14666 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

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• H3Africa Chip Design - Aim of designing a cost-effective GWAS chip with content appropriate for use in genomics studies of individuals from the African continent.

  Since it is recognized that currently available chips may not be ideally suited to studying African populations, the H3Africa Genome Analysis working group undertook the task of designing a cost-effective GWAS chip with content appropriate for use in genomics research studies of individuals from the African continent. To address gaps in sequence data for some of the African populations being studied in H3Africa projects, a high coverage whole genome sequence dataset was generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health. This dataset includes 350 high coverage and 160 medium coverage whole genome sequences from 348 populations. The data is accompanied by minimal metadata, including country, ethnic group and sex.

  Study EGAS00001002976

• Comparison_of_transcriptional_response_of_induced_pluripotent_stem__iPS__cell_derived_and_monocyte_derived_macrophages_to_bacterial_lipopolysaccharide_stimulation

  In the first part of this project, we will differentiate IPS cells from 5 human donors into macrophages, and extract RNA from unstimulated and LPS stimulated macrophages to perform RNA sequencing. We will also extract RNA before and after stimulation in blood- derived macrophages from 5 additional, unrelated healthy samples. In the second part of the project, RNA-seq data will be analysed to compare LPS response of these two macrophage populations. In summary, we will perform 75bp PE RNA-seq on 20 samples (10 pre and post stimulus), on the HiSeq 2500 platform. Samples will be multiplexed at 5 samples / lane, so we will require 4 flow cells in total.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000563

• Acquisition_of_additional_mutations_drives_accelerated_progression_of_NPM1_positive_CMML_to_AML_

  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/We performed exome sequencing on serial samples from a patient with CMML who progressed to AML. The exome sequencing suggests that NPM1, TET2 and DNMT3a mutations were present in the dominant clone in the CMML sample and that NRAS is a new subclonal mutation in the AML sample. Diagnostic data shows the presence of a FLT3-ITD mutation in the AML sample, which is likely to have driven progression. Here we are performing re-sequencing of the putative driver and some passenger mutations which appear to be in the same clone to validate these mutations and to verify the relative quantification of these abnormalities .

  Study EGAS00001000619

• Spatial and temporal diversity in genomic instability processes define early stage lung cancer evolution.

  Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing on 25 regions from seven early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes, demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a proportional decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. We observed genome-doubling events early in tumor development of ex-smokers, suggesting prolonged latency periods before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.

  Study EGAS00001000840

• CRLF2_sequencing_project_Exomes

  I hope to gain insight into novel genetic aberrations present in these patients that will highlight important pathways that are involved in this subtype of leukaemia. It would be interesting to see if the mutations and pathways that are activated are consistent between the patients, or differences are observed dependent upon whether the patient has the translocation or the PAR1 deletion. Of note is the high association with either numerical gains of chromosome X or numerical/structural abnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. I hope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. By including the three patients that are normal for CRLF2, but have consistent genetic abnormalities found in the experimental cohort, I expect to find genetic differences between these two groups that will help us to identify novel molecular targets specific to CRLF2 deregulation.

  Study EGAS00001000081

• High coverage target resequencing of coding and regulatory regions of 38 Parkinson disease genes associated either to the Mendelian or the sporadic forms of the disease

  Coding sequences and putative regulatory sequences (retrieved from Ensembl and including up to 2500 bp of promoter sequence upstream the transcription start site) were re-sequenced to a mean depth of 49X on 38 genes associated to Parkinson's disease (RAB25, NUCKS1, RAB7L1, GBA, SYT11, ACMSD, STK39, MCCC1, STBD1, GAK, DGKQ, BST1, SCARB2, HLA-DRB5, GPNMB, FGF20, ITGA8, HIP1R, STX1B, SETD1A, SREBF1, MED13, RAI1, MAPT, RIT2, GIGYF2, HTRA2, EIF4G1, SNCA, LRRK2, VPS35, PINK1, DJ1, ATP13A2, UCHL1, PARK2, FBXO7, and PLA2G6). Sequencing was performed on 249 Parkinson's idiopathic cases and 145 unrelated controls of Spanish origin. All sequencing data was generated with an Illumina Hiseq2000 instrument after enrichment with a custom NimbleGen array. Raw reads were mapped to human reference genome hg19/GRCh37 using BWA aligner.

  Study EGAS00001000973

• Spatial heterogeneity in medulloblastoma

  Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor,which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.

  Study EGAS00001001014

• Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci

  Multiple regulatory elements distant to their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we have developed a capture Hi-C (cHi-C) approach to allow an agnostic characterisation of these physical interactions on a genome-wide scale. Single nucleotide polymorphisms associated with complex diseases often reside within regulatory elements and exert effects through long-range regulation of gene expression. Applying this cHi-C approach to 14 colorectal cancer risk loci has allowed us to identify key long-range chromatin interactions in cis and trans involving these loci.

  Study EGAS00001001085

• DNA methylation and somatic mutations converge on cell cycle and define similar evolutionary histories in brain tumors

  The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to the stability of genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetics can be similarly used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution.

  Study EGAS00001001255

• Investigate the evolutionary trajectories during invasiveness acquisition in early lung adenocarcinoma

  The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.

  Study EGAS00001004754