EGAS00001001604-sc-20180614 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001004162 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:<p>Recently developed methods that utilize partitioning of long genomic DNA fragments, and barcoding of shorter fragments derived from them, have succeeded in retaining long-range information in short sequencing reads. These so-called read cloud approaches represent a powerful, accurate, and cost-effective alternative to single-molecule long-read sequencing. We developed software, GROC-SVs, that takes advantage of read clouds for structural variant detection and assembly. We apply the method to two 10x Genomics data sets, one chromothriptic sarcoma with several spatially separated samples, and one breast cancer cell line, all Illumina-sequenced to high coverage. Comparison to short-fragment data from the same samples, and validation by mate-pair data from a subset of the sarcoma samples, demonstrate substantial improvement in specificity of breakpoint detection compared to short-fragment sequencing, at comparable sensitivity, and vice versa. The embedded long-range information also facilitates sequence assembly of a large fraction of the breakpoints; importantly, consecutive breakpoints that are closer than the average length of the input DNA molecules can be assembled together and their order and arrangement reconstructed, with some events exhibiting remarkable complexity. These features facilitated an analysis of the structural evolution of the sarcoma. In the chromothripsis, rearrangements occurred before copy number amplifications, and using the phylogenetic tree built from point mutation data, we show that single nucleotide variants and structural variants are not correlated. We predict significant future advances in structural variant science using 10x data analyzed with GROC-SVs and other read cloud-specific methods.</p>
| phs001255 | dbGaP
Project description:<p>While the incidence of esophageal adenocarcinoma (EAC) has risen drastically in Western countries over the last 40 years, a similar trend has not been observed for EAC in China. Here we analyzed mutational spectrum, copy number alterations, and structural variants from whole-genome sequencing of ten Chinese EAC tumor samples and their matched normals, and compared them to EAC tumor specimens from Western countries previously reported. The mutational burden in Chinese EAC was significantly lower than that found in EAC from Western countries. The hallmark A>C mutational signature observed at high frequency in EAC from Western countries, which linked to acid reflux, is completely absent in Chinese samples. Furthermore, none of Chinese samples showed evidence of chromothripsis and genome doubling that often found in EAC from Western countries. In summary, Chinese EAC tumor samples revealed distinct genomic profiles and signatures, suggesting that Chinese EAC may arise from a different etiological pathway.</p>
| phs001696 | dbGaP
Project description:Morphogenesis of vertebrate embryos requires extracellular matrix (ECM) in multiple developmental contexts1. Symmetry-breaking events in initially homogenous tissues trigger collective cellular dynamics which follow fluid-like behaviors, and the ECM, which is in constant engagement with morphing tissues, also undergoes fluid-like motion2–4. Cell and ECM deformations require coordination, however the interplay between them at cellular and tissue-scale remains largely unexplored. Here, we reveal a novel mechanism coupling morphogenetic events and epithelia-driven ECM flow. We show that exposure to ECM components triggers periodic morphogenesis of dome-shaped structures in human pluripotent stem cell monolayers, driven by directional ECM flow towards the sites of morphogenesis. We show that this flow is initiated by local symmetry-breaking events, is driven by microvilli and requires unperturbed flow conditions and cytoskeletal contractility. A theoretical model shows that a reaction-diffusion-like mechanism is responsible for organizing local morphogenesis into global tissue-wide events. The cell patterning landscape predicted by the model is experimentally recapitulated during mesoderm differentiation. We further validate ECM flow in 3D gastruloids and in quail embryos during primitive streak formation. These results uncover a new role for the ECM: in addition to being a site of cell adhesion, structural support and mechanical force generation5, as is currently established, we show that directional transport of ECM, termed ECM flow, is a major contributor in sustaining epithelial morphogenesis and differentiation.
2025-12-17 | GSE284815 | GEO
Project description:In this study we show that lysyl oxidase (LOX), an enzyme involved in maintaining structural integrity of the extracellular matrix, is expressed at low levels in Ewing sarcoma cells and primary tumors and is downregulated by the EWS/FLI1 oncoprotein characteristic of these tumors. Using a doxycycline inducible system to restore LOX expression in an Ewing sarcoma derived cell line, we show that LOX displays tumor suppressor activities. Interestingly, we show that the tumor suppressor activity resides in the propeptide domain of LOX (LOX-PP), an N-terminal domain produced by proteolytic cleavage during the physiological processing of LOX. Finally, we show that LOX-PP inhibits ERK/MAPK signalling pathway, and that many pathways involved in cell cycle progression were significant deregulated by LOX-PP, providing a mechanistic explanation to the cell proliferation inhibition observed upon LOX-PP expression. In summary, our observations indicate that deregulation of the LOX gene participates in Ewing sarcoma development and identify LOX-PP as a new therapeutic target for one of the most aggressive paediatric malignancies. These findings suggest that therapeutic strategies based in the administration of LOX propeptide or functional analogues could be useful in the treatment of this devastating paediatric cancer. A673 cells derived from Ewing sarcoma were genetically enginereed to express LOX-PP upon doxycycline stimulation (72 hours). Three independent experiments from control cells and three independent experiments from A673 cells expressing LOX-PP were done. Gene expression profile in A673 cells expressing LOX-PP vs control cells were compared.
2013-12-31 | E-GEOD-46407 | biostudies-arrayexpress
Project description:The human mitochondrial genome encodes thirteen subunits of the oxidative phosphorylation system essential for energy metabolism to drive cellular activities. Translation of eleven mRNAs by membrane-bound ribosomes is coupled to insertion of the nascent polypeptides into the inner membrane aided by the OXA1L insertase. To this end, the mechanism of membrane insertion of nascent polypeptides and the functional link to the translation process are not understood. Here we applied ribosome profiling to assess translation dynamics in combination with cryo-EM analyses of a COX1 ribosome nascent chain complex to visualize co-translational folding of the nascent chain. We find that the membrane topology of the translation product impacts translation speed and that positioning of amphipathic helices in the ribosome vestibule induces structural changes, correlating with translation stalling events. Thus, our findings reveal a tight link between translation process and folding and membrane insertion of nascent polypeptides at the inner mitochondrial membrane.
2026-03-27 | GSE303205 | GEO
Project description:Genome/chromosome organization is highly ordered and controls nuclear events. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosome organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. Genome-wide distributions of condensin and Pol III factors in fission yeast.
2015-08-12 | E-GEOD-60273 | biostudies-arrayexpress
Project description:Although closely related to plant evolution, polyploid sRNAs (small RNAs) were seldom studied with experiments, especially on genome-wide range. In this study, a rice twin-seeding (two seedlings from the same grain) line SARII-658 was employed to isolate autotriploids. Those autotriploids possess unique merits to study the two interesting topics: (i) natural polyploids; (ii) the autonomy of epigenetic variations (i.e. sRNAs) from genome doubling per se. sRNA libraries were prepared from those diploid-autotriploid twin-seedlings and then were sequenced to produce 13,308,226 short sequence reads in total. Out of the 35,429 miRNA genes and siRNA clusters, 1,547 (4.36%) changed their expression levels for two folds or above after genome doubling (thereinafter, referred those sRNAs as ploidy-sensitive). The expression-unregulated sRNAs (3.71%) were far more than the downregulated ones (0.64%), suggesting that the negative regulation of the coding gene by sRNA increase is more prevalent than the positive regulation during genome doubling. The expression of sRNAs were obviously increased and biased to accumulate toward centromeric and heterochromatic regions, suggesting that sRNAs should play a role in repressing transposition activity during genome doubling. Except transposition activity, the targets of those ploidy-sensitive sRNAs involved many kinds of gene function categories, suggesting an overall regulation of sRNAs to polyploid biological processes. Findings from this study will provide theoretical bases for elucidating epigenetic mechanism of plant and sRNA evolution via genome doubling.
2009-07-15 | GSE14462 | GEO
Project description:In this work, we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n=36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins in all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases (independent of histological subtype) that have a distinct expression profile in a panel of 133 proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.
2021-05-11 | PXD019719 | Pride
Project description:Perturbation of the gated-synchrony system in yeast with phenelzine, an antidepressant drug used in the treatment of affective disorders in humans, leads to a rapid lengthening in the period of the genome-wide transcriptional oscillation. The effect is a concerted, genome-scale change in expression that is first seen in genes maximally expressed in the late-reductive phase of the cycle, doubling the length of the reductive phase within two cycles after treatment. Clustering of genes based on their temporal patterns of expression yielded just three super clusters whose trajectories through time could then be mapped into a simple 3D figure. In contrast to transcripts in the late-reductive phase, most transcripts do not show transients in expression relative to others in their temporal cluster but change their period in a concerted fashion. Mapping the trajectories of the transcripts into low-dimensional surfaces that can be represented by simple systems of differential equations provides a readily testable model of the dynamic architecture of phenotype. In this system, period doubling may be a preferred pathway for phenotypic change. As a practical matter, low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized attribute of phenotype, could be a source of seemingly intractable biological noise in microarray studies. Experiment Overall Design: Phenelzine was added to the system after the first cycle to induce period doubling
2008-06-16 | E-GEOD-9302 | biostudies-arrayexpress