Immune Cell Line Mixtures
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE11058 | GEO | 2009/07/07
SECONDARY ACCESSION(S): PRJNA108813
REPOSITORIES: GEO
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Project description:Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. Its ability to discriminate related human cells is unknown. Here we test the ability of this technique to determine the fractions of transformed cells of immune origin in mixed samples. Experiment Overall Design: Four immune cell lines were grown and run on microarrays either by themselves or in mixtures of various relative proportions. Mixtures of cells were performed in triplicate. Experiment Overall Design: MixA (Jurkat: 2.5, IM-9: 1.25, Raji: 2.5, THP-1: 3.75) Experiment Overall Design: MixB (Jurkat: 0.5, IM-9: 3.17, Raji: 4.75, THP-1: 1.58) Experiment Overall Design: MixC (Jurkat: 0.1, IM-9: 4.95, Raji: 1.65, THP-1: 3.3) Experiment Overall Design: MixD (Jurkat: 0.02, IM-9: 3.33, Raji: 3.33, THP-1: 3.33)
2009-07-19 | E-GEOD-11058 | biostudies-arrayexpress
Project description:Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples. Here we test the ability of this technique to determine the fractions of subsets of memory T cells in peripheral blood mononuclear cell (PBMC) samples. Keywords: cell type comparison
2009-07-07 | GSE11057 | GEO
Project description:Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples. Here we test the ability of this technique to determine the fractions of subsets of memory T cells in peripheral blood mononuclear cell (PBMC) samples. Experiment Overall Design: PBMC samples from several donors were split. One portion of each PBMC sample was set aside, while the remainder of each was sorted into naive, central memory, and effector memory T cell subsets.
2009-07-19 | E-GEOD-11057 | biostudies-arrayexpress
Project description:Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogeneous biospecimens such as whole blood, offer a promising solution. However, their performance depends entirely on the library of DNA methylation markers being used as the basis for deconvolution. The objective of this study was to train and validate an algorithm for the identification of optimal DNA methylation libraries for the deconvolution of adult human whole blood.
2016-02-12 | GSE77797 | GEO
Project description:Small organisms can be used as biomonitoring tools to assess chemicals in the environment. Chemical stressors are especially hard to assess and monitor when present as complex mixtures. Here, Daphnia magna were exposed for 24 hours to five different munitions constituents 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), trinitrobenzene (TNB), dinitrobenzene (DNB), or 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) as well as to 8 different munitions mixtures and ground water contaminated with munitions constituents. To better understand possible mixture effects, gene expression changes from all treatments were compared using high-density microarrays. While mixtures and ground water exposures had genes and gene functions in common with single chemical exposures, unique functions were also affected, which was consistent with the non-additivity of chemical effects in these mixtures.
2011-06-23 | GSE30163 | GEO
Project description:The cellular composition of heterogeneous samples can be predicted from reference gene expression profiles that represent the homogeneous, constituent populations of the heterogeneous samples. However, existing methods fail when the reference profiles are not representative of the constituent populations. We developed PERT, a new probabilistic expression deconvolution method, to address this limitation. PERT was used to deconvolve cellular composition of variably sourced and treated heterogeneous human blood samples. Our results indicate that even after correcting batch effects, cells presenting the same cell surface antigens display different transcriptional programs when they are uncultured versus culture-derived. Given gene expression profiles of culture-derived heterogeneous samples and profiles of uncultured reference populations, PERT was able to accurately recover proportions of pure populations composing the heterogeneous samples. We anticipate that PERT will be widely applicable to expression deconvolution problems using profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular identity. Gene expression microarray to examine transcriptome variations between uncultured and culture-deried blood cells of the same phenotype as defined by the on and off expression of antigens. Fresh human umbilical cord blood-derived and serum free culture-derived colony-forming unit-monocytes (CFU-M) and megakaryocytes (MEGA) were compared respectively
2012-09-13 | E-GEOD-40830 | biostudies-arrayexpress
Project description:Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogeneous biospecimens such as whole blood, offer a promising solution. However, their performance depends entirely on the library of DNA methylation markers being used as the basis for deconvolution. The objective of this study was to train and validate an algorithm for the identification of optimal DNA methylation libraries for the deconvolution of adult human whole blood. Purified granulocytes, monocytes, CD4T, CD8T, natural killer cells, and B cells from normal human subjects were purchased from AllCells LLC (Emeryville, CA). DNA extracted from purified leukocyte subtypes were mixed in predetermined proportions to reconstruct two distinct sets of white blood cell (WBC) mixtures, each consisting of six samples. An additional six whole blood (WB) samples from disease-free adult donors with available immune cell profiling data from flow cytometry were purchased from All-Cells LLC and were included in this investigation. All DNA samples were bisulfite modified using the Zymo EZ DNA Methylation kit (Irvine, CA) and profiled for DNA methylation using the Illumina HumanMethylation450 array platform.
2016-02-12 | E-GEOD-77797 | biostudies-arrayexpress
Project description:Abstract — Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48 h) larval fathead minnow (Pimephales promelas) exposures. IMX-101 consists of a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) while IMX-104 is composed of DNAN, NTO, and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). DNAN was the most potent constituent in IMX-101 eliciting an LC50 of 36.1 mg/L, whereas NTO and NQ did not elicit significant mortality in exposures up to 1040 and 2640 mg/L, respectively. Toxic unit calculations indicated that IMX-101 elicited toxicity representative of the component concentration of DNAN within the mixture. Toxicogenomic responses for the individual constituents of IMX-101 indicated unique transcriptional expression and functional responses characteristic of: oxidative stress, impaired energy metabolism, tissue damage and inflammatory responses in DNAN exposures; impaired steroid biosynthesis and developmental cell-signaling in NQ exposures; and altered mitogen-activated protein kinase signaling in NTO exposures. Transcriptional responses to the IMX-101 mixture were driven by the effects of DNAN where expression and functional responses were nearly identical comparing DNAN alone versus the fractional equivalent of DNAN within IMX-101. Given that each individual constituent of the IMX-101 mixture elicited unique functional responses, and NTO and NQ did not interact with DNAN within the IMX-101 mixture exposure, the overall toxicity and toxicogenomic responses within acute exposures to the IMX-101 formulation are indicative of "independent" mixture toxicology. Alternatively, in the IMX-104 exposure both DNAN and RDX were each present at concentrations sufficient to elicit lethality (RDX LC50 = 28.9 mg/L). Toxic-unit calculations for IMX-104 mixture formulation exposures indicated slight synergistic toxicity (ΣTU LC50 = 0.82, 95% confidence interval = 0.73-0.90). Unique functional responses relative to DNAN were observed in the IMX-104 exposure including responses characteristic of RDX exposure. Based on previous transcriptomics responses to acute RDX exposures in fathead minnow larvae, we hypothesize that the potentially synergistic responses within the IMX-104 mixture are related to interactive effects of each DNAN and RDX on oxidative stress mitigation pathways.
2018-03-01 | GSE101887 | GEO
Project description:Abstract — Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48 h) larval fathead minnow (Pimephales promelas) exposures. IMX-101 consists of a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) while IMX-104 is composed of DNAN, NTO, and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). DNAN was the most potent constituent in IMX-101 eliciting an LC50 of 36.1 mg/L, whereas NTO and NQ did not elicit significant mortality in exposures up to 1040 and 2640 mg/L, respectively. Toxic unit calculations indicated that IMX-101 elicited toxicity representative of the component concentration of DNAN within the mixture. Toxicogenomic responses for the individual constituents of IMX-101 indicated unique transcriptional expression and functional responses characteristic of: oxidative stress, impaired energy metabolism, tissue damage and inflammatory responses in DNAN exposures; impaired steroid biosynthesis and developmental cell-signaling in NQ exposures; and altered mitogen-activated protein kinase signaling in NTO exposures. Transcriptional responses to the IMX-101 mixture were driven by the effects of DNAN where expression and functional responses were nearly identical comparing DNAN alone versus the fractional equivalent of DNAN within IMX-101. Given that each individual constituent of the IMX-101 mixture elicited unique functional responses, and NTO and NQ did not interact with DNAN within the IMX-101 mixture exposure, the overall toxicity and toxicogenomic responses within acute exposures to the IMX-101 formulation are indicative of "independent" mixture toxicology. Alternatively, in the IMX-104 exposure both DNAN and RDX were each present at concentrations sufficient to elicit lethality (RDX LC50 = 28.9 mg/L). Toxic-unit calculations for IMX-104 mixture formulation exposures indicated slight synergistic toxicity (ΣTU LC50 = 0.82, 95% confidence interval = 0.73-0.90). Unique functional responses relative to DNAN were observed in the IMX-104 exposure including responses characteristic of RDX exposure. Based on previous transcriptomics responses to acute RDX exposures in fathead minnow larvae, we hypothesize that the potentially synergistic responses within the IMX-104 mixture are related to interactive effects of each DNAN and RDX on oxidative stress mitigation pathways.
2018-03-01 | GSE101886 | GEO
Project description:Abstract — Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48 h) larval fathead minnow (Pimephales promelas) exposures. IMX-101 consists of a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) while IMX-104 is composed of DNAN, NTO, and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). DNAN was the most potent constituent in IMX-101 eliciting an LC50 of 36.1 mg/L, whereas NTO and NQ did not elicit significant mortality in exposures up to 1040 and 2640 mg/L, respectively. Toxic unit calculations indicated that IMX-101 elicited toxicity representative of the component concentration of DNAN within the mixture. Toxicogenomic responses for the individual constituents of IMX-101 indicated unique transcriptional expression and functional responses characteristic of: oxidative stress, impaired energy metabolism, tissue damage and inflammatory responses in DNAN exposures; impaired steroid biosynthesis and developmental cell-signaling in NQ exposures; and altered mitogen-activated protein kinase signaling in NTO exposures. Transcriptional responses to the IMX-101 mixture were driven by the effects of DNAN where expression and functional responses were nearly identical comparing DNAN alone versus the fractional equivalent of DNAN within IMX-101. Given that each individual constituent of the IMX-101 mixture elicited unique functional responses, and NTO and NQ did not interact with DNAN within the IMX-101 mixture exposure, the overall toxicity and toxicogenomic responses within acute exposures to the IMX-101 formulation are indicative of "independent" mixture toxicology. Alternatively, in the IMX-104 exposure both DNAN and RDX were each present at concentrations sufficient to elicit lethality (RDX LC50 = 28.9 mg/L). Toxic-unit calculations for IMX-104 mixture formulation exposures indicated slight synergistic toxicity (ΣTU LC50 = 0.82, 95% confidence interval = 0.73-0.90). Unique functional responses relative to DNAN were observed in the IMX-104 exposure including responses characteristic of RDX exposure. Based on previous transcriptomics responses to acute RDX exposures in fathead minnow larvae, we hypothesize that the potentially synergistic responses within the IMX-104 mixture are related to interactive effects of each DNAN and RDX on oxidative stress mitigation pathways.
2018-03-01 | GSE101870 | GEO