Growth rate-corrected (GR) dose-response metric signatures across a panel of 71 breast cancer cell lines treated with a library of small molecule and antibody perturbagens. Dataset 4 of 4: Median, upper quartile, and lower quartile GR metrics per perturbagen class.
Project description:Tumor formation is in part driven by copy number alterations (CNAs), which can be measured using array Comparative Genomic Hybridization (aCGH). Identifying regions of DNA that are gained or lost in a significant fraction of tumor samples can facilitate identification of genes possibly related to the development of cancer. Until now, no method has been described that provides a statistical framework in which these regions can be identified without prior discretization of the aCGH data. Kernel Convolution - a Statistical Method for Aberrant Region deTection (KC-SMART) is a new approach which inputs continuous aCGH data to identify regions that are significantly aberrant across an entire tumor set. KC-SMART uses kernel convolution to generate a Kernel Smoothed Estimate (KSE) of CNAs across the genome, aggregated over all tumors. By varying the width of the kernel function, a scale space is created which enables the detection of aberrations of varying size. In an analysis of 89 human sporadic breast tumors KC-SMART performs better than a previously published method, STAC. Our method not only identified aberrations that are strongly associated with clinical parameters, but also showed stronger enrichment for known cancer genes in the detected regions. Furthermore, KC-SMART identifies 18 aberrant regions in mammary tumors from p53 conditional knock-out mice. These regions, combined with gene expression micro-array data, point to known cancer genes and novel candidate cancer genes. 19 mouse mammary tumors samples were measured against spleen-derived DNA from the same animal on our in-house aCGH platform. Goal of the study was to assess recurrent genomic aberrations in these tumors. This is a tissue specific knockout of p53. Experiments were perfomed in dye-swap
Project description:Comparisons between the sample groups (normal elderly control (NEC) and Alzheimer disease (AD)) allowed the identification of genes with disease expression patterns associated with the glutathione S-transferase M3 single nucleotide polymorphism rs7483. Keywords: biological repeat Peripheral blood mononuclear cells (BMC) were obtained from normal elderly control (NEC) and Alzheimer disease (AD) subjects. Targets from biological replicates of NEC (n=18) and AD (n=16) were generated and the expression profiles were determined using the NIA Human MGC cDNA microarray.
Project description:This SuperSeries is composed of the following non-comparable subset Series which represent two different studies: GSE4226: Alzheimer's Disease peripheral blood mononuclear cell expression GSE4227: Alzheimer's disease and GSTM3 [Val255] single nucleotide polymorphism linkage with peripheral BMC expression Keywords: SuperSeries Refer to individual Series
Project description:In Bacillus cereus the catabolite control protein CcpA was shown to be involved in optimizing the efficiency of glucose catabolism by activating genes encoding glycolytic enzymes including a non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase that mediates conversion of D-glyceraldehyde 3-phosphate to 3-phospho-D-glycerate in one single step, and by repressing genes encoding the citric acid cycle and gluconeogenic enzymes. Two B. cereus-specific CcpA-regulated operons were identified, encoding enzymes involved in the catabolism of fuculose/arabinose and aspartate. In addition, a genome search using the CRE-site consensus predicted the B. cereus CcpA regulon to include 10 PTS-system gene clusters as well as genes coding for overflow metabolic enzymes leading to acetoin and acetate. Notably, catabolite repression of the genes encoding non-hemolytic enterotoxin (Nhe) and hemolytic (Hbl) enterotoxin appeared CcpA-dependent, and for the corresponding enterotoxin operons, putative CRE-sites were identified. This points to metabolic control of enterotoxin gene expression and suggests that CcpA-mediated glucose sensing provides an additional mode of control to PlcR activated expression of nhe and hbl genes in B. cereus. Keywords: Time course analysis by comparing transriptomes of the wildtype and the ccpA deleton strain. The wildtype (B. cereus ATCC 14579) and ccpA deletion strain were sampled during aerobic growth in Brain heart infusion broth. Samples of wildtype and ccpA deletion strain were compared at 4 time points, i.e. early exponential (OD600 0.2), mid-exponential (OD600 0.8), transition phase (OD600 4), and stationary phase (OD600 8). For each time point biological duplo's were obtained, which were subsequently differently labelled to perform a dye swap.
Project description:Investigation of whole genome gene expression level changes in anaerobic, nitrate-dependent Fe(II) oxidation in the chemolithoautotrophic bacterium Thiobacillus denitrificans Here we report on a study to identify genes associated with nitrate-dependent Fe(II) oxidation by whole-genome transcriptional (microarray) assays including the use of FeCO3, Fe2+, and U(IV) oxides as electron donors under denitrifying conditions. A 25 chip study using total RNA recovered from wild-type T. denitrificans was cultivated at 30oC under strictly anaerobic conditions with growth medium that contained 20 mM thiosulfate, 20 mM nitrate, and 30 mM bicarbonate (pH ~7) and exposed to 8 treatments. Each chip measures the expression level of 2832 ORFs with N 24-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
Project description:Comparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype) As these cells demonstrate gain of chromosome 5p during this time, mRNA expression profiling data interrogated for over-expressed genes on 5p that may be important in cervical neoplastic progression. Analyzed global mRNA expresion profiles from W12 Series 1 cells (3 replicates at passage 22 versus 3 replicates at passage 19)
Project description:The molecular mechanisms by which floral homeotic genes act as major developmental switches to specify the identity of floral organs, are still largely unknown. Floral homeotic genes encode transcription factors of the MADS-box family, which are supposed to assemble in a combinatorial fashion into organ-specific multimeric protein complexes. Major mediators of protein interactions are MADS-domain proteins of the SEPALLATA subfamily, which play a crucial role in the development of all types of floral organs. In order to characterize the roles of the SEPALLATA3 transcription factor complexes at the molecular level, we analyzed genome-wide the direct targets of SEPALLATA3. We used chromatin immunoprecipitation followed by ultrahigh-throughput sequencing or hybridization to whole-genome tiling arrays to obtain genome-wide DNA-binding patterns of SEPALLATA3. The results demonstrate that SEPALLATA3 binds to thousands of sites in the genome. Most potential target sites that were strongly bound in wild-type inflorescences, are also bound in the floral homeotic agamous mutant, which displays only the perianth organs, sepals and petals. Characterization of the target genes shows that SEPALLATA3 integrates and modulates different growth-related and hormonal pathways in a combinatorial fashion with other MADS-box proteins and possibly with non-MADS transcription factors. In particular, the results suggest multiple links between SEPALLATA3 and auxin signaling pathways. Our gene expression analyses link the genomic binding site data with the phenotype of plants expressing a dominant repressor version of SEPALLATA3, suggesting that it modulates auxin response to facilitate floral organ outgrowth and morphogenesis. Furthermore, the binding of the SEPALLATA3 protein to cis-regulatory elements of other MADS-box genes and expression analyses reveal that this protein is a key component in the regulatory transcriptional network underlying the formation of floral organs. ChIP experiments were performed on Arabidopsis wildtype and agamous mutant inflorescences using an antibody raised against a C-terminal peptide of SEP3. As control, ChIP experiments were performed on the sep3 mutant.