Time-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control), as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model.
Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays.
No sample metadata fields
View SamplesThermal injury incites inflammatory responses that often transcend the local environment and lead to structural deficiencies in skin that give way to scar formation. We hypothesized that extensive perturbations within burned skin following thermal insult and during subsequent events of wound repair induce vast alterations in gene expression that likely serve as a wound and systemic healing deterrent. A high-throughput microarray experiment was designed to analyze genetic expression patterns and identify potential genes to target for therapeutic augmentation or silencing. The study compares gene expression from burn wound margins at various times following thermal injury to expression observed in normal skin. Utilizing this design, we report that the totality of gene expression alterations is indeed enormous. Further, we observed that the differential expression of many inflammatory and immune response genes appear to be continually up-regulated in burn wound margins seven days or more after initial thermal insult. As it is well established that the inflammatory process must abate for wound healing to proceed, the finding of ongoing local inflammation is cause for further investigation. To our knowledge, this is the first report of the gene expression alterations induced by thermal injury of human skin. As such, it provides a wealth of data to mine with the ultimate goal of better understanding the local pathophysiologic changes at the site of thermal injury that not only affect wound healing capacity, but may also contribute to systemic derangements within the burn patient.
A microarray analysis of temporal gene expression profiles in thermally injured human skin.
Sex
View SamplesIn the mammalian central nervous system (CNS) an important contingent of dopaminergic neurons are localized in the substantia nigra and in the ventral tegmental area of the ventral midbrain. They constitute an anatomically and functionally heterogeneous group of cells involved in a variety of regulatory mechanisms, from locomotion to emotional/motivational behavior. Midbrain dopaminergic neuron (mDA) primary cultures represent a useful tool to study molecular mechanisms involved in their development and maintenance. Considerable information has been gathered on the mDA neurons development and maturation in vivo, as well as on the molecular features of mDA primary cultures. Here we investigated in detail the gene expression differences between the tissue of origin and ventral midbrain primary cultures enriched in mDA neurons, using microarray technique. We integrated the results based on different re-annotations of the microarray probes. By using knowledge-based gene network techniques and promoter sequence analysis, we also uncovered mechanisms that might regulate the expression of CNS genes involved in the definition of the identity of specific cell types in the ventral midbrain. We integrate bioinformatics and functional genomics, together with developmental neurobiology. Moreover, we propose guidelines for the computational analysis of microarray gene expression data. Our findings help to clarify some molecular aspects of the development and differentiation of DA neurons within the midbrain.
Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures.
Specimen part, Disease
View SamplesComparison of BOLITA mutant leaves (gain-of-function mutant) vs. wild type leaves, grown in the same conditions. The BOLITA (BOL) gene (At1g24590), an AP2/ERF transcription factor, was characterized with the help of an activation tag mutant and overexpression lines in Arabidopsis and tobacco. The leaf size of plants overexpressing BOL was smaller than wild type plants due to a reduction in both cell size and cell number. Moreover, severe overexpressors showed ectopic callus formation in roots. Accordingly, global gene expression analysis using the overexpression mutant reflected the alterations in cell proliferation, differentiation and growth through expression changes in RBR, CYCD, and TCP genes, as well as genes involved in cell expansion (i.e. expansins and the actin remodeling factor ADF5). Furthermore, the expression of hormone signaling (i.e. auxin and cytokinin), biosynthesis (i.e. ethylene and jasmonic acid) and regulatory genes was found to be perturbed in bol-D mutant leaves. The gene is expressed at the shoot apical meristem, and more intensely at leaf primordia. It is also expressed at very young leaves, and flower buds. The gene is closely related to DORNROSCHEN.
BOLITA, an Arabidopsis AP2/ERF-like transcription factor that affects cell expansion and proliferation/differentiation pathways.
Age, Specimen part
View SamplesMicroarray was used to study global gene expression of a cell culture model based on SV40-immortalized human corneal epithelial (iHCE) cells. The gene expression profile of the cell line was compared to the normal human corneal epithelium. Affymetrix HG-U133A GeneChips were used for microarray experiments and results were validated by performing RT-qPCR for selected genes. iHCE was found to over- and under-express 22 % and 14 % of the annotated genes, respectively. The results of this study suggest that differences between iHCE cells and normal corneal epithelium are substantial and therefore the use of these cells in corneal research should be considered with caution.
Gene expression analysis in SV-40 immortalized human corneal epithelial cells cultured with an air-liquid interface.
Cell line
View Samples183 breast tumors from the Helsinki Univerisity Central Hospital with survival information
Variants on the promoter region of PTEN affect breast cancer progression and patient survival.
No sample metadata fields
View SamplesTo identify novel Nurr1 target genes we have used microarrays strategies in rat midbrain primary cultures, enriched in dopaminergic neurons, by the action of basic fibroblast growth factor (bFGF, 20ng/ml) and Sonic hedgedog (SHH), following upregulation of Nurr1 expression by depolarization.To this aim we have treated the cultures after 9 days in vitro for 2h with high KCl and collected 30 min or 2 h after the end of depolarization (2h + 30 min or 2h + 2h). With this experimental protocol we have identify a putative Nurr1 regulator and Nurr1 target
Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro.
Specimen part
View SamplesHair Follicle regeneration relies on both epithelial components (bulge and hair germ cells) and a mesenchymal one (dermal papilla cells).
A two-step mechanism for stem cell activation during hair regeneration.
Specimen part
View SamplesEpigenetic changes play a role in the pathogenesis of myeloid malignancies and hypomethylating agents have shown efficacy in these diseases. We studied the apoptotic effect, the genome-wide methylation and gene expression profiles in HL60 cells following decitabine treatment, using micro-array technologies. Decitabine treatment resulted in a decrease in global DNA methylation, corresponding to 4876 probeset IDs with significantly reduced methylation levels, while expression of 2583 IDs was induced. The integrated analysis identified 160 genes demethylated and upregulated by decitabine, mainly including development and differentiation pathways genes. Genes target of polycomb group protein regulation were overrepresented in this group. Apoptosis was induced by decitabine and apoptosis-specific PCR arrays more precisely indicated decitabine-induced upregulation of 13 apoptosis-related genes, in particular Dap-kinase 1 and Bcl2L10. Correspondingly, in primary patient samples, BCL2L10 was hypermethylated in 45% of AML, 43% of therapy-related myeloid neoplasms, 12% of MDS and in none of the controls.
Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia.
Specimen part
View SamplesMyotonic Dystrophy Type-2 (DM2) is an autosomal dominant disease caused by the expansion of a CCTG tetraplet repeat. It is a multisystemic disorder, affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system.
Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2.
Sex, Age, Specimen part, Disease, Disease stage
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