Project description:<p><strong>AIMS: </strong>Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.</p><p><strong>METHODS:</strong> In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10).</p><p><strong>RESULTS:</strong> During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.</p><p><strong>CONCLUSIONS:</strong> Our data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.</p><p><br></p><p><strong>Links: </strong></p><p>The GEMs for PBMCs have been submitted to <a href='https://www.ebi.ac.uk/biomodels/MODEL1905270001' rel='noopener noreferrer' target='_blank'>BioModels</a>, under accession number MODEL1905270001.</p>
Project description:Effect of Gpnmb knockout on development of differential expression in PFF-aSyn model was studied. The "sample_id" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0036142
Project description:Effect of Gpnmb knockout on development of differential expression in AAV-aSyn model was studied. The "samid" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0036339
Project description:Using renal ischemia-reperfusion injury as a model of acute kidney injury, we deteremined temporally-released miRNAs released in urinary exosomes during the injury
Project description:Gene-expression microarray datasets generated as part of the Immunological Genome Project (ImmGen). Primary cells from multiple immune lineages are isolated ex-vivo, primarily from young adult B6 male mice, and double-sorted to >99% purity. RNA is extracted from cells in a centralized manner, amplified and hybridized to Affymetrix 1.0 ST MuGene arrays. Protocols are rigorously standardized for all sorting and RNA preparation. Data is released monthly in batches of cell populations. This Series record provides access to Immunological Genome Project data submitted to GEO.
Project description:Influenza A Virus (IAV) is a recurring respiratory virus with antiviral therapies of limited use. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses with three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we mapped 332 IAV-human protein-protein interactions and identified 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza revealed several genes, including the structural scaffold protein AHNAK, with predicted loss-of-function variants that were also identified in our proteomic analyses. Of our identified host factors, 54 significantly altered IAV infection upon siRNA knockdown, and two factors, COPB1 and AHNAK, were also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppressed IAV replication, with three targeting ATP6V1A, CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. This project includes the global proteomic data (abundance and phosphorylation), the AP-MS data has been submitted separately as its own dataset and has its own dataset identifier.
Project description:Influenza A Virus (IAV) is a recurring respiratory virus with antiviral therapies of limited use. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses with three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we mapped 332 IAV-human protein-protein interactions and identified 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza revealed several genes, including the structural scaffold protein AHNAK, with predicted loss-of-function variants that were also identified in our proteomic analyses. Of our identified host factors, 54 significantly altered IAV infection upon siRNA knockdown, and two factors, COPB1 and AHNAK, were also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppressed IAV replication, with three targeting ATP6V1A, CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. This project includes the AP-MS data; all global proteomic data (abundance and phosphorylation) has been submitted separately as its own dataset and has its own dataset identifier.
Project description:Gene Expression profiles from whole cortical tissue from the PS2APP transgenic mouse model of Alzheimer's disease will reflect the cellular alterations, including the pathological drivers and the compensatory mechanisms of neurodegeneration when compared to wild-type control animals. The "SAMID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0006684 Keywords: Expression profiling by array