14478 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

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• Landscape of Somatic Mutations in B Lymphocytes Across Human Lifespan

  The accumulation of spontaneous mutations in somatic cells has been implicated as a cause of aging since 1950. Yet, attempts to establish a causal relationship between somatic mutations and aging have been constrained by the lack of methods to directly identify mutational events in primary human tissues. Using a highly accurate single-cell whole-genome sequencing method, we analyzed human B lymphocytes from donors varying in age from birth to over 100 years, studying both genome distribution and functional impact of base substitution mutations.

  Study phs001808

• Endometrial Cancer Association Consortium - OncoArray Genotypes

  The data come from 9 studies participating in the Endometrial Cancer Association Consortium (ECAC). ECAC data included in this dbGaP submission include OncoArray data from 4486 endometrial cancer cases genotyped at the Center for Inherited Disease Research (CIDR). Samples were genotyped using the Illumina OncoArray beadchip 500K SNP custom array. Details of the genotyping process and sample selection are included in O'Mara et al, Identification of nine new susceptibility loci for endometrial cancer. Nature Communications (PMID:30093612).

  Study phs001885

• Next Generation Mendelian Genetics: Kabuki Syndrome

  The ultimate purpose of this research is to identify genes causing hereditary disorders. We are scaling a new approach to identify the candidate genes and gene mutations that underlie rare human Mendelian (a set of primary tenets relating to the transmission of hereditary characteristics from parent to child) diseases by using exome (protein coding segments of DNA) resequencing. The exome sequences of ten unrelated individuals with a diagnosis of Kabuki Syndrome (OMIM: 147920) were obtained by massively parallel DNA sequencing.

  Study phs000295

• Disease Severity in Familial Dysautonomia

  Familial Dysautonomia (FD) is a developmental and degenerative genetic disease that manifests in the neural crest cells and peripheral nervous system (PNS). Despite all FD patients having the same mutation in IKBKAP, patients present with varying disease severity, ranging from mild to severe. We used the human pluripotent stem cell technology to recapitulate this varying disease severity in the dish. Further, we found that severe, but not mild patients harbor mutations in candidate modifier genes that may contribute to severe disease presentation.

  Study phs001233

• Bladder Chemotherapy Responders

  Cisplatin-based chemotherapy is the standard of care for patients with muscle invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, and some patients with metastatic disease achieve complete responses to these therapies. However, the molecular determinants of cisplatin response are incompletely understood. We performed whole exome sequencing on tumor and germline DNA from patients with muscle invasive or metastatic urothelial carcinoma who received cisplatin-based chemotherapy to identify somatic mutations that occurred preferentially in cisplatin responders.

  Study phs000771

• Genome Instability in Mammary Cells of Pathogenic BRCