Dynamic profiling of the protein life cycle in response to pathogens (RNA-seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Aviv Regev
PROVIDER: E-GEOD-59784 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Protein expression is regulated by production and degradation of mRNAs and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics to build a quantitative genomic model of the differential regulation of gene expression in LPS stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for over half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction of novel cellular functions and remodeling of preexisting functions through the protein life cycle. Mouse primary dendritic cells were treated with LPS or mock stimulus and profiled over a 12-hour time course. Cells were grown in M-labeled SILAC media, which was replaced with H-labeled SILAC media at time 0. Aliquots were taken at 0, 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 hours post-stimulation and added to equal volumes of a master mix of unlabeled (L) cells for the purpose of normalization. RNA-Seq was performed at 0, 1, 2, 4, 6, 9, and 12 hours post-stimulation.
2015-03-06 | E-GEOD-59792 | biostudies-arrayexpress
Project description:Malaria represents a major public health problem in Africa [1]. In the East African highlands, even in high-altitude areas previously considered too cold to support vector population and parasite transmission [2], frequent malaria epidemics have been reported since the 1980M-bM-^@M-^Ys [3]. Plasmodium falciparum infections have been detected in areas as high as 1,600-2,400m above sea level in Africa [4], albeit there is a marked gradient of parasite prevalence along the altitude transect [5-7]. Both the historical absence of malaria in the African highlands and now the intensive malaria control efforts put in place after the recent outbreaks have reduced malaria prevalence and incidence [8], rendering the East African highlands particularly prone to epidemic malaria due to the lack of the protective immunity, and causing significant human mortality amongst all age groups [9]. Therefore, malaria transmission monitoring in the East African highlands becomes a particularly important public health issue.Despite the overall lower immunity of the population in these historically malaria-free areas, the many successive outbreaks since the 1980M-bM-^@M-^Ys may have generated some level of immunity against P. falciparum amongst highland residents. The antibody response to Plasmodium is cumulative and long lasting, developing after repeated exposures to the parasite and persisting for months or years after infection was resolved. The antibody response to Plasmodium varies amongst individuals of different age groups (i.e. toddlers, children and adults) as well as amongst individuals of same age groups from areas of different parasite prevalence [10]. The repertoire of targets of the antibody response also expands after multiple infections, with the number of recognized antigens being correlated to parasite prevalence, age and immunity to clinical malaria [11,12]. Serological studies bring forth indirect evidence of human exposure to the parasite, and can reliably assess its prevalence and transmission intensity in an endemic area [13-15]. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasiteM-bM-^@M-^Ys antigens. The work we present here is an expansion of the study published by Badu et al. [16], in which the antibody response to the 19kDa fragment of merozoite surface protein 1 (MSP-119) was examined in populations from two endemic areas in the western Kenyan highlands. There, the tremendous variations of malaria transmission intensity in a small spatial scale are caused by substantial differences in altitude, topography and other environmental conditions [6,7,17,18]. We now expand our antibody profiling survey to include 854 P. falciparum proteins by using high-throughput proteomic microarray technology. Protein microarrays have been used to explore the humoral response to P. falciparum in other African settings [19-24], but this is the broadest characterization of the antibody responses of the population of western Kenyan highlands to date. In the present study we: i) determined the serological reactivity against P. falciparum (Pf) in subjects residing in a low transmission area, and detected hotspots of transmission; ii) examined the dynamics of antibody response to hundreds of Pf proteins generated by sera from toddlers, older children and adults residing in two endemic areas differing in transmission intensities, during two distinct malaria seasons, and compared the intensity, breadth and antigenic targets of these responses; and iii) identified candidate Pf antigenic markers that could provide more sensitive serological surveillance to detect micro-geographic variations in malaria transmission levels and differentiate hotspots of infection in low endemic areas. (references provided in the 'readme.txt') Antibody profiling was performed on sera from residents of western Kenyan highlands against Plasmodium falciparum. One-hundred and ten age-stratified serum samples collected during the dry and the wet seasons, from residents of two locations with differing parasite transmission levels (uphill and valley bottom), and 10 unexposed USA controls were probed on a protein microarray displaying 854 unique proteins of P. falciparum.
2013-06-20 | E-GEOD-48089 | biostudies-arrayexpress
Project description:The yeast Dekkera bruxellensis is as ethanol tolerant as Saccharomyces cerevisiae and may be found in bottled wine. It causes the spoilage of wine, beer, cider and soft drinks. In wines, the metabolic products responsible for spoilage by Dekkera bruxellensis are mainly volatile phenols. These chemical compounds are responsible for the taints described as M-bM-^@M-^XM-bM-^@M-^XmedicinalM-bM-^@M-^YM-bM-^@M-^Y in white wines (due to vinyl phenols) and as M-bM-^@M-^XM-bM-^@M-^XleatherM-bM-^@M-^YM-bM-^@M-^Y, M-bM-^@M-^XM-bM-^@M-^Xhorse sweatM-bM-^@M-^YM-bM-^@M-^Y and M-bM-^@M-^XM-bM-^@M-^XstableM-bM-^@M-^YM-bM-^@M-^Y in red wines (due to ethyl phenols mainly 4-ethylphenol). Apart from the negative aroma nuances imparted by these yeasts, positive aromas such as M-bM-^@M-^XsmokyM-bM-^@M-^Y, M-bM-^@M-^XspicyM-bM-^@M-^Y and M-bM-^@M-^XtoffeeM-bM-^@M-^Y are also cited. Our goal was to identify the impact that the wine spoilage yeast Dekkera bruxellensis has on fermenting S. cerevisiae cells, especially on its gene expression level. To this end we co-inoculated both yeast species at the start of fermentation in a synthetic wine must, using S. cerevisiae-only fermentations without Dekkera bruxellensis as a control. All fermentations were employed in special membrane reactors (50 KDa pore size cut-off) physically separating Dekkera bruxellensis from wine yeast S. cerevisiae. Biomass separation with this membrane was done to abolish the possibility of hybridizing also D. bruxellensis probes on Agilent V2 (8x15K format) G4813 DNA microarrays designed just for S. cerevisiae ORF targets. The 50 KDa pore membrane separating both yeasts allowed the exchange of ethanol, metabolites and sugars during the fermentation. Fermentations were carried out in synthetic wine must in duplicate for both the control S. cerevisiae (strain Lalvin EC1118) and mixed fermentation. Sampling of yeast S. cerevisiae for RNA extractions were performed at 22 h of fermentation, during the exponential growth phase of S. cerevisiae, at 92 h and 144 h of fermentation, during its early and late stationary growth phase and at 187 h of fermentation, during its phase of growth decline.
2012-06-12 | E-GEOD-38582 | biostudies-arrayexpress
Project description:Purpose: Zinc deficiency (ZnD) and iron deficiency (FeD), excess Zn (ZnE) and cadmium exposure (CdE) are major environmental problems for crop cultivation. Methods: Applying Tag-Seq technology to leaves of Brassica rapa grown under FeD, ZnD, ZnE or CdE conditions, with normal conditions as a control, we examined global gene expression changes and compared the expression patterns of multiple paralogs. Results: We identified 812, 543, 331 and 447 differentially expressed genes under FeD, ZnD, ZnE and CdE conditions, respectively, in B. rapa leaves.Further analysis revealed that genes associated with Zn, Fe and Cd responses tended to be over-retained in the B. rapa genome. Most of these multiple-copy genes showed the same direction of expression change under stress conditions. Conclusion: We conclude that the duplicated genes involved in trace element responses in B. rapa are functionally redundant, making the regulatory network more complex in B. rapa than in Arabidopsis thaliana. In total, there were 15 Digital gene expression libraries, one for each of the three replicates under the four trace metal element treatments and normal nutrient supply conditions as a control.
2014-09-30 | E-GEOD-55264 | biostudies-arrayexpress
Project description:Parkinson's Disease (PD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 29 PD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of PD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Alzheimer's disease, multiple sclerosis, and breast cancer) confirmed their specificity.
