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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Ronan ChalignM-CM-)

PROVIDER: E-GEOD-62907 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Analysis of allele specific expression and its chromatin state to identify genes that are escaping X chromosome inactivation

Project description:Disappearance of the Barr body has long been considered a hallmark of cancer, although whether this corresponds to epigenetic instability and transcriptional reactivation, or to genetic loss, has remained unclear. Here we show that in breast cancer cell lines as well as primary breast tumors, the inactive X chromosome frequently displays a highly abnormal 3D nuclear organization, with global perturbations in its characteristic heterochromatic state, including apparent gain of euchromatic marks and lessening of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells accompanied by a significant degree of X-linked gene reactivation, affecting genes previously implicated in cancer, including the histone deacetylase, HDAC8 and transducin (Beta)-Like 1X-Linked, TBL1X. We provide proof of principle that epigenetic deregulation can indeed perturb the dosage of some X-linked factors and demonstrate that many of these genes are reactivated in primary breast tumors. Our study establishes that the inactive X is subject to epigenetic erosion in a cancer context and sets the stage for the use of chromatin marks and X- chromosome genes as potential biomarkers to assess epigenetic changes in cancer. Examination of allele specific expression of genes in chrX using histone marks, transcriptome, exome and SNP data on two normal cell-line and three cancer cell-line.

2015-01-22 | E-GEOD-62966 | biostudies-arrayexpress

Identification of SNPs using genomic DNA and allele specific expression using nascent RNA on snp6 array

Project description:Disappearance of the Barr body has long been considered a hallmark of cancer, although whether this corresponds to epigenetic instability and transcriptional reactivation, or to genetic loss, has remained unclear. Here we show that in breast cancer cell lines as well as primary breast tumors, the inactive X chromosome frequently displays a highly abnormal 3D nuclear organization, with global perturbations in its characteristic heterochromatic state, including apparent gain of euchromatic marks and lessening of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells accompanied by a significant degree of X-linked gene reactivation, affecting genes previously implicated in cancer, including the histone deacetylase, HDAC8 and transducin (Beta)-Like 1X-Linked, TBL1X. We provide proof of principle that epigenetic deregulation can indeed perturb the dosage of some X-linked factors and demonstrate that many of these genes are reactivated in primary breast tumors. Our study establishes that the inactive X is subject to epigenetic erosion in a cancer context and sets the stage for the use of chromatin marks and X- chromosome genes as potential biomarkers to assess epigenetic changes in cancer. Examination of allele specific expression of genes using nascent RNA on snp6 array by comparing it with snp6 results from genomic DNA.

2015-01-22 | E-GEOD-62965 | biostudies-arrayexpress

Whole exome sequencing and transcription profiling of a patient cohort of oral cavity squamous cell carcinomas

Project description:Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer through the developed and developing world. However, the etiology of OCSCC is still unclear. To explore whether smoking, HPV and/or other underlying genetic and transcriptomic changes could be responsible for the oncogenesis events for OCSCC. A prospective observational study of fresh tissue biopsy from 45 participants with OCSCC collected from Brisbane Head and Neck Clinics between 2013 to 2015. Exploration of the genetic and transcriptomic landscape was performed using RNA sequencing and whole exome sequencing. Identification of HPV was to be performed using DNA PCR genotyping and RNA sequencing. Patient medical records were retrieved and the patient demographics were used to correlate with genomic and transcriptomics analyses, including the location of the tumor within the oral cavity, smoking and alcohol histories.

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Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma

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The genomic landscape of pediatric T-cell acute lymphoblastic leukemia reveals novel X-linked somatic mutations associated with apoptosis resistance.

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Transcriptomic analysis of inter- and intra-patient variation in human iPSC cardiomyocytes: Platform for precision medicine to predict drug toxicity

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2016-08-24 | E-GEOD-83668 | biostudies-arrayexpress

Genome-wide DNA methylation change due to lncRNA H19 knockdown in myotubes

Project description:We used Methyl-MiniSeq platform from Zymo Research company to identify genome-wide methylation changes affected by lncRNA H19 knockdown in myotubes. Following H19 knockdown, we observed extensive genome-wide mthylation pattern changes relative to siCon cells, with some genes showing incresed methylation, others showing decreased methylation, and a third group with no significant change. Myotubes differentiated from mouse C3H myoblasts were transfected with either control siRNA or siH19, 48h later, cellular genomic DNA was extracted and subjected to genome-scale DNA methylation mapping using the platform of an improved version of Reduced Representation Bisulfite Sequencing (RRBS).

2015-11-09 | E-GEOD-73013 | biostudies-arrayexpress

A high dimensional deep sequencing study of non-small cell lung adenocarcinoma in never-smoker Korean females

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Tissue-specific transcriptomics, chromosomal localization, and phylogeny of chemosensory and odorant binding proteins from the red flour beetle Tribolium castaneum reveal subgroup specificities for olfaction or more general functions

Project description:Chemoreception is based on the senses of smell and taste that are crucial for animals to find new food sources, shelter, and mates. The initial step in olfaction involves the translocation of odorants from the periphery through the aqueous lymph of the olfactory sensilla to the odorant receptors by chemosensory proteins (CSPs) or odorant binding proteins (OBPs).To better understand the roles of CSPs and OBPs in a coleopteran pest species, the red flour beetle Tribolium castaneum (Coleoptera, Tenebrionidae), we performed transcriptome analyses of male and female antennae, heads, mouthparts, legs, and bodies, which revealed that all 20 CSPs and 49 of the 50 previously annotated OBPs are transcribed. Only six of the 20 CSP are significantly transcriptionally enriched in the main chemosensory tissues (antenna and/or mouthparts), whereas of the OBPs all eight members of the antenna binding proteins II (ABPII) subgroup, 18 of the 20 classic OBP subgroup, the C+OBP, and only five of the 21 C-OBPs show increased chemosensory tissue expression. By MALDI-TOF-TOF MS protein fingerprinting, we confirmed three CSPs, four ABPIIs, three classic OBPs, and four C-OBPs in the antennae.Most of the classic OBPs and all ABPIIs are involved in chemoreception. A few are also present in other tissues like odoriferous glands and testes and may be involved in release or transfer of chemical signals. The majority of the CSPs as well as the C-OBPs are not enriched in antennae or mouthparts, suggesting a more general role in the transport of hydrophobic molecules. RNAseq data obtained from different body parts of adult males and females, as well as larvae

2015-03-01 | E-GEOD-63162 | biostudies-arrayexpress

DNA sequencing comparing different stages of leukemic progression in a mouse model of severe congenital neutropenia (SCN)

Project description:To address how Csf3r and RUNX1 mutations in combination with CSF3 administration affect hematopoiesis in vivo, we performed serial transplantation experiments. Lineage-negative Csfr-d715 BM cell cells were lentivirally transduced with the patient specific RUNX1-D171N (RHD) mutant or an empty vector control. Primary recipients showed a pre-leukemic condition characterised by myeloblasts in the peripheral blood, but not overt AML. Upon serial transplantation, one of the Csfr-d715/RUNX1-D171N mutant mice, treated with CSF3, could repopulate secondary and tertiary recipients. Whole exome sequencing on these mice were performed to investigate whether these mice acquired an additional mutation. Enzymatically fragmented genomic DNA was used to construct sample libraries following the SeqCap EZ HyperPlusCap workflow User’s Guide version 1.0 (Roche). Unique, dual index adapters (Integrated DNA technologies) were used for ligation. After ligation of adapters and an amplification step, exome target sequences were captured using in-solution oligonucleotide baits (SeqCap EZ Developer Library mm9_exome_L2R_D02). Amplified captured sample libraries were paired-end sequenced on the HiSeq 2500 platform (Illumina).

2020-08-24 | E-MTAB-9376 | biostudies-arrayexpress

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