12405 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

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• Exome sequencing demonstrates a dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

  Retinoic acid (RA) and arsenic target the PML/RARA driver of Acute Promyelocytic Leukemia (APL), their combination now curing over 95% patients. Here we report exome sequencing of 64 matched diagnosis/remission/relapses patients treated with historical RA/chemotherapy protocols. A first subgroup presents a high incidence of oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that relapses derive from pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.

  Study EGAS00001002893

• Automated image-based profiling of complex drug induced phenotypes in patient-derived organoids

  We established a platform for high-throughput confocal fluorescence microscopy and automated image analysis to perform large-scale drug response profiling with patient derived organoids (PDOs). Using PDO lines newly established from colorectal cancer patients with a standardized workflow, we performed chemical perturbations with more than 500 experimental and clinically used compounds. Subsequently, we captured approx. six million images by confocal microscopy. To analyze drug-induced PDO re-organization on a single organoid level we developed SCOPE, a software framework for automated PDO high-throughput image analysis. We observed a rich variety of divergent and reoccurring compound induced phenotypes in organoids. Perturbation of cellular processes, including signaling by MEK, GSK3β, cyclin dependent kinases (CDKs) and others, led to recurring and distinct architectural changes. Highlighting the clinical relevance, PDO viability was heterogeneous after perturbation with anticancer drugs and matched clinical response of corresponding colorectal cancer patients. Our work opens new avenues for image-based profiling for accelerated drug discovery and clinical decision-making.

  Study EGAS00001003140

• Whole Exome Sequences of Human Embryonic Stem Cell Lines

  Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole exomes of widely available hESCs. The data generated has provided new insights about the nature of acquired variation and the genomic integrity of the cell lines. We anticipate that this online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease and trait-associated genetic variants.

  Study phs001343

• Genomic and Genetic Characterization of Prostate Tumors Treated with Neoadjuvant Intense Androgen Deprivation Therapy

  The purpose of this study was to develop better ways of detecting prostate cancer before and after pre-operative treatment, and to test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide. In this study, patients with intermediate and high risk prostate cancer received six months of neoadjuvant intense androgen deprivation therapy prior to radical prostatectomy. Biopsies were acquired prior to treatment. Tissue from biopsy and radical prostatectomy were subjected to sequencing and analysis for determination of features associated with response or resistance to treatment.

  Study phs001938

• NHLBI TOPMed - NHGRI CCDG: Massachusetts General Hospital (MGH) Atrial Fibrillation Study

  The Massachusetts General Hospital (MGH) Atrial Fibrillation Study was initiated in 2001. The study has enrolled serial probands, unaffected and affected family members with atrial fibrillation. At enrollment participants undergo a structured interview to systematically capture their past medical history, AF treatments, and family history. An electrocardiogram is performed; the results of an echocardiogram are obtained; and blood samples are obtained. For the TOPMed WGS project only early-onset atrial fibrillation cases were sequenced. Early-onset atrial fibrillation was defined as an age of onset prior to 66 years of age. Comprehensive phenotypic and pedigree data for study participants are available through dbGaP phs001001.

  Study phs001062

• Ribosomal Depleted Total RNA-Seq of PBMCs and Skin from Controls and Systemic Sclerosis Patients

  This study involved prospective collection of skin biopsies and peripheral blood mononuclear cell (PBMC) samples from controls with no self-reported history of autoimmune or inflammatory disease and cases with Rheumatologist-confirmed systemic sclerosis: limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), very early diagnosis of systemic sclerosis (VEDOSS), and systemic sclerosis sine scleroderma (SSS). Some SSc cases were sampled at a 6 month routine follow-up visit. PBMCs were collected and lysed immediately. Skin punches were stabilized in RNAlater until extraction. All RNA-Seq libraries were created using Takara/Clontech ribosomal depletion kits, and sequenced on either a HiSeq2500 or HiSeq3000.

  Study phs002902

• Primary central nervous system lymphoma (PCNSL) biopsies show heterogeneity in gene expression profiles, genetic subtypes, and in vitro drug sensitivity to kinase inhibitors

  Primary central nervous system lymphoma (PCNSL) is an aggressive large B-cell lymphoma, most often of the activated B cell (ABC) subtype, but with limited tumor biology studies due to small biopsy size and lack of strict cohort definition. Here we examined the genetic heterogeneity of 29 HIV- EBV- PCNSL tumors using whole exome sequencing (WES). We compared these tumors to 5 cell lines comprised of two human PCNSL cell lines (TK and HKBML) and three systemic activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (OCI-Ly3, TMD-8, HBL-1).

  Study EGAS50000000312

• Peripheral blood RNA sequencing of samples for a healthy cohort and a cohort with cancer patients

  RNA sequencing (fastq files) of white blood cells (WBCs) from healthy donors (n=376) and cancer patients (n=421) with different diagnoses, stages of disease and previously administered treatments, was performed. Samples from cancer patients were collected from the BostonGene clinical program; all patients provided written consent per IRB-approved protocols. Blood samples from healthy donors were purchased from multiple collection centers throughout the United States. Whole blood samples (3 ml) in K2-EDTA tubes received within 24 hours of collection at RT underwent red blood cell (RBC) lysis to isolate WBCs. Isolated WBCs for RNA sequencing were centrifuged at 300 x g for 5 minutes with a maximum of 10^6 cells per vial. The supernatant was removed, and the cells were resuspended in cold Homogenization Buffer (2% 1-Thioglycerol, Promega). Samples were then frozen at -80°C until extraction. RNA extraction was performed from frozen samples with Maxwell RSC simplyRNA Cells Kit (Promega) using the benchtop automated Maxwell RSC Instrument (Promega). Libraries were prepared with Illumina TruSeq® Stranded mRNA Library Prep (Poly-A mRNA; stranded). Libraries were sequenced on NovaSeq 6000 as Paired-End Reads (2x150) with targeted coverage of 50 mln reads.

  Dataset EGAD50000000414

• Assessing Individual Head and Neck Squamous Cell Carcinoma Patient Response to Therapy Through Integration of Functional and Genomic Data

  This study combines RNA sequencing (RNASeq), whole exome sequencing (WES), reverse phase protein array (RPPA) and copy number variation (CNV) data, along with a custom high throughput inhibitor assay to characterize tumor cells from patients with head and neck squamous cell carcinoma (HNSCC), in order to identify potential therapy targets on an individual patient basis. The data that will be available through dbGaP include the RNASeq, WES, RPPA and array CNV data for the tumor and matched normal samples. This study represents a proof-of-concept. No treatments were administered to patients as part of this study.

  Study phs003456

• Single-Cell Transcriptomic Characterization of Microscopic Colitis

  Patients with microscopic colitis (MC), chronic diarrhea without histological signs of MC, or unaffected controls were profiled using single-cell RNA sequencing (scRNA-seq; inDrops and 10X Genomics were used). One profiled patient without clinical symptoms was found to have histological signs of MC (asymptomatic MC). Some of the subjects from dbGaP study phs003418 are controls in this study. T-Cell Receptor sequencing (TCR-Seq) was also performed on a subset of patients. Individual transcriptomes were analyzed to characterize the cellular profile associated with MC and search for mediators of disease pathology. Raw reads and processed count matrices will be available through dbGaP.

  Study phs003876

• RNA Sequencing Analysis of Patient-Derived Xenograft Tissue PIM-084 Treated with L-NMMA+Alpelisib vs Vehicle Control

  This dataset contains RNA-seq analysis of vehicle control compared to L-NMMA+alpelisib treated metaplastic breast cancer PDX PIM084 tumors (RNA sequencing and analysis performed by Novogene). The submitted data contains the gene ID, gene name, normalized read counts from all samples from control group and combination treatment group, log2-fold change derived from DESeq2 R/EdgeR package, p-value, adjusted p-value, read counts from each group, and gene FPKM from the each sample in the group. Due to patient privacy, we are submitting only the processed and desensitized RNA sequencing analysis to this repository.

  Study phs003814

• Vitamin-D-Kids Asthma

  The Vitamin D Kids Asthma Study (VDKA) was a 48-week multicenter randomized, double-blinded, placebo-controlled trial of vitamin D3 for severe asthma exacerbations in children 6-16 years old, recruited from February 28, 2016 to September 20, 2019. An ancillary study for nasal sampling was conducted at the Pittsburgh site. Prior to randomization, participants completed questionnaires and underwent collection of nasal samples for gene expression studies. VDKA was approved by the IRBs of all participating institutions, and the ancillary study was approved by the IRB of the University of Pittsburgh. Written parental consent was obtained for participating children, from whom written assent was also obtained.

  Study phs004051

• Single-cell/single-nucleus RNA-seq of Embryonal Tumor with Multilayered Rosettes (ETMR)

  Embryonal tumor with multilayered rosettes (ETMR) is a pediatric brain tumor with dismal prognosis. We analyzed eleven ETMR patient samples using single-cell transcriptomics. We reveal a spatially distinct cellular hierarchy that spans highly proliferative neural stem-like cells and more differentiated neuron-like cells. C19MC is predominantly expressed in stem-like cells and controls a transcriptional network governing stemness and lineage commitment. Systematic analysis of receptor-ligand interactions between malignant cell types reveals FGFR and NOTCH signaling as oncogenic pathways. Our study provides fundamental insights into ETMR pathobiology and a powerful rationale for more effective targeted therapies.

  Study EGAS50000000937

• Development of molecular targeted therapy for small cell lung cancer by comprehensive genome analysis

  Aims: Identifying new therapeutic targets of small cell lung cancer (SCLC), genome-wide mutation analysis has been performed. Methods: Genomic DNA was extracted from formalin-fixed or methanol-fixed tissue samples. 71 Mb of DNA fragments containing whole coding exons were concentrated using SureSelect Human All Exon V4+UTRs Kit (Agilent Technologies) followed by 100-bp paired end sequencing by HiSeq 2000 (Illumina). Participants/Materials: 51 of 1042 cases of pathologically diagnosed small seen lung cancer that were registered to National Cancer Hospital East Lung Cancer Database in 1992-2012, and which surgically resected or biopsy samples were suitable for DNA extraction for further analyses.

  Study JGAS000037

• The evolutionary landscape of colorectal tumorigenesis

  The genetic events that cause colorectal adenomas to progress to carcinomas remain largely undetermined. Using multi-region genome/exome sequencing of 24 benign and malignant colorectal tumours, we probe the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations, hence lack selective sweeps, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas not by nucleotide-level mutations (drivers or burden), but by widespread aneusomies that are usually clonal and often accrue in a “punctuated” fashion. Adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilising selection.

  Study EGAS00001003066

• Genome Wide Association Study:GR@ACE Stage I

  The Genome Research program at Fundacio ACE (GR@ACE, Barcelona, Spain), represents a new effort to study Alzheimer's Disease susceptibility. The GR@ACE study comprises 7,409 unrelated individuals. 4,120 AD cases were diagnosed at Fundació ACE Memory Clinic (Barcelona, Spain). 3,289 Controls were obtained from three collections (Fundació ACE, Barcelona; DNA National Biobank, Salamanca and HU Valme, Seville). Genotyping was carried out using the 815K Axiom Spain Biobank array (Affymetrix.) in the Spanish national center for genotyping (CEGEN, Santiago de Compostela, Spain). After genotyping, an extensive quality control was conducted, including re-sampling, gender match, stratification, relatedness, heterozygosity, differential missingness and HWD analyses.

  Study EGAS00001003424

• Exome-wide somatic mutation characterization of small bowel adenocarcinoma

  Small intestinal adenocarcinoma (SIA) is a rare and aggressive form of cancer with limited treatment options. To further characterize the somatic mutation landscape of this tumor type, exome sequencing was conducted on a population-based set of SIA samples from all three parts of the small intestine. Archival tissue from 106 tumors with comprehensive clinical patient information entered exome sequencing from a patient series consisting of SIA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify significantly mutated genes from the exome data. Also mutational signature and pathway enrichment analyses were performed.

  Study EGAS00001002559

• WGS___Exploration_of__mutational_processes_in_human_cancer_cell_lines

  Approximately 25 cell lines representative of 11 mutation signatures have been selected and will be grown from a single cell, referred to as parental clone, for a period of 3 months to allow accumulation of mutations. Following that period, we will obtain 2 subclones from each of the parental clone for analysis by exome-sequencing . In total we will therefore be sequencing 2 parental clones and 4 subclones per cell line for approximately 25 cell lines. Once the data has been analysed and the potential ongoing mutation processes determined, we will perform whole-genome sequencing of the parental clones and subclones of the candidate cell lines.

  Study EGAS00001002680

• PTPN22 SNPs and outcome after lung transplantation

  Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 144 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed.

  Study EGAS00001003380

• Mutational landscape of renal cell carcinoma with venous tumor thrombus

  Renal cell carcinoma with venous tumor thrombus opens the unique opportunity to investigate the clonal evolution of a tumor in two fundamentally different compartments i.e., within the confinement of an organ and inside a large blood vessel. We performed multiregion whole exome sequencing of a total of 37 samples from five consecutive patients (normal tissue, n=5; primary tumors, n=16; tumor thrombi, n=16) to >35-fold target coverage. Four patients had a clear cell RCC, one patient had a poorly differentiated type II papillary RCC (RCC-VTT-04). The latter patient had a friable thrombus, the others were of solid consistency.

  Study EGAS00001001950

• High titers and low fucosylation of early phase anti-SARS-CoV-2 IgG promote hyper-inflammation by alveolar macrophages

  We show that early phase anti-Spike IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for severe COVID-19. First, inflammation is driven by high titers of anti-Spike IgG, a hallmark of severe disease. Second, we found that anti-Spike IgG from severely ill patients is intrinsically more pro-inflammatory because of different glycosylation of the Fc tail, particularly by low fucosylation. This dataset is linked with the following ArrayExpress Experiment: E-MTAB-10431 - 2020_COVID19_FCGR_MIL10_IgGfucosylation

  Study EGAS00001005206

• The Haplotype Reference Consortium

  The Haplotype Reference Consortium (HRC) will create a large reference panel of human haplotypes by combining together sequencing data from multiple cohorts. By combining together multiple cohorts, the reference panels produced by the project will be as large as possible in terms of both number of haplotypes, and numbers of variants. This will increase the accuracy of the genotype imputation, especially at low-frequency variants, and the number of imputable variants, thus increasing the power of GWAS.

  Study EGAS00001001710

• GWAS Results from Danjou et al, Nature Genetics 2015

  We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.

  Study EGAS00001003645

• RNA sequencing data of 257 samples from the CORALLEEN trial

  Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x)

  Dataset EGAD00001010121

• Partner independent fusion gene detection by multiplexed CRISPR Cas9 enrichment and long read Nanopore sequencing (FUDGE)

  Targeted long-read nanopore sequencing. Abstract: Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. To accurately and impartially identify fusions, we developed FUDGE: FUsion Detection from Gene Enrichment. FUDGE couples target-selected and strand-specific CRISPR/Cas9 activity for fusion gene driver enrichment - without prior knowledge of fusion partner or breakpoint-location – to long-read Nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints - within two days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay, providing unparalleled opportunity for diagnostic pan-cancer fusion detection.

  Dataset EGAD00001006111