro

International audienceExposure to perfluorooctanesulfonic acid (PFOS) has been associated with congenital heart disease (CHD) and decreased birth weight. PFOS exposure can disrupt signaling pathways relevant for cardiac development in stem cell-derived cardiomyocyte assays, such as the PluriBeat assay, where spheroids of human induced pluripotent stem cells (hiPSCs) differentiate into contracting cardiomyocytes. Notably, cell line origin can also affect how the assay responds to chemical exposure. Herein, we examined the effect of PFOS on cardiomyocyte differentiation by transcriptomics profiling of two different hiPSC lines to see if they exhibit a common pattern of disruption. Two stages of differentiation were investigated: the cardiac progenitor stage and the cardiomyocyte stage. Many differentially expressed genes (DEGs) were observed between cell lines independent of exposure. However, 135 DEGs were identified as common between the two cell lines. Of these, 10 DEGs were associated with GO-terms related to the heart. PFOS exposure disrupted multiple signaling pathways relevant to cardiac development, including WNT, TGF, HH, and EGF. Of these pathways, genes related to the non-canonical WNTCa(2+) signaling was particularly affected. PFOS thus has the capacity to disrupt pathways important for cardiac development and function

A curated Domain centric shared Docker registry linked to the Galaxy toolshed

International audienceNowadays, Docker containers are used to ease application deployment, from command lines tools to cluster management1. This technology has a strong impact in bioinformatics where specialized software can often require multiple dependencies. It is a long term preservation solution for legacy and unmaintained tools and it enables a better process isolation in a multi-user environment. Docker as a way to quickly integrate new tools is already used with Galaxy. We have setup a functional prototype of a web registry of Docker images, BioShaDock,2 dedicated to bioinformatics tools and utilities. We created a set of tools descriptors based on Docker images available in our toolshed3. Even if a general purpose registry can be used to hold shared Docker containers, we think that a domain centric registry, e.g. for the French life science community through a registry linked to the cloud of the French Institute of Bioinformatics (IFB8), would have a significant impact on bioinformatician productivity and help to spread best practices. With a clear open source and domain orientation, it could federate container providers4,5 more easily. It would also be able to include validation and curation to eliminate redundant tools, organize versioning and standardize documentation. Future works will concern advanced searching capabilities, possible referencing within the ELIXIR Tools and Data Services Registry6 and in the IFB one (as the ELIXIR French node). We want also to contribute to standardize containers7 and evaluate if benchmarks5 could be produced from a meta-data enriched, Docker registry.References:1 Google Kubernetes, Docker container cluster management : kubernetes.io2 BioShaDock, a Bioinformatics Shared Docker registry : http://docker-ui.genouest.org3 GUGGO Galaxy Tooshed : http://toolshed.genouest.org4 Hexabio Docker repository : http://biodocker.github.io5 Nucleotid.es, continuous, objective and reproducible evaluation of genome assemblers using docker containers : http://nucleotid.es6 ELIXIR Tools and Data Services Registry : https://elixir-registry.cbs.dtu.dk7 Bioboxes, a standard for creating interchangable bioinformatics software containers : http://bioboxes.org8 IFB academic Cloud : http://www.france-bioinformatique.fr/?q=en/core/e-infrastructure-team/ifb-clou

The ReproGenomics Viewer: a multi-omics and cross-species resource compatible with single-cell studies for the reproductive science community

Motivation: Recent advances in transcriptomics have enabled unprecedented insight into gene expression analysis at a single-cell resolution. While it is anticipated that the number of publications based on such technologies will increase in the next decade, there is currently no public resource to centralize and enable scientists to explore single-cell datasets published in the field of reproductive biology. Results: Here, we present a major update of the ReproGenomics Viewer (RGV), a cross-species and cross-technology web-based resource of manually-curated sequencing datasets related to reproduction. The redesign of RGV's architecture is accompanied by significant growth of the database content including several landmark single-cell RNA sequencing datasets. The implementation of additional tools enables users to visualize and browse the complex, high-dimensional data now being generated in the reproductive field

TOXsIgN: a cross-species repository for toxicogenomic signatures

International audienceMOTIVATION:At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures.RESULTS:The TOXsIgN repository provides a flexible environment that facilitates online submission, storage and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses.AVAILABILITY AND IMPLEMENTATION:The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript and MongoDB, with all major browsers supported

Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole

International audienceExposure to endocrine-disrupting chemicals (EDCs) during development may cause reproductive disorders in women. Although female reproductive endpoints are assessed in rodent toxicity studies, a concern is that typical endpoints are not sensitive enough to detect chemicals of concern to human health. If so, measured endpoints must be improved or new biomarkers of effects included. Herein, we have characterized the dynamic transcriptional landscape of developing rat ovaries exposed to two well-known EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ), by 3’ RNA sequencing. Rats were orally exposed from day 7 of gestation until birth, and from postnatal day 1 until days 6, 14 or 22. Three exposure doses for each chemical were used: 3, 6 and 12 µg/kg bw/day of DES; 3, 6, 12 mg/kg bw/day of KTZ. The transcriptome changed dynamically during perinatal development in control ovaries, with 1137 differentially expressed genes (DEGs) partitioned into 3 broad expression patterns. A cross-species deconvolution strategy based on a mouse ovary developmental cell atlas was used to map any changes to ovarian cellularity across the perinatal period to allow for characterization of actual changes to gene transcript levels. A total of 184 DEGs were observed across dose groups and developmental stages in DES-exposed ovaries, and 111 DEGs in KTZ-exposed ovaries across dose groups and developmental stages. Based on our analyses, we have identified new candidate biomarkers for female reproductive toxicity induced by EDC, including Kcne2, Calb2 and Insl3

PFOS-induced thyroid hormone system disrupted rats display organ-specific changes in their transcriptomes

International audiencePerfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitarythyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption