This dataset was used to benchmark the Virtual Inference of Protein-activity by Regulon Readout algorithm (VIPER). Despite recent advances in molecular profiling, proteome-wide assessment of protein activity in individual samples remains a highly elusive target. In stark contrast, protein activity quantitation is increasingly critical to the dissection of key regulatory processes and to the elucidation of biologically relevant mechanisms. Importantly, its value extends to the study of drug activity, as most small molecules inhibit activity of their cognate protein substrates without affecting the proteins or associated mRNAs abundance.
Functional characterization of somatic mutations in cancer using network-based inference of protein activity.
Specimen part, Cell line
View SamplesThe effect of the overexpression of a stabilized version of the transcription factor RELATED TO APETALA2.12 (RAP2.12) on the transcriptome of Arabidopsis rosettes was investigated. To this purpose, 4-week old rosette of wild-type and 35S:13RAP2.12 plants were compared. Samples were composed of pools of 3 plants.
Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.
Age, Specimen part
View SamplesUnderstanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs), and further down to sub-TAD loop domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here we present a novel parameter-free algorithm (CaTCH) that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation which is a simple and biologically relevant property. By applying CaTCH to published Hi-C datasets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal enrichment of CTCF at boundaries, and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that TADs also maximize the likelihood that genes in a domain are co-regulated during differentiation. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the scale of TADs. Our analysis thus suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the genomic position of regulatory sequences. Overall design: The hybrid mouse ESC line F1-21.6 (129Sv-Cast/EiJ), previously described in (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), and 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared by Trizol extraction from the mouse ESC line, and for one NPC clone derived from it. Two biological replicates were collected for ESCs and NPCs. After ribosomal RNA depletion with Ribo-Zero (Illumina), RNA-seq libraries were prepared using ScriptSeq v2 kit (Illumina) following the manufacturer’s instructions. Libraries were prepared in two technical replicates per biological replicate. 50 bp single-end sequencing was performed on Illumina HiSeq 2000 instruments according to manufacturer’s instructions.
Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.
Specimen part, Subject
View SamplesmiRNAs are known to be involved in PDAC tumorigenesis, but only a few biologically relevant gene targets have been identified.
MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.
Specimen part, Subject
View SamplesAnalysis of iPS cells generated with a small molecule, RepSox (RS), as well as a time-course of gene expression changes in cells treated with RS.
A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog.
Specimen part, Cell line
View SamplesThe feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs.
Gene expression profiling of sequential metastatic biopsies for biomarker discovery in breast cancer.
No sample metadata fields
View SamplesIn this study we analyzed the effect of overexpression of an HA-tagged version of the ERF RAP2.12 on the transcriptome levels in aerobic and hypoxic-treated (O2 21% and 1%, respectively) Arabidopsis thaliana rosettes.
Oxygen sensing in plants is mediated by an N-end rule pathway for protein destabilization.
Treatment
View SamplesExpressing a mutant fragment of huntingtin (Htt) in yeast produces several HD-relevant phenotypes. We used microarrays to study global change in expression induced by this mutant htt fragment.
Functional gene expression profiling in yeast implicates translational dysfunction in mutant huntingtin toxicity.
No sample metadata fields
View SamplesOur findings demonstrate beneficial effects of enhancing transactivation function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may provide new targets for therapeutic intervention. Overall design: We mutated conserved lysines in the polyQ AR that are targeted by SUMO, a modification that inhibits AR transactivation function.
Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing.
No sample metadata fields
View Samples