11057 results for "fc 26 best way to get coins Visit Buyfc26coins.com Gyors és hatékony szolgáltatás. Hamarosan visszatérek több FC 26 érmeért..4w1a"

in 25.99 milliseconds.

• Novel CNV contribution to schizophrenia from a genome wide study of 41,321 subjects

  Genomic copy number variants (CNVs) have been strongly implicated in the etiology schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the very low frequencies of risk alleles, all occurring in less than 1% of patients. We sought to address this obstacle through a collaborative effort unprecedented in psychiatry in which we applied a centralized analysis pipeline to a large SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden is observed in SCZ patients (OR=1.11, P=5.7e-15), and persists after excluding loci implicated in previous studies (OR=1.07, P=1.7e-6). CNV Burden is also enriched for genes associated with synaptic function (OR = 1.68, P = 2.8e-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3e-05). While only previously implicated loci surpass strict genome-wide testing correction, we identify “novel” CNVs (BH-FDR < 0.05) that confer both protective and risk effects on SCZ and are predominantly mediated by non-allelic homologous recombination (NAHR). Our combined data find genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2.

  Study EGAS00001001960

• Resistance to anti-EGFR therapy in colorectal cancer

  Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we performed whole genome sequencing of plasma DNA (plasma-Seq) from patients treated with anti-EGFR therapy. We demonstrate that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. However, we also show that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy. In contrast, employing ultra-sensitive deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR, we did not observe the occurrence of novel, acquired mutations. Overall, whole-genome plasma DNA sequencing represents a non-invasive blood-based surrogate measure of changes in tumors. As such, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.

  Study EGAS00001000582

• The double-hit signature identifies double-hit diffuse large B-cell lymphoma with genetic events cryptic to FISH​

  High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/THs) include a group of diffuse large B-cell lymphomas (DLBCLs) with inferior outcomes after standard chemoimmunotherapy. We recently described a gene expression signature that identifies 27% of germinal center B-cell DLBCLs (GCB-DLBCLs) as having a double-hit-like expression pattern (DHITsig) and inferior outcomes; however, only half of these cases have both MYC and BCL2 translocations identifiable using standard breakapart fluorescence in situ hybridization (FISH). Here, 20 DHITsig+ GCB-DLBCLs apparently lacking MYC and/or BCL2 rearrangements underwent whole-genome sequencing. This revealed 6 tumors with MYC or BCL2 rearrangements that were cryptic to breakapart FISH. Copy-number analysis identified 3 tumors with MYC and 6 tumors with MIR17HG gains or amplifications, both of which may contribute to dysregulation of MYC and its downstream pathways. Focal deletions of the PVT1 promoter were observed exclusively among DHITsig+ tumors lacking MYC translocations; this may also contribute to MYC overexpression. These results highlight that FISH fails to identify all HGBL-DH/THs, while revealing a range of other genetic mechanisms potentially underlying MYC dysregulation in DHITsig+ DLBCL, suggesting that gene expression profiling is more sensitive for identifying the biology underlying poor outcomes in GCB-DLBCL.

  Study EGAS00001004285

• ATAC-seq of a selected group of AML cases

  ATAC-seq data were generated for a number of selected patients to investigate changes in enhancer and promoter regions. ATAC-seq was essentially carried out as described in31. Briefly, prior to transposition the viability of the cells was assessed and 1 × 106 cells were treated in culture medium with DNase I (Sigma) at a final concentration of 200 U ml−1 for 30 minutes at 37 °C. After Dnase I treatment, cells were washed twice with ice-cold PBS, and cell viability and the corresponding cell count were assessed. 5 × 104 cells were aliquoted into a new tube and spun down at 500 × g for 5 minutes at 4 °C, before the supernatant was discarded completely. The cell pellet was resuspended in 50 µl of ATAC-RSB buffer (10 mM Tris-HCl pH 7.4, 10 mM NaCl, 3 mM MgCl2) containing 0.1% NP-40, 0.1% Tween-20, and 1% Digitonin (Promega), and was incubated on ice for 3 minutes to lyse the cells. Lysis was washed out with 1 ml of ATAC-RSB buffer containing 0.1% Tween-20. Nuclei were pelleted at 500 × g for 10 minutes at 4 °C. The supernatant was discarded carefully and the cell pellet was resuspended in 50 µl of transposition mixture (25 µl 2× tagment DNA buffer, 2.5 µl transposase (100 nM final; Illumina), 16.5 µl PBS, 0.5 µl 1% digitonin, 0.5 µl 10% Tween-20, 5 µl H2O) by pipetting up and down six times. The reaction was incubated at 37 °C for 30 minutes with mixing before the DNA was purified using the Monarch PCR & DNA Cleanup Kit (NEB) according to the manufacturer’s instructions. Purified DNA was eluted in 20 µl elution buffer (EB) and 10 µl purified sample was objected to a ten-cycle PCR amplification using Nextera i7- and i5-index primers (Illumina). Purification and size selection of the amplified DNA were carried out with Agencourt AMPure XP beads. For purification the ratio of sample to beads was set to 1:1.8, whereas for size selection the ratio was set to 1:0.55. Purified samples were eluted in 15 µl of EB. Quality and concentration of the generated ATAC libraries were analyzed using the High Sensitivity D1000 ScreenTape Kit (Agilent) and libraries were sequenced paired-end on a NovaSeq (Illumina). ATAC-seq reads were aligned to the human reference genome build hg19 with bowtie2

  Dataset EGAD00001007583

• Combination therapies for personalized cancer medicine

  It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.

  Dataset EGAD00001000869

• Whole Exome Sequencing for Colorectal Cancer

  This project was designed to use next generation sequencing technology to screen the protein coding regions of the genome for low frequency variants in a panel of high-risk colorectal adenocarcinoma cases. Blood and cell-line DNA for colorectal cancer patients and a subset of quality control samples that had existing whole exome sequence data were analyzed using Illumina HiSeq sequencers. Samples from this project were from participants in the Women's Health Initiative (WHI) and the Diet, Activity, and Lifestyle Study (DALS).

  Study phs000410

• The Mexican-American Coronary Artery Disease Study (MACAD)

  The MACAD Study, funded by NHLBI, was designed to explore genetic contributions to coronary artery disease and glucose homeostasis traits among Hispanics using a family-based design. The baseline examination of the cohort included the euglycemic hyperinsulinemic clamp test from which the two key phenotypes were obtained: insulin sensitivity (M) and metabolic clearance rate of insulin (MCRI). Genome-wide genotyping was obtained under separate funding by NIDDK as a part of the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.

  Study phs001397

• NHLBI TOPMed: Partners HealthCare Biobank

  The Atrial Fibrillation Genetics Consortium (AFGen) was organized to identify common and rare genetic variation associated with atrial fibrillation risk. In the current study, we have performed whole genome sequencing in cases with early-onset atrial fibrillation. Samples in this study were enrolled as a part of the Partners HealthCare Biobank. Cases with early-onset atrial fibrillation were identified from the Biobank (defined as atrial fibrillation onset prior to 61 years and in the absence of structural heart disease).

  Study phs001024

• NHLBI TOPMed: HyperGEN - Genetics of Left Ventricular (LV) Hypertrophy

  The Hypertension Genetic Epidemiology Network Study (HyperGEN) - Genetics of Left Ventricular (LV) Hypertrophy is a familial study aimed to understand genetic risk factors for LV hypertrophy by conducting genetic studies of continuous traits from echocardiography exams. The originating HyperGEN study aimed to understand genetic risk factors for hypertension. Data from detailed clinical exams as well as genotyping data for linkage studies, candidate gene studies and GWAS have been collected and is shared between HyperGEN and the ancillary HyperGEN - Genetics of LV Hypertrophy study.

  Study phs001293

• Comprehensive Analysis of Structural Variants in Breast Cancer Genomes Using Single Molecule Sequencing

  This study used the SKBR3 breast cell line and tumor/normal organoids derived from breast tissue to explore the utility of long read sequencing for detecting structural variants in complex samples. Three technologies were used to characterize the samples: Illumina/10X, Pacific Biosciences, and Oxford Nanopore. Methylation results were derived from the Oxford Nanopore data. It is hoped that this resource will better help researchers better understand the utility of long read sequencing in cancer samples.

