This SuperSeries is composed of the SubSeries listed below.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Specimen part, Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Cell line
View SamplesA genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Specimen part
View SamplesExpression data were generated on 136 subjects from the COPDGene study using Affymetrix microarrays. Multiple linear regression with adjustment for covariates (gender, age, body mass index, family history, smoking status, pack years) was used to identify candidate genes and Ingenuity Pathway Analysis was used to identify candidate pathways.
Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease.
Sex, Specimen part
View SamplesA375P melanoma cells were treated with 1uM of the MEK inhibitor PD184352 or 0.4uM of the V600EBRAF inhibitor PLX4720 for 2hr, 6hr and 24hrs.
Identification of direct transcriptional targets of (V600E)BRAF/MEK signalling in melanoma.
Cell line, Treatment, Time
View SamplesThe development of high-throughput genomic technologies has revealed that a large fraction of the genomes of eukaryotes is associated with the expression of noncoding RNAs. One class of noncoding RNA, the cis-natural antisense transcripts (cis-NATs), are particularly interesting as they are at least partially complementary to the protein-coding mRNAs. Although most studies described cis-NATs involved in the regulation of transcription, a few reports have shown recently that cis-NATs can also regulate translation of the cognate sense coding genes in plants and mammals. In order to identify novel examples of translation regulator cis-NATs in Arabidopsis thaliana, we designed a high-throughput experiment based on polysome profiling and RNA-sequencing. Expression of cis-NATs and translation efficiency of the cognate coding mRNAs were measured in roots and shoots in response to various conditions, including phosphate deficiency and treatment with phytohormones. We identified several promising candidates, and validated a few of them experimentally, in Arabidopsis thaliana transgenic lines over-expressing in trans the translation regulator candidate cis-NATs. Overall design: total RNA and polysomal RNA was sequenced from Arabidopsis thaliana whole seedlings grown in high or low pohsphate content, or from roots or shoots from seedlings treated or not with different phytohormones (Ctrl, IAA, ABA,MeJA and ACC). 3 biological replicates were analyzed for each of the 12 experimental conditions.
Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions.
Specimen part, Treatment, Subject
View SamplesWe used Affymetrix microarray analyses of thirty-two individual Vitis vinifera cv. Cabernet Sauvignon berries sampled from two clusters at fifty-percent ripening initiation. By delineating four developmental stages of ripening initiation, we demonstrate that color is a statistically significant indicator of transcriptional state during ripening initiation. We report on clustered gene expression patterns which were mined for genes annotated with signal transduction functions in order to advance regulatory network modeling of ripening initiation in grape berries.
Gene expression analyses in individual grape (Vitis vinifera L.) berries during ripening initiation reveal that pigmentation intensity is a valid indicator of developmental staging within the cluster.
No sample metadata fields
View SamplesUstilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses.
Two linked genes encoding a secreted effector and a membrane protein are essential for Ustilago maydis-induced tumour formation.
Specimen part, Disease, Disease stage
View SamplesShort-term bed rest is used to simulate muscle disuse in humans. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). Overall design: RNA was isolated and sequenced from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9) and OLD (N=18) men and women before and after five days of bed rest. Sequencing libraries (18 pM) were chemically denatured and applied to an Illumina TruSeq v3 single read flowcell using an Illumina cBot. Hybridized molecules were clonally amplified and annealed to sequencing primers with reagents from an Illumina TruSeq SR Cluster Kit v3-cBot-HS (GD-401-3001). Following transfer of the flowcell to an Illumina HiSeq 2500 instrument (HCS v2.0.12 and RTA v1.17.21.3), a 50 cycle single read sequence run was performed using TruSeq SBS v3 sequencing reagents (FC-401-3002). The design formula was constructed by following the section on group-specific condition effects, individuals nested within groups in the DESeq2 vignette. The design included age + age:nested + age:time to test for differences in bed rest in old subjects, young subjects and the interaction, in this case if bed rest effects are different between the two age groups (where age is young or old, nested is patient number nested by age and time is pre- or post-bed rest). A similar design was used to determine susceptibility to disuse-induced insulin resistance, where “susceptibility” took the place of “age”.
Disuse-induced insulin resistance susceptibility coincides with a dysregulated skeletal muscle metabolic transcriptome.
Sex, Specimen part, Subject, Time
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