Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues

Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local ‘differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling

Using bio.tools to generate and annotate workbench tool descriptions

Workbench and workflow systems such as Galaxy, Taverna, Chipster, or Common Workflow Language (CWL)-based frameworks, facilitate the access to bioinformatics tools in a user-friendly, scalable and reproducible way. Still, the integration of tools in such environments remains a cumbersome, time consuming and error-prone process. A major consequence is the incomplete or outdated description of tools that are often missing important information, including parameters and metadata such as publication or links to documentation. ToolDog (Tool DescriptiOn Generator) facilitates the integration of tools - which have been registered in the ELIXIR tools registry (https://bio.tools) - into workbench environments by generating tool description templates. ToolDog includes two modules. The first module analyses the source code of the bioinformatics software with language-specific plugins, and generates a skeleton for a Galaxy XML or CWL tool description. The second module is dedicated to the enrichment of the generated tool description, using metadata provided by bio.tools. This last module can also be used on its own to complete or correct existing tool descriptions with missing metadata

bio-tools/ToolDog: v0.3.3 for F1000 submission

Generating tool descriptors from bio.tool

Gene expression analysis in EBV-infected ataxia-telangiectasia cell lines by RNA-sequencing reveals protein synthesis defect and immune abnormalities

International audienceBackground Epstein–Barr virus (EBV) targets B-cells where it establishes a latent infection. EBV can transform B-cells in vitro and is recognized as an oncogenic virus, especially in the setting of immune compromise. Indeed, immunodeficient patients may fail to control chronic EBV infection, leading to the development EBV-driven lymphoid malignancies. Ataxia telangiectasia (AT) is a primary immune deficiency caused by mutations in the ATM gene, involved in the repair of double-strand breaks. Patients with AT are at high risk of developing cancers, mostly B-cell lymphoid malignancies, most of which being EBV-related. Aside from immune deficiency secondary to AT, loss of ATM function could also hinder the control of the virus within B-cells, favoring lymphomagenesis in AT patients. Results We used RNA sequencing on lymphoblastoid cell lines derived from patients with AT and healthy donors to analyze and compare both cellular and viral gene expression. We found numerous deregulated signaling pathways involving transcription, translation, oncogenesis and immune regulation. Specifically, the translational defect was confirmed in vitro, suggesting that the pathogenesis of AT may also involve a ribosomal defect. Concomitant analysis of viral gene expression did not reveal significant differential gene expression, however, analysis of EBV interactome suggests that the viral latency genes EBNA-3A, EBNA-3C and LMP1 may be disrupted in LCL from AT patients. Conclusion Our data support the notion that ATM deficiency deregulates cellular gene expression possibly disrupting interactions with EBV latent genes, promoting the oncogenic potential of the virus. These preliminary findings provide a new step towards the understanding of EBV regulation and of AT pathogenesis

Microbial diversity in the vaginal microbiota and its link to pregnancy outcomes

International audienceAbstract The vaginal microbiota refers to the microorganisms that reside in the vagina. These microorganisms contribute significantly to a woman’s reproductive and general health. A healthy vaginal microbiota is typically a low-diversity environment with a predominance of lactic acid-producing Lactobacillus species. Factors such as antibiotic use, sexual activity, and hormonal changes can disrupt the balance of the vaginal microbiota, leading to conditions such as bacterial vaginosis. The composition of the vaginal microbiota changes and takes on added importance during pregnancy, serving as a barrier against infection for both mother and fetus. Despite the importance of the microorganisms that colonize the vagina, details of how changes in composition and diversity can impact pregnancy outcomes is poorly understood. This is especially true for woman with a high prevalence of Gardnerella vaginalis . Here we report on a diverse cohort of 749 women, enrolled in the InSPIRe cohort, during their final trimester of pregnancy. We show that Lactobacilli , including L. crispatus are important in maintaining low diversity, and that depletion in this critical community is linked with preterm delivery. We further demonstrate that it is overall diversity of the vaginal microbiota, not specific species, which provides the best indicator of risk

ABRomics - a digital platform on antimicrobial resistance to store, integrate, analyze and share multi-omics data

