Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22164046.fastq.gz | Fastqsanger.gz | |||
| SRR22122568.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Acute myeloid leukemia (AML) is a hematologic malignancy for which several epigenetic regulators have been identified as therapeutic targets. Here we report the development of cereblon-dependent degraders of IKZF2 and casein kinase 1 alpha (CK1α) termed DEG-35 and DEG-77. We utilized a structure-guided approach to develop DEG-35 as a nanomolar degrader of IKZF2, a hematopoietic specific transcription factor that contributes to myeloid leukemogenesis. DEG-35 possesses additional substrate specificity for the therapeutically relevant target CK1α which was identified through unbiased proteomics and a PRISM screen assay. Degradation of IKZF2 and CK1α blocks cell growth and induces myeloid differentiation in AML cell lines through CK1α–p53- and IKZF2-dependent pathways. Target degradation by DEG-35 or the analog DEG-77 delays leukemia progression in murine and human AML mice models. Overall, we provide a strategy for multi-targeted degradation of IKZF2/CK1α to enhance efficacy against AML that may be expanded to additional targets and indications.
2023-03-08 | PXD039474 | Pride
Project description:Deg proteases are involved in protein quality control and response to stress in prokaryotic organisms. Out of the 16 Deg-encoding genes of Arabidopsis, the products of three, Deg1, Deg5 and Deg8, are located in the thylakoid lumen. Deg1 forms homo-hexamers, degrading photosynthetic proteins, especially during photoinhibition. Deg5 and Deg8 form hetero-complexes, performing apparently similar functions, raising the question whether the two complexes are redundant. To answer this, single, double and triple knockout mutants were generated and their phenotypes were compared. Under optimal growth conditions deg5 and deg8 mutants looked like WT, whereas all combinations of deg1 mutants were smaller and more sensitive to photoinhibition. Under harsher conditions, deg5 and deg8 mutants were also affected, although less than deg1 mutants. Overexpression of Deg5-Deg8 could partially compensate for the loss of Deg1, but only in optimal conditions. Comparative proteomic analysis of deg1 mutants vs. WT revealed moderate up-regulation of thylakoid proteins involved in photoprotection, assembly, repair and house-keeping functions, and down-regulation of all photosynthetic complexes, consistent with the reduced growth of the deg1 mutants. Testing the steady-state level of Deg proteases in WT plants demonstrated that Deg1 was approximately two-fold more abundant than the Deg5-Deg8 complex. Moreover, recombinant Deg1 had higher in vitro proteolytic activity compared with Deg5 and Deg8. Affinity enrichment assays on transgenic plants expressing epitope-tagged Deg proteases revealed that Deg1 was pulled-down almost exclusively, whereas Deg5 and Deg8 were associated with a plethora of thylakoid membrane and lumen proteins, suggesting that they are capable of binding potential substrates, but are unable to degrade them efficiently. Two of the co-precipitated proteins, TL29 and Psb27-H1, were found slightly up-regulated in the triple mutant, suggesting that they are substrates of lumenal Deg proteases. Other pulled-down proteins were the D1 protein, LHCB proteins and subunits of the OEC of PSII, and components of the Cyt b6-f and NADH dehydrogenase complexes, suggesting that these might also be substrates of lumenal Deg proteases. Altogether, the results of this study suggest that differences in abundance and proteolytic activity are the source of the differential importance of the two Deg protease complexes observed in vivo.
2022-01-17 | PXD008920 | Pride
Project description:The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes:
1. DEG analysis and GSEA analysis comparing IBN-R and IBN-S cells
2. DEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment.
| EGAS00001006832 | EGA
Project description:Heatshock (30 to 37 deg C) and Coldshock (37 to 30 deg C) experiment looking at 5, 15, 30, 45 and 60 mins after the temp change in each condition.
