Abstract
Large-scale genotype and phenotype data have been increasingly generated to identify genetic markers, understand gene function and evolution and facilitate genomic selection. These datasets ...hold immense value for both current and future studies, as they are vital for crop breeding, yield improvement and overall agricultural sustainability. However, integrating these datasets from heterogeneous sources presents significant challenges and hinders their effective utilization. We established the Genotype-Phenotype Working Group in November 2021 as a part of the AgBioData Consortium (https://www.agbiodata.org) to review current data types and resources that support archiving, analysis and visualization of genotype and phenotype data to understand the needs and challenges of the plant genomic research community. For 2021–22, we identified different types of datasets and examined metadata annotations related to experimental design/methods/sample collection, etc. Furthermore, we thoroughly reviewed publicly funded repositories for raw and processed data as well as secondary databases and knowledgebases that enable the integration of heterogeneous data in the context of the genome browser, pathway networks and tissue-specific gene expression. Based on our survey, we recommend a need for (i) additional infrastructural support for archiving many new data types, (ii) development of community standards for data annotation and formatting, (iii) resources for biocuration and (iv) analysis and visualization tools to connect genotype data with phenotype data to enhance knowledge synthesis and to foster translational research. Although this paper only covers the data and resources relevant to the plant research community, we expect that similar issues and needs are shared by researchers working on animals.
Database URL: https://www.agbiodata.org.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Antigen-specific CD4 and CD8 T cells are important components of the immune response to
, yet little information is currently known regarding how the breadth, specificity, phenotype, and function of
...-specific T cells correlate with
infection outcome in humans. To facilitate evaluation of human
-specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60
Ags. Using IFN-γ production as a readout of Ag specificity, the assay can be conducted using 50 μl of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of
-unexposed healthy adults, foreign-born adults with latent
infection residing in the United States, and tuberculosis household contacts with latent
infection in a tuberculosis-endemic setting in Kenya. The
-specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating
-specific T cell responses across different states of
infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of
-specific T cell responses associated with
infection outcomes.
Abstract
Tuberculosis (TB) is among the leading causes of death worldwide. While IFN-γ and CD4+ Th1 T cell responses are necessary to mount an immune response to Mycobacterium tuberculosis (Mtb), the ...causative agent of TB, they are not sufficient to provide protection. Studies from several groups, including our own, have highlighted an important role for IL-17 and Th17 responses in immunity to Mtb infection. Previous research from the laboratory has shown that Mtb restricts Th17 responses by dampening dendritic cell (DC) responses and has identified CD40-mediated co-stimulation as critical for generating Th17 responses in response to Mtb. We showed that exogenous CD40 engagement on Mtb-infected DCs enhances Th17 polarization and reduces Mtb burden in the lungs in a vaccination model. However, the DC mechanisms that mediate CD40-dependent Th17 polarization and protection have not been defined. Here we show that Notch signaling in DCs modulates DC-T cell crosstalk and influences T cell polarization during infection. Engaging the CD40 pathway on Mtb-infected DCs increases the mRNA and protein expression of Notch ligands DLL4 and Jagged1 over the course of infection. Blockade of Jagged1 during a DC-T cell co-culture lowers Th1 responses while blockade of both DLL4 and Jagged1 significantly limits Th17 polarization. These results reveal that during infection, Mtb restricts expression of Notch ligands, which impedes Th17 responses during TB. Insights from this study could be applied to designing more efficacious TB vaccines and adjuvants.
Antigen (Ag)-specific CD4 and CD8 T cells are important components of the
immune response to
Mycobacterium tuberculosis
(Mtb), yet little
information is currently known regarding how the breadth, ...specificity, phenotype
and function of Mtb-specific T cells correlate with Mtb infection outcome in
humans. To facilitate evaluation of human Mtb-specific T cell responses
targeting multiple different Ags, we sought to develop a high throughput and
reproducible T cell response spectrum assay (RSA) requiring low blood sample
volumes. We describe here the optimization and standardization of a microtiter
plate-based, diluted whole blood stimulation assay utilizing overlapping peptide
pools corresponding to a functionally diverse panel of 60 Mtb Ags. Using
IFN-γ production as a readout of Ag specificity, the assay can be
conducted using 50µl of blood per test condition and can be expanded to
accommodate additional Ags. We evaluated the intra- and inter-assay variability,
and implemented testing of the assay in diverse cohorts of Mtb-unexposed healthy
adults, foreign-born adults with latent Mtb infection (LTBI) residing in the
U.S., and TB household contacts with LTBI in a TB-endemic setting in Kenya. The
Mtb-specific T cell RSA further enhances the immunological toolkit available for
evaluating Mtb-specific T cell responses across different states of Mtb
infection, and can be readily implemented in resource limited settings.
Moreover, application of the assay to longitudinal cohorts will facilitate
evaluation of treatment- or vaccine-induced changes in the breadth and
specificity of Ag-specific T cell responses, as well as identification of
Mtb-specific T cell responses associated with Mtb infection outcomes.
Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated ...three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum.
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•Somatic GBM mouse models were developed to compare tumor bulk and margin biology•GBM cell fates are imposed by tumor region independent of driver mutations•T cell-induced dormancy prevails in bulk, astrocyte-like differentiation in margin•Bulk and margin cells are functionally distinct subpopulations
Garcia-Diaz et al. develop immunocompetent and disease-relevant somatic mouse models of glioblastoma to reveal that tumor bulk and margin cells have distinct biology, including differences in dormancy, differentiation trajectories, immune recruitment, and invasive and tumorigenic potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Globally, soils store two to three times as much carbon as currently resides in the atmosphere, and it is critical to understand how soil greenhouse gas (GHG) emissions and uptake will respond to ...ongoing climate change. In particular, the soil‐to‐atmosphere CO2 flux, commonly though imprecisely termed soil respiration (RS), is one of the largest carbon fluxes in the Earth system. An increasing number of high‐frequency RS measurements (typically, from an automated system with hourly sampling) have been made over the last two decades; an increasing number of methane measurements are being made with such systems as well. Such high frequency data are an invaluable resource for understanding GHG fluxes, but lack a central database or repository. Here we describe the lightweight, open‐source COSORE (COntinuous SOil REspiration) database and software, that focuses on automated, continuous and long‐term GHG flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation. Contributed datasets are mapped to a single, consistent standard, with metadata on contributors, geographic location, measurement conditions and ancillary data. The design emphasizes the importance of reproducibility, scientific transparency and open access to data. While being oriented towards continuously measured RS, the database design accommodates other soil‐atmosphere measurements (e.g. ecosystem respiration, chamber‐measured net ecosystem exchange, methane fluxes) as well as experimental treatments (heterotrophic only, etc.). We give brief examples of the types of analyses possible using this new community resource and describe its accompanying R software package.
Here we describe the lightweight, open source COSORE (COntinuous SOil REspiration) database and software. COSORE focuses on automated, continuous and long‐term greenhouse gas flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The anti-apoptotic function and tumor-associated expression of heat-shock protein 70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote tumorigenesis. However, its ...immunomodulatory activities to induce anti-tumor immunity predict the suppression of tumor growth. Using the Hsp70.1/3(-/-)(Hsp70(-/-)) mouse model, we observed that tumor-derived HSP70 was neither required for cellular transformation nor for in vivo tumor growth. Hsp70(-/-) murine embryonic fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison of Bcr-Abl-mediated transformation of WT and Hsp70(-/-) bone marrow and progression of B-cell leukemogenesis in vivo revealed no differences in disease onset or survival rates, and Eμ-Myc-driven lymphoma in Hsp70(-/-) mice was phenotypically indistinguishable from that in WT Eμ-Myc mice. However, Hsp70(-/-) E1A/Ras MEFs generated significantly larger tumors than their WT counterparts in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in intra-tumoral infiltration of innate and adaptive immune cells, including macrophages and CD8(+) T cells. Evaluation of several potential mechanisms revealed an HSP70-chemokine-like activity to promote cellular migration. These observations support a role for tumor-derived HSP70 in facilitating anti-tumor immunity to limit tumor growth and highlight the potential consequences of anti-HSP70 therapy as an efficacious anti-cancer strategy.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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