International audienceAntibiotic resistance (ABR) is a major public health issue prioritized for mitigation by major international institutions, especially regarding the emergence and the global dissemination of multidrug resistant (MDR) isolates and of antibiotic resistance genes (ARGs) carried by mobile genetic elements. They are also transmitted between humans, animals and the environment, without borders. The evolution of ABR is a complex process with multiple selective forces in different environments.Genome sequences, which contain all the genetic information of an organism, can be used for molecular typing purposes with the highest resolution, the identification of ARGs and their genetic supports as well as mutations leading to a decrease in antibiotic susceptibility. Combined with epidemiological information, bacterial Whole Genome Sequencing (WGS) can enable tracking transmissions of outbreaks and identifying a source of contamination. Reinforcing the sharing of high-quality sequence data for diagnostic and epidemiological applications, together with interoperable and curated metadata, which can be integrated with other omics data, is a key requirement for understanding the complexity of spatiotemporal patterns of pathogen and ARGs transmission between compartments.Today, if more systematic genome sequencing and bioinformatics analysis can partially address such major issues, data sharing and comparison across centers, together with standardization of analytical workflows remain major bottlenecks. The ABRomics project aims to develop a secure One Health, online platform to make bacterial infectious disease (meta)genomics data and their associated clinical and epidemiological metadata accessible to a meta-network of researchers including epidemiologists, clinical microbiologists and the wider research community. It should provide the diverse communities with a user-friendly platform to store, share and analyze genomic information together with their metadata. It will also serve as a data brokering hub to ease the submission of data sequences into international repositories.The platform will meet two main objectives:1. Establish a repository of structured, interoperable, standardized, and well-annotated multi-omics microbiology data with tailored mathematical and bioinformatics tools that can be used to answer specific research questions related to ABR.2. Establish a shared platform to facilitate retrospective and prospective surveillance of ABRs in human and veterinary medicine, including environmental and food isolates, to enable near-real-time surveillance of pathogen transmission and outbreaks with actionable results for public health authorities. FAIR (Findable, Accessible, Interoperable and Reusable) data management procedures will enable retrospective studies.We will present here the ongoing development of the three main modules of the ABRomics platform architecture: (i) ABRomics-BIOINFO: an IT infrastructure with high capacity of data storage and data analysis, accessible to users under defined rules and offering a general software environment, both HPC and Cloud environments, (ii) ABRomics-DB: an integrated multi-omics microbiological databases for the Human-Animal-Environment sectors, and (iii) ABRomics-WF: standard tools and pipelines for (semi) automatic analysis of NGS data from pathogenic strains.The ABRomics project is led by the Institut Français de Bioinformatique (IFB), the Institut Pasteur and is made up of a consortium of 45 specialized teams belonging to the main French research organizations

ABRomics - an open access online platform on antimicrobial resistance to store, integrate, analyze and share multi-omics data

International audienceAntibiotic resistance (ABR) is a major public health issue prioritized for mitigation by international institutions. Multidrug resistant bacteria (MDRB) and Antibiotic Resistance Genes (ARGs) carried by mobile genetic elements spread between the human, animal, and environmental sectors. Whole Genome Sequencing (WGS) is used for molecular typing purposes at the highest resolution. It provides identification of ARGs and their genetic supports as well as mutations leading to a decrease in antibiotic susceptibility. Epidemiological and WGS data are used for tracking MDRB in hospital outbreaks but also across the animal and environmental sectors. Sharing and interoperability of high-quality data (sequence and metadata) are key requirements for addressing the spatio-temporal dissemination of MDRB. To this aim, the French Priority Plan on ABR has funded the development of an online, open platform dedicated to antibiotic resistance.We are establishing a repository of structured, interoperable, standardized, and well-annotated multi-omics data with tailored mathematical and bioinformatics tools to answer generic and specific research questions related to ABR. The ABRomics platform includes standardized pipelines to run ABR analyses of WGS from pathogenic strains supported with integrated databases (ARG, sequence types [ST], virulence factors [VF]). Uploading data, launching pipelines, viewing and cross-referencing enriched results will be achieved through easy-to-use web interfaces. ABRomics ß-version integrating the ABR detection genomic pipeline and other markers such as ST, and VF will be available in summer 2023. Core-genome multi-locus sequence typing, relationships between strains and metagenomics pipelines will next be made available

ABRomics - an open access online platform on antimicrobial resistance to store, integrate, analyze and share multi-omics data

International audienceAntibiotic resistance (ABR) is a major public health issue prioritized for mitigation by international institutions. Multidrug resistant bacteria (MDRB) and Antibiotic Resistance Genes (ARGs) carried by mobile genetic elements spread between the human, animal, and environmental sectors. Whole Genome Sequencing (WGS) is used for molecular typing purposes at the highest resolution. It provides identification of ARGs and their genetic supports as well as mutations leading to a decrease in antibiotic susceptibility. Epidemiological and WGS data are used for tracking MDRB in hospital outbreaks but also across the animal and environmental sectors. Sharing and interoperability of high-quality data (sequence and metadata) are key requirements for addressing the spatio-temporal dissemination of MDRB. To this aim, the French Priority Plan on ABR has funded the development of an online, open platform dedicated to antibiotic resistance.We are establishing a repository of structured, interoperable, standardized, and well-annotated multi-omics data with tailored mathematical and bioinformatics tools to answer generic and specific research questions related to ABR. The ABRomics platform includes standardized pipelines to run ABR analyses of WGS from pathogenic strains supported with integrated databases (ARG, sequence types [ST], virulence factors [VF]). Uploading data, launching pipelines, viewing and cross-referencing enriched results will be achieved through easy-to-use web interfaces. ABRomics ß-version integrating the ABR detection genomic pipeline and other markers such as ST, and VF will be available in summer 2023. Core-genome multi-locus sequence typing, relationships between strains and metagenomics pipelines will next be made available

ABRomics: An integrated multi-omics platform for antibiotic resistance research and public health

International audienceIntroduction and objectivesAntibiotic resistance (ABR) is a major public health issue prioritized for mitigation by international institutions. Multidrug resistant bacteria (MDRB) and Antibiotic Resistance Genes (ARGs) carried by mobile genetic elements spread between the human, animal, and environmental sectors. Whole Genome Sequencing (WGS) is used for molecular typing purposes at the highest resolution. It provides identification of ARGs and their genetic supports as well as mutations leading to a decrease in antibiotic susceptibility. Epidemiological and WGS data are used for tracking MDRB in hospital outbreaks but also across the animal and environmental sectors.Sharing and interoperability of high-quality data (sequence and metadata) are key requirements for addressing the spatio-temporal dissemination of MDRB. To this aim, the French Priority Plan on ABR has funded the development of an online, open platform dedicated to antibiotic resistance research and public health. MethodsWe are establishing a repository of structured, interoperable, standardized, and well-annotated multi-omics data with standard workflow analysis (Galaxy pipelines) to answer generic questions related to ABR, and tailored mathematical and bioinformatics tools to address more specific research questions. To access the platform, we are designing a web interface to also facilitate and combine the surveillance of ABR in the three sectors. FAIR (Findable, Accessible, Interoperable and Reusable) data management procedures will enable retrospective studies.The ABRomics platform is hosted at the French Bioinformatics Institute (www.francebioinformatique.fr) with a high capacity of analysis and 2 petabytes data storage.Results and conclusionsThe ABRomics platform includes standardized pipelines to run ABR analyses of WGS from pathogenic strains of interest for ABR, with integrated databases (ARG, sequence types [ST], virulence factors [VF]). Uploading data, launching pipelines, viewing and cross-referencing enriched results is achieved through easy-to-use web interfaces.ABRomics ß-version integrating the ABR detection genomic pipeline and other markers such as ST, and VF will be made available to the consortium in autumn 2023 and to the whole microbial research community in the beginning of 2024. Core-genome multi-locus sequence typing, relationships between strains and metagenomics pipelines will next be made available

ABRomics - an open access online platform on antimicrobial resistance to store, integrate, analyze and share multi-omics data

International audienceAntibiotic resistance (ABR) is a major public health issue prioritized for mitigation by international institutions. Multidrug resistant bacteria (MDRB) and Antibiotic Resistance Genes (ARGs) carried by mobile genetic elements spread between the human, animal, and environmental sectors. Whole Genome Sequencing (WGS) is used for molecular typing purposes at the highest resolution. It provides identification of ARGs and their genetic supports as well as mutations leading to a decrease in antibiotic susceptibility. Epidemiological and WGS data are used for tracking MDRB in hospital outbreaks but also across the animal and environmental sectors. Sharing and interoperability of high-quality data (sequence and metadata) are key requirements for addressing the spatio-temporal dissemination of MDRB. To this aim, the French Priority Plan on ABR has funded the development of an online, open platform dedicated to antibiotic resistance.We are establishing a repository of structured, interoperable, standardized, and well-annotated multi-omics data with tailored mathematical and bioinformatics tools to answer generic and specific research questions related to ABR. The ABRomics platform includes standardized pipelines to run ABR analyses of WGS from pathogenic strains supported with integrated databases (ARG, sequence types [ST], virulence factors [VF]). Uploading data, launching pipelines, viewing and cross-referencing enriched results will be achieved through easy-to-use web interfaces. ABRomics ß-version integrating the ABR detection genomic pipeline and other markers such as ST, and VF will be available in summer 2023. Core-genome multi-locus sequence typing, relationships between strains and metagenomics pipelines will next be made available