Unknown,Transcriptomics,Genomics,Proteomics

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Gene networks associated with conditional fear in mice identified using a systems genetics approach

ABSTRACT: To uncover genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. We mapped 27 behavioral quantitative trait loci with a false discovery rate of 5%. We also identified two gene co-expression networks correlated with context-dependent immobility. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. We surveyed the architecture of brain transcript regulation and showed preservation of gene co-expression modules in hippocampus and striatum while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance associated strongly with fear phenotypes. Total mRNA islolated from hippocampus and striatum of strains from Hybrid Mouse Diversity Panel and gene expression quantified using Illumina MouseRef-8 v2.0 microarrays. Submission includes gene expression data from 100 strains of HMDP for hippocampus (n=1 for each strain) and 98 strains of HMDP for striatum (n=1 for each strain).

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Park

PROVIDER: E-GEOD-26500 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines. 64 samples of IL4 DC, and 64 samples of monocytes stimulated by media (controls, designated 1 and 2 to indicate biological replicates), Menomune (Neisseiria meningitis vaccine, MGL), Fluzone 09-10 (Influenza vaccine, FZ), Havrix (Hepatitis A vaccine, HEPA), Ixiaro (Japanese encephalitis vaccine, JPE), ActHib (Haemophilus influenza vaccine, HIB) and Pneumovax (Pneumococcus vaccine, PVX), Engerix-B (Hepatitis B vaccine, HEPB), Zostavax (Herpes Zoster vaccine, HER), and Gardasil (Human Papilloma virus vaccine, HPV), LPS, Ipol (Polio vaccine, POL), Rabies vaccine (RAB), toxoid-based vaccine (TDAP), Varivax (Varicella vaccine, VAR)

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Gene networks associated with conditional fear in mice identified using a systems genetics approach

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