2014-05-14 | E-MTAB-2219 | biostudies-arrayexpress
Project description:Transcriptional profiling of C. albicans in biofilms after 90 min of adherence or 8 h, 24 h, or 48 h of development; compared to C. albicans in suspension cultures grown to log at 30 deg or 37 deg or grown to stationary phase at 30 deg or collected from the unadhered cells in the biofilm assay. At least 2 biological replicates for each condition. All experiments are multiple condition: C. albicans in particular growth condition vs. mixed reference of all conditions in that experiment.
2014-10-01 | E-GEOD-61143 | biostudies-arrayexpress
Project description:We measured global mRNA expression in peripheral blood mononuclear cells (PBMC) from 45 individuals, comprising of 23 RRMS patients and 22 healthy controls. A gender-based case-control analysis was performed to derive the differentially expressed genes (DEG) in women and men. In contrast to the distinct blood gene signatures, several biological processes(gene ontology) related to transcriptional regulation was shared among the two gender-based DEG. Further, the systems biology analysis revealed that the several interactors were common to the female and male DEG, predominantly ones that participating in epigenetic regulation of gene expression.
2012-03-31 | E-MTAB-380 | biostudies-arrayexpress
Project description:To date, a universal biomarker panel with a potential to predict high-risk pregnancies or adverse pregnancy outcome does not exist. Transcriptomic approach, a measure of gene expression levels across the genome, is a powerful tool to capture differentially expressed genes (DEG) in various conditions, including human trisomy of chromosome 21 (Ts21). DEG can be used to design a biomarker set as a diagnostic-predictive tool for various conditions of heterogeneous aetiology in a prenatal setting. In the search of novel biomarker set to predict high-risk pregnancies, we performed global expression profiling to find DEG in Ts21 used as a model. Subsequently we performed targeted validation and diagnostic performance evaluation on a larger group of case and control samples. Initially, transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using Agilent 4x44K expression microarrays. DEG were discovered using linear regression modelling implemented in limma package. Datasets from Ts21 transcriptomic studies available at GEO repository were incorporated to select our preliminary top DEG. Subsequently, selected top DEG were validated using RT-PCR quantification on independent sample of 16 cases with Ts21 and 32 controls, as well as new datasets from previously performed expression studies in Ts21. The classification was performed using support vector machine classification kernel and evaluated using leave-one-out cross validation approach. Transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using Agilent 4x44K expression microarrays.
2013-06-19 | E-GEOD-48051 | biostudies-arrayexpress
Project description:Lenalidomide achieves its therapeutic efficacy by recruiting and removing proteins of therapeutic interest through the E3 ligase substrate adapter cereblon. Here, we report the rational design and characterization of 81 cereblon ligands for their ability to degrade the transcription factor Helios (IKZF2) and casein kinase 1 alpha (CK1α) in acute myeloid leukemia MOLM-13 cells. Using a structure-based approach, we identified a key naphthamide scaffold that depleted both intended targets. Structure-activity relationship studies for degradation of the desired targets over other targets (IKZF1, GSPT1) afforded an initial lead compound, termed DEG-35. A subsequent scaffold replacement campaign informed by degradation profiles against a panel of substrates identified DEG-77, which selectively degrades IKZF2 and CK1α, and possesses suitable pharmacokinetic properties, solubility, and selectivity for in vivo studies. Finally, we show that DEG-77 has antiproliferative activity in diffuse large B cell lymphoma (DLBCL) cell line OCI-LY3 and ovarian cancer cell line A2780, indicating that these dual degraders and their targets may have efficacy against additional cancer types.
2024-01-04 | PXD045327 | Pride
Project description:Transcriptional profiling of C. albicans in biofilms after 90 min of adherence or 8 h, 24 h, or 48 h of development; compared to C. albicans in suspension cultures grown to log at 30 deg or 37 deg or grown to stationary phase at 30 deg or collected from the unadhered cells in the biofilm assay.
2014-10-01 | GSE61143 | GEO