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GSE144826
Homo sapiens
878 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
Publication Title
Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Statins and bisphosponates (BPs) are two distinct classes of isoprenoid pathway inhibitors targeting HMG-CoA reductase (upstream enzyme) and Farnesyl-pyrophospate synthase (downstream enzyme) respectively. Here we conducted a comparative study of two representatives of these classes, fluvastatin (Fluva) and Zoledronate (Zol), to assess the differences in their in vivo metastatic potentials and pharmacogenomic profiles. Both drugs, being administered after emergence of detectable metastases, appeared to be potent metastasis inhibitors in MDA-MB-231 breast cancer metastasis model. We observed a reduced number of metastatic sites under Fluva, but not Zol treatment. Combinatorial in vivo treatment by Fluva and Zol showed no synergy for these drugs, as reported earlier on the basis of in vitro studies (Budman DR, Oncology 2006), staying in line with similarity of their transcriptomic profiles. Comparison of Zol and Fluva transcriptomic profiles revealed similar patterns of affected genes (describe involved genes functions) through different kinetics (when treated with IC50 determined for 72h treatment, the majority of changes were observed after 24h incubation with Fluva , and only after 48h incubation with Zol at 72h-IC50 or after 24h treatment with its 3 times higher dose). We demonstrated here that targeting different enzymes of the same pathway neither necessarily leads to distinct changes in gene profiles, nor to synergy for in vivo anti-metastatic potential.
Publication Title
Transcriptome analysis and in vivo activity of fluvastatin versus zoledronic acid in a murine breast cancer metastasis model.
Sample Metadata Fields
Cell line, Time
View Samples- Oryza sativa
- 16 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Leaf samples were used. We exposed young seedlings to NaCl and drought.
Publication Title
Identification of cis-regulatory elements associated with salinity and drought stress tolerance in rice from co-expressed gene interaction networks.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Two-dimensional (2D) nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by monitoring change in transcriptome profile uncovers key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes is observed due to nanosilicate exposure as more than 4,000 genes are differentially expressed. The change in mRNA expression levels reveal clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to cell membrane and subsequent cellular internalization activate stress-responsive pathways such as mitogen activated protein kinase (MAPK), which subsequently directs hMSC differentiation towards osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial-cell interactions, illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment. Overall design: Examination of affect of 2D nanosilicates on hMSCs
Publication Title
Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Oryza sativa
- 78 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice (Oryza sativa, ssp. Japonica, cv. Nipponbare 1) plants were grown in a Conviron PGR 15 growth chamber using precise control of temperature, light, and humidity.<br></br>Diurnal (driven) conditions included 12L:12D light cycles and 31C/20C thermocycles in three different combinations. These were: photocycles (LDHH), 12 hrs. light (L)/12 hrs. dark (D) at a constant temperature (31C; HH); photo/thermocycles (LDHC): 12 hrs. light (L) /12 hrs. dark (D) with a high day temperature (31C) and a low night temperature (20C); and thermocycles (LLHC): continuous light (LL) with 12 hrs. high/12 hrs. low temperature (31C, day; 20C, night). Light intensity and relative humidity were 1000 micromol m-2s-2 and 60%, respectively.<br></br>Three-month-old rice plants were entrained for at least one week under the respective condition prior to initiation of each experiment. Leaves and stems from individual rice plants were collected every four hours for 48 hrs in driven (diurnal) conditions followed by a two day freerun spacer under continuous light/temperature followed by two additional days of sampling under the same continuous free run condition.<br></br>
Publication Title
Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Oryza sativa
- 37 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice (Oryza sativa, spp. Indica, cv. 93-11) plants were grown in a Conviron PGR 15 growth chamber using precise control of temperature, light, and humidity.<br></br>Diurnal (driven) conditions included 12L:12D light cycles and 31C/20C thermocycles in three different combinations. These were: photocycles (LDHH), 12 hrs. light (L)/12 hrs. dark (D) at a constant temperature (31C; HH); photo/thermocycles (LDHC): 12 hrs. light (L) /12 hrs. dark (D) with a high day temperature (31C) and a low night temperature (20C); and thermocycles (LLHC): continuous light (LL) with 12 hrs. high/12 hrs. low temperature (31C, day; 20C, night). Light intensity and relative humidity were 1000 micromol m-2s-2 and 60%, respectively.<br></br>Three-month-old rice plants were entrained for at least one week under the respective condition prior to initiation of each experiment. Leaves and stems from individual rice plants were collected every four hours for 48 hrs in driven (diurnal) conditions followed by a two day freerun spacer under continuous light/temperature followed by two additional days of sampling under the same continuous free run condition.
Publication Title
Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We investigated the impact of on miR-H1 and miR-K12-3-3p- on host transcriptome focusing on gingival epithelial cells that are target sites for various HHV.
Publication Title
Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Heme Oxygenase-1 (HO-1) is expressed in many cancers and influences the growth, survivall and metastasis of tumors, however, the molecular mechanisms remains largely unknown. To identify a common mechanism of action of HO-1 in cancer, we studied the global effect of HO-1 on the transcriptome of multiple tumors. Genome-wide expression profiling of HO-1 expressing versus HO-1 silenced cancer cells and a further data mining analysis of the preexisting expression database of 190 human tumors of 14 cancer types led us to identify 14 genes, the expression of which correlated firmly and universally with that of HO-1 (P < 0.001). These genes included regulators of cell plasticity and extracellular matrix remodeling (MMP2, ADAM8, TGF1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30) and phosphorylation (ALPPL2). PXDN, one of the genes being co-expressed with HO-1, was selected for further analysis. Immunofluorescence and western blotting confirmed positive correlation of PXDN with HO-1 levels in BeWo cancer cells as well as co-localization in invasive extravillous trophoblast cells of first trimester placenta. Loss of HO-1 in BeWo cells correlated with reduced cell adhesion to Collagen type I, Fibronectin and Laminin. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo cells led to reduced cell attachment to Laminin and Fibronectin coated wells.
Publication Title
Transcriptome analysis of human cancer reveals a functional role of heme oxygenase-1 in tumor cell adhesion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
Publication Title
Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants were exposed to NaCl (150mM) stress for 24 hours
Publication Title
Heterologous Expression of Serine Hydroxymethyltransferase-3 From Rice Confers Tolerance to Salinity Stress in <i>E. coli</i> and Arabidopsis.
Sample Metadata Fields
Age
View Samples