2012-02-27 | E-GEOD-29654 | biostudies-arrayexpress
Project description:This experiment seeks to ascertain the transcriptional changes in the adult mouse hippocampus (CA1 subregion) that occur following viral knockdown of the histone variant H2A.Z. We are especially interested in understanding the role of this histone variant in memory formation and memory maintenance in the adult central nervous system. This experiment includes 3 groups, each with 3 biological replicates. Samples S108, S109, and S110 are from controls infected with an AAV expressing a scrambled shRNA control. Samples A100, A101, A102, A104, A106, and A107 were infected with an AAV expressing an shRNA against H2A.Z. Samples A100, A101, and A102 were naive animals, whereas samples A104, A106, and A107 were trained in contextual fear conditioning.
2014-09-09 | E-GEOD-58797 | biostudies-arrayexpress
Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 50 AD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of AD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Parkinson's disease and breast cancer, respectively) confirmed their specificity.
2011-07-12 | E-GEOD-29676 | biostudies-arrayexpress
Project description:To identify heifers of contrasting fertility, serial rounds of artificial insemination (AI) were conducted in 201 synchronized crossbred beef heifers. The heifers were then fertility classified based on number of pregnancies detected on day 35 in the four AI opportunities. The reproductive tracts of a subset of the classified heifers were obtained on day 14 of the estrous cycle. Microarray analysis revealed differences in the endometrial transcriptome based on fertility classification. Endometrium from 36 fertility-classified heifers (highly fertile, n=14; subfertile, n=12; infertile, n=10) was analyzed for differences in their transcriptome using a bovine microarray.
2013-04-23 | E-GEOD-46274 | biostudies-arrayexpress
Project description:To identify gene expression differences between Oncorhynchus mykiss that migrate and those that reside in freshwater, we compared gill transcriptomes of fish prior to release from a hatchery with those of fish recaptured eight days post-release while all fish were still in freshwater, but some were captured next to the hatchery (non-migrants) and others were captured moving toward the ocean (migrants). The in-hatchery sampling method represents a highly similar environment for all the fish, and allows for the determination of activated genes predictive of smolting programs prior to release into streams. Morphological (e.g. color) and physiological (gill NaCl-ATPase activity) data were also obtained and correlated to gene expression differences to aid in predictions. Gill tissue was sampled for transcriptome profiling 13 days prior to two different releases from the hatchery (total sampled within hatchery n = 19). Samples were also taken eight days after the two releases near-hatchery (total in-creek n = 20) or migrating towards the ocean but still in freshwater (second release only n = 20). Finally, 48 days after the second release a final set of resident fish were sampled near the hatchery (n =10). In terms of time after release, the most parallel comparison is the second 8 day post release sample in-creek and migrating. Although all samples were obtained in freshwater, the samples with the most similar local environment are the pre-release samples.
2014-03-04 | E-GEOD-48844 | biostudies-arrayexpress
Project description:This study is an attempt to characterize the molecular basis for the functional differences between TFAP2A and TFAP2C. Recent findings have highlighted a critical role for the TFAP2C (AP-2M-NM-3) transcription factor in maintaining the luminal phenotype through the regulation of luminal-associated genes. Of particular interest is that the highly homologous AP-2 family member, TFAP2A (AP-2M-NM-1), is expressed in luminal breast cancer but appears to have a functionally distinct role in gene regulation. There is 83% similarity between TFAP2A and TFAP2C with 76% identity in the carboxyl-half of the proteins containing the DNA binding and dimerization domains. Although the two family members appear to have complementary and overlapping roles in regulating neural crest development, they have clear functional differences with regard to regulation of ERM-NM-1 expression. The global genomic binding pattern for TFAP2A and TFAP2C is highly similar. Genomic binding for TFAP2A and TFAP2C in the regulatory region for luminal-associated genes further demonstrated co-localization of the two factors. On the other hand, clear functional differences exist when comparing the effect on the pattern of gene expression following knockdown of TFAP2A vs. TFAP2C. In each case, knockdown of TFAP2C resulted in an abrogation of expression (RNA and protein) of the luminal-associated gene, whereas, knockdown of TFAP2A had minimal or no effect. By contrast, a known TFAP2A target gene, CDKN1A, was responsive to TFAP2A only. 1 ChIP-Seq data for TFAP2A in human breast carcinoma cell line MCF-7. See associated publication.
2014-04-12 | E-GEOD-44257 | biostudies-arrayexpress