19431 results for "Cheap fc 26 coins Buyfc26coins.com is official EA Sports partner for FC 26 coins That was the fastest delivery ever..fxB4"

in 18.12 milliseconds.

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Mediators of Atherosclerosis in South Asians Living in America Study (MASALA)

  Cohort Description The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is a prospective cohort of South Asians that aims to identify risk factors for heart disease in a large, growing Asian American subgroup. MASALA enrolled 906 South Asians in 2010-2013 and then added a new wave of 258 South Asian participants from 2017-2018, for a full cohort size of 1,164. Data Being Submitted Wave 1 questionnaire data includes 3967 variables for up to 431 MASALA participants in C4R. Wave 2 questionnaire data includes 448 variables for up to 313 MASALA participants in C4R. Dried Blood Spot/Serosurvey data includes 7 variables for up to 248 MASALA participants in C4R. Derived data includes 43 variables for up to 528 MASALA participants in C4R. Phenotype data includes 113 variables for up to 429 MASALA participants in C4R.

  Study phs002980

• Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation

  An individual with acute myeloid leukemia (AML) received peripheral blood stem cell (PBSC) transplantation, but later experienced relapse. Whole-exome sequencing of bone marrow cells obtained from different stages of this patient as well as PBSC of the donor revealed that relapsed AML was not the regrowth of the original leukemic clones, but donor cell leukemia (DCL). Interestingly, some of the oncogenic mutations found in DCL were already present at a low frequency in the donor PBSC. Target deep sequencing of these genes indeed confirmed this observation, and revealed that the emergence of additional oncogenic mutations triggered leukemic evolution.

  Study JGAS000017

• Genomic Answers for Kids (GA4K)

  Identification of complex genetic variants including defects in gene regulatory circuits and uncharacterized genes present challenges for rare disease diagnosis. In Genomic Answers for Kids program we apply the joint interpretation of patient genome sequence with genomic endophenotypes to expand the clinically actionable genome among pediatric cases of suspected genetic disease. Our objective is to examine the role of novel and under-interpreted sequence variation by combining complete DNA sequences, personal epigenetic variations and massively parallel functional screens. To achieve this we perform augmented whole genome sequence (WGS) interpretation including reanalysis of clinical exomes as well as generating WGS for patients with negative exome results all be subject to family-based semi-automated recall pipeline to discover missed diagnostic variation. We use linked-read and long-read sequencing technologies to focus on putative structural variants missed in short-read genome and exome analysis by the optimized integration of linked and long read technologies that also improve identification of transmission patterns of all variants, as well as resolving genomic regions resistant to standard alignment. We also include tissue DNA sequencing to investigate somatic mosaicism. To further assist with WGS interpretation for uncommon variation we capture snapshots of patient transcriptomes and epigenomes in individual cells using single-cell RNA (scRNA) and sc open chromatin (scATAC) as well as bulk whole genome bisulphite genome sequencing for methylome interpretation. Alternative splicing is functionally assessed in available patient tissues using RNA-seq, including full length cDNA sequences by IsoSeq (PacBio) methodology. Our overarching goal is an increase rate of diagnostic genomic findings up to two-fold among rare disease, resulting in the majority (>50%) of patient cases resolved by the integrated system developed in our program.

  Study phs002206

• Identification of rare germline variants in familial multiple myeloma

  The risk of developing multiple myeloma (MM) in first-degree relatives of affected individuals is 2 to 4 fold higher than in the general population, implying the existence of inherited susceptibility. While over 20 common, low-penetrance variants have been associated with MM risk, less is known about rare, high-penetrance germline predisposition. We aimed to identify and characterize high/moderated penetrance germline variants in MM families using whole genome sequencing. For that purpose we identified families with at least two individuals diagnosed with MM or its precursors MGUS and smoldering MM. Also, patients with solitary plasmacytoma and AL amyloidosis were enrolled. We also recruited unaffected family members, and they were screened to exclude undetected MM or its precursor stages. After whole genome sequencing of blood DNA and filtering for rare variants (minor allele frequency <0.1%) and family segregation, variants are prioritized by a range of published in silico tools and literature search. The most promising variants are subjected to experimental validation to evaluate their functional relevance. Our data will provide guidance to worldwide efforts to unravel germline predisposition in MM and validation of the proposed variants and genes.

  Study EGAS00001004734

• Integration of Genomics and Transcriptomics in unselected Twins and in Major Depression

  Our goals are to develop a comprehensive understanding of the genomics of transcription in a population based unselected sample and to discover DNA and RNA biomarkers for major depressive disorder (MDD). This work is essential to developing a more complete understanding of the biological basis of MDD, a common complex trait associated with considerable morbidity, mortality, and personal/societal cost. All biological samples have been collected from well-defined populations, and are now available. First, we conduct a "genetical genomics" or eQTL study of ~800 MZ and ~800DZ twin pairs. Each subject has been assayed for genome-wide SNPs and CNVs and gene expression from peripheral blood sampled under standardized conditions. We determine the genetic architecture (genetic and non-genetic proportions of variance via twin analyses) for every transcript, and the genome-wide associations (i.e., SNP-transcript eQTL pairs). These analyses will be expanded to consider transcriptional modules. The key deliverable is a detailed catalogue of the general and specific architecture of transcription plus raw intensity files. Second, we seek to discover DNA and RNA biomarkers relevant to MDD, capitalizing on the results of a large MDD study with repeated clinical and biological assessments; we have previously shown that PB is a reasonable proxy for CNS expression and employ an advanced modelling framework: (a) Using baseline data, we identify biomarkers for MDD by comparing ~1000 controls with ~1400 MDD cases via comparisons of SNP, CNV, expression transcripts, and transcriptional modules. (b) Using longitudinal data, we contrast gene expression signatures assessed at baseline and two years later in ~200 controls and ~500 MDD cases.

  Study phs000486

• Single cell resolution landscape of hypomutated childhood cancers

  A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We found that apparent hypomutation was the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged.

  Dataset EGAD00001015406

• Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs

  We profile the adult human CNS from distinct regions, sex and ages, for chromatin accessibility at the single-nuclei level. Tissue was collected from 20 different donors (10 male, 10 female) within the ages of 34 to 74 years old. Additionally we performed Single-cell nanoCUT&Tag H3K27ac and H3K27me3 profiling for 4 of the donors and multiome single cell assay (RNA-seq+ATAC-seq) for 2 of the donors. Each donor donated fresh frozen white matter from the following three tissue regions: primary motor cortex (Brodmann area 4, BA4), arbor vitae cerebelli (CB) and fasciculi cuneatus and gracilis from and cervical spinal cord (CSC). Tissue was processed semi-randomly, ensuring that each batch of experiments had a representation of both sexes and all three tissue regions. Completed libraries were again randomly multiplexed during sequencing to minimize batch effects. We also performed micro-C,2 replicates, of iPS human derived cell cultures of human oligodendrocyte precursor cells (hOPC).

  Dataset EGAD50000000410

• Whole exome sequencing of non-small cell lung cancer patient-derived xenografts

  Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbour actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. We generated NSCLC patient-derived xenografts (PDXs) that recapitulate the histology and molecular features of primary NSCLC. Here, we completed whole exome sequencing on 122 NSCLC PDXs.

  Dataset EGAD00001008601

• CD8-targeted IL-2 unleashes tumor-specific immunity in human cancer tissue by reviving the dysfunctional T cell pool

  Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune checkpoint blockade can restore antitumor T cell function in some patients, however most do not respond to this therapy, often despite T cell infiltration in their tumors. We here explored a CD8-targeted IL-2 fusion molecule (CD8-IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8-IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8-IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8-IL2 was able to functionally reinvigorate T cells in tumors resistant to anti-PD-1, underscoring its potential as a novel treatment strategy for cancer patients.

  Study EGAS00001007712

• Whole Exome Sequencing of Diffuse Large B-Cell Lymphoma

  We performed massively parallel whole exome sequencing of 55 primary tumor samples from patients with diffuse large B cell lymphoma (DLBCL) and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, as well as in genes for which a functional role in DLBCL has not been previously suspected. Significantly mutated genes include MYD88, CARD11, EZH2, CREBBP, as well as MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO and TNFRSF14. Analysis of somatic mutations in patients with DLBCL also revealed that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, likely caused by activation-induced cytidine deaminase (AID)-mediated somatic hypermutation, and those non-synonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. We further identified genes with mutations that are likely to be functionally relevant despite being mutated at a low rate. These genes include KRAS, BRAF and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients.In order to facilitate additional in vitro and in vivo analyses of the discrete molecular clusters and associated targeted therapies in preclinical models, we also performed our subtyping analysis on 28 Diffuse Large B-Cell Lymphoma (DLBCL) cell lines. We performed whole exome sequencing (WES) on these cell lines to capture structural variants (SVs), from which we obtained full genetic characterization and segregation of these cell lines into our previously defined molecular clusters by DLBclass assignment. These analyses are available in an interactive DLBclass portal available to the public. Our data provide an unbiased view of the landscape of mutations in DLBCL. These data may point towards new targets for the treatment of DLBCL.

  Study phs000450