Project description:Inferring in humans biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to M-^StranslateM-^T the results to humans. In this context, the Systems Biology Verification for Industrial Methodology for Process Verification in Research (SBV IMPROVER) initiative had run a Species Translation Challenge for the scientific community to explore and understand the limit of translatability from rodent to human using systems biology. Therefore, a multi-layer omics dataset was generated that comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, the generation, processing and quality control analysis of the multi-layer omics dataset. The datasets are accessible in public repositories could be leveraged for further translation studies.
Project description:Immune tolerance is involved physiologically in pregnancy and disrupted in autoimmunity, organ rejection, and graft-versus-host disease (GvHD). In transplantation setting, operational tolerance has been inferred in patients who develop tolerance without a need for immunosuppressants. However, mechanisms underlying operational tolerance in Humans are poorly understood. Using two cohorts of patients who underwent an allo-HSCT from HLA-identical siblings, we used multi-omics approach to decipher immune landscape associated with tolerance in recipients and their related donors. We analyzed two cohorts of patients, one monocentric from Saint Louis hospital (cohort 1, n=41) and one multicenric from the national Cryostem consortium biological collection (cohort 2, n=69). We proceed to deep immunophenotyping of peripheral blood mononuclear cell using mass cytometry, RNA sequencing analysis and metabolomics profiling of plasma in both recipients and related donors. The aim of this study is to determine the evolution of immune landscape after allogeneic HSCT by comparison with healthy donors, and to identify specific biological mechanism associated with immune tolerance in patients.
Project description:Multi-omics single-cell profiling of surface proteins, gene expression and lymphocyte immune receptors from hospitalised COVID-19 patient peripheral blood immune cells and healthy controls donors. Identification of the coordinated immune cell compositional and state changes in response to SARS-CoV-2 infection or LPS challenge, compared to healthy control immune cells.
Project description:The gut microbiome plays a crucial role in modulating human immunity. Previously, we found that antibiotic-induced microbiome perturbation affected influenza vaccine responses depending on pre-existing immunity levels. However, its impact on primary responses remains unclear. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration disrupted the microbiome, reducing gut bacterial load and causing long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced: 1) an enhanced pro-inflammatory signature early after vaccination, 2) a shift in the balance of vaccine-specific T-helper 1(Th1) to T-follicular-helper response towards Th1 phenotype, 3) profound alterations in metabolites, particularly in secondary bile acids in blood. By integrating multi-omics datasets, we generated a multi-scale, multi-response network that revealed key regulatory nodes including the microbiota, secondary bile acids, and humoral immunity to vaccination.
Project description:Streptococcus suis is one of the most important bacterial pathogens of pigs, it is also an important zoonotic pathogen. It can withstand environmental stress and respond rapidly to stress. However, the regulatory mechanisms involved in this process are not fully elucidated. MnmE is a multi-domain GTPase that is highly conserved in bacteria and eukaryotes, driving tRNA modification during translation. In this study, we constructed an mnmE deletion strain (ΔmnmE) and a complementary strain (CΔmnmE) using the wild-type strain 05ZYH33 of S. suis, and systematically studied the characteristics and functions of MnmE in S. suis through phenotypic and multi-omics analyses. Phenotypic analysis showed that the mnmE strain exhibited growth defects, reduced virulence, decreased environmental tolerance, reduced capacity for metal ion transport, and changes in protein synthesis capabilities. Multi-omics results indicated that cellular processes related to carbohydrate metabolism, transcription and translation, and inorganic ion transport and metabolism were affected, which corroborated the phenotypic analysis.
Project description:Severe SARS-CoV-2 infection causes COVID-19. The host response to SARS-CoV-2 is poorly understood partly due to a lack of an animal model that recapitulates severe manifestations of human disease. Here we report a Syrian hamster model that develops a rapidly progressive lethal pulmonary disease that closely mimics human severe COVID-19. We evaluated host responses to infection using a multi-omics, multi-organ approach to define kinetic changes to the proteome, the phospho-proteome, and the transcriptome. These data revealed a robust antiviral response composed of both Type I and Type II interferon responses at the gene and protein levels. Both IFN and TNF-a responses were associated with peak viral replication at day 2 post-infection. These responses correlated to rapidly developing diffuse alveolar destruction and pneumonia that persisted in the absence of active viral infection. Extrapulmonary viral replication was detected in the heart and kidneys, which correlated with proteome and phospho-proteome remodeling in each organ. In addition to early antiviral responses, there was a significant and progressive increase in chemokines, monocyte, and neutrophil-associated molecules throughout the course of infection that peaked in the later time points. Together, our results provide a kinetic overview of multi-organ host responses to severe SARS-CoV-2 infection in vivo.
Project description:Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-κB-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria
Project description:Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-κB-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 8 healthy individuals after oral intake of three different growth stages of Lactobacillus plantarum or placebo control. In total, this study includes data from 8 individuals x 4 treatments=32 arrays.
Project description:Today, swine is regarded as promising biomedical model, however, its gastrointestinal microbiome dynamics have been less investigated than that of humans or murine models . The aim of this study was to establish a high-throughput multi-omics pipeline to investigate the healthy fecal microbiome of swine and its temporal dynamics as basis for future infection studies. To this end, a homogenization protocol based on deep-frozen feces followed by integrated sample preparation for different meta-omics analyses was developed. Subsequent data integration linked microbiome composition with function, i.e. expressed proteins and secreted metabolites.
Project description:We have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Plasma and serum from a virus infected timepoint (in triplicate) and 34 healthy contorl samples were collected and used to probe Invitrogen human protoarray v5.0.