  Study phs002210

• National Cancer Institute (NCI) Primary Human Melanocyte QTL Study

  In order to create a melanocyte-specific QTL resource, we obtained primary human melanocyte cultures isolated from foreskin of 106 healthy newborn males predominantly of European descent. Melanocytes were cultured in lot-matched culture medium in randomized batches to minimize variability that could be introduced by culturing conditions. RNA sequencing and direct SNP genotyping of these samples produced an average of ~87.9 million reads (paired-end, stranded, 126bps), and ~713,000 SNP genotypes, respectively. Illumina 450K methylation array covered over 485,000 CpGs distributed genome wide.

  Study phs001500

• Pharmacogenomics of Mercaptopurine Intolerance in Children with Acute Lymphoblastic Leukemia (AALL03N1)

  Mercaptopurine (MP) is the mainstay of curative therapy for acute lymphoblastic leukemia (ALL). We performed a genome-wide association study (GWAS) to comprehensively identify the genetic basis of MP intolerance in children with ALL in AALL03N1. MP dose intensity was defined as prescribed dose divided by the planned protocol dose during maintenance therapy.  Germline variants in NUDT15 and TPMT were found to be strongly associated with MP intolerance in childhood ALL, which may have implications for treatment individualization in this disease.

  Study phs002846

• DNA and RNA Profiling Using Simultaneous Sequencing (Simul-seq)

  Paired DNA and RNA profiling is increasingly employed in genomics research to uncover molecular mechanisms of disease and to explore personal genotype and phenotype correlations. We developed a novel simultaneous DNA and RNA sequencing approach (Simul-seq) that enables comprehensive genomic and transcriptomic profiles from small quantities of cells or tissues. In this study, Simul-seq was performed on patient-derived fibroblast cells as well as an esophageal adenocarcinoma tumor sample and compared with standard DNA and RNA-sequencing approaches.

  Study phs001214

• Genome Wide Association Study of Chronic TMD: Discovery Phase

  The OPPERA project is investigating effects of genetic, physiological, psychological and clinical factors on the risk of developing painful temporomandibular disorder (TMD). This case-control study is a discovery-phase genome wide association study that aims to identify commonly-occurring genetic variants associated with chronic TMD. It represents the first step in a series of studies that seek to identify the genetic background of TMD. For related phenotype and targeted genotype data, please see additional studies from the OPPERA project at dbGaP phs000761).

  Study phs000796

• NHLBI TOPMed: Children's Health Study (CHS) Integrative Genomics and Environmental Research of Asthma (IGERA)

  The Integrative Genomics and Environmental Research of Asthma (IGERA) Study was proposed to collect immortalized cell lines, RNA, cDNA and DNA from 400 well-characterized subjects who participated in the southern California Children's Health Study (CHS) and to develop an accompanying database for these samples consisting of extensive phenotype, exposure, genome-wide genotype, gene expression, and methylation data. A subset of Hispanic-White participants (n=160) were included in the TOPMed project, including 77 asthma cases and 83 controls.

  Study phs001603

• Breast Cancer Genome Guided Therapy Study (BEAUTY)

  The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant clinical study enrolling 140 women with Stage I-III breast cancer. The goals of this study were to 1) perform comprehensive sequencing of germline and tumor tissues (exome and RNA seq), 2) identify genomic alterations and perturbed pathways associated with response/resistance to standard chemotherapy, and 3) develop patient-derived xenograft (PDX) for testing of therapeutic regimens chosen on the basis of alterations identified by genetic sequencing.

  Study phs001050

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): ILI Labels and Longitudinal Novel Engagement with Symptom Surveillance (ILLNESS) Study

  This study is a prospective observational study, approximately seven months in duration. Participants were asked to complete a weekly survey online asking about their ILI (influenza-like illness) experience over the past seven days. The primary objective of this study was to collect a population-wide, longitudinal dataset of ILI events (with onset and recovery dates) and the associated symptoms, behaviors, and medical information associated with each event.DOI: https://rapids.ll.mit.edu/10.57895/4vfb-4z30

  Study phs002538

• Human Vaccines Project: scRNAseq Characterization of HepB Vaccine Response

  In adult systems vaccinology studies, baseline immune status (i.e. pre-vaccine) of vaccine recipients was highly predictive of vaccine immunogenicity. The aim of this study is to characterize pre-vaccine immune signatures that predict immunogenicity of HBV in humans using single cell transcriptomics. To investigate the pre-vaccine status of these patients, we characterized transcriptomic responses in 5 FACS sorted populations of circulating immune cells, mDCs, monocytes, pDCs, natural killer cells and neutrophils, sample at baseline, 3, 7 and 14 days after vaccination.

  Study phs002508

• Segmental Overgrowth/Vascular Anomalies/Dermatologic Disorders

  This study was designed to determine the molecular etiology of disorders characterized by segmental overgrowth, vascular anomalies, or dermatologic conditions that are part of the diagnostic criteria for Proteus syndrome or PIK3CA-related overgrowth spectrum (PROS). Somatic variants in AKT1 or PIK3CA have been identified as causative for Proteus syndrome and PROS respectively, and this study aimed to determine the extent of allelic and genetic heterogeneity in individuals who fully met the diagnostic criteria, had some aspects of, or had isolated manifestations of either syndrome.

  Study phs002006

• Metatranscriptomic Sequencing of Pre-Transplant Bronchoalveolar Lavage in Pediatric Stem Cell Transplant Patients

  Children with malignancies, immunodeficiencies, and other life-threatening diseases sometimes receive allogeneic hematopoietic cell transplantation (HCT) as a treatment for their disease. The HCT process can be complicated by the development of lung disease from infection, alloreactivity, or other causes. To identify patients at-risk for post-HCT lung disease, this study uses metatranscriptomic RNA sequencing of bronchoalveolar lavage (BAL) obtained prior to HCT. Sequencing results are associated with the development of post-HCT lung injury. 

  Study phs002208

• Therapeutic Genetics and Disease Modeling in LAMA2-CMD

  Merosin-deficient congenital muscular dystrophy (MDC1A) is an autosomal recessive disorder caused by mutations in the LAMA2 gene, resulting in a defective form of the extracellular matrix protein laminin-α2 (LAMA2). Individuals diagnosed with MDC1A exhibit progressive muscle wasting and declining neuromuscular functions. No treatments for this disorder are currently available. This study involves transcriptomic comparison analysis between MDC1A patient fibroblasts and healthy control fibroblasts to reveal changes in gene expression that contribute to LAMA2 congenital muscular dystrophy (LAMA2-CMD).

  Study phs003250

• Genomic Analysis of Pre-Treatment and Autopsy Glioblastoma Specimens

  We performed whole exome sequencing data of pre-treatment glioblastoma specimens, matched to post-treatment recurrent intracranial autopsy samples and metastatic extracranial post-treatment autopsy samples. We identified early genetic events common to the evolutionary ancestry of both pre-treatment glioblastoma and later recurrences. We demonstrated that there were no protein-coding mutations as recurrent truncal events across the majority of the cohort. In contrast, we identified four truncal non-coding genomic alterations that likely represent the precursor cell population of glioblastoma.

  Study phs001424

• RB1 Loss Triggers Dependence on ESRRG in Retinoblastoma

  Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed whole exomes from primary Rb tumors to identify novel Rb dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in Rb pathogenesis. ESRRG is an essential mediator of hypoxic adaptation and cell survival in retinoblastoma, representing a promising new therapeutic target.

  Study phs002859

• The Hypertension-Insulin Resistance Family Study (HTN-IR)

  The HTN-IR Study, funded by NHLBI, was designed to explore genetic contributions to hypertension and glucose homeostasis traits among Hispanics using a family-based design. The baseline examination of the cohort included the euglycemic hyperinsulinemic clamp test from which the two key phenotypes were obtained: insulin sensitivity (M) and metabolic clearance rate of insulin (MCRI). Genome-wide genotyping was obtained under separate funding by NIDDK as a part of the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.

  Study phs001394

• VitGene Generalized Vitiligo Genetics Study-Phase 2

  Generalized vitiligo is an autoimmune disease in which melanocyte loss results in patchy depigmentation of skin and hair. For this third GWAS of generalized vitiligo, SNPs were genotyped in 1,059 generalized vitiligo cases of European-derived white (EUR) ancestry using the Illumina Human OmniExpress BeadChip array. The data were combined with those of Phase 1 and Phase 2 to provide at least 85% power to detect associations with OR > 1.22 at genome-wide significance (P = 5 x 10-8) for MAF > 0.25.

  Study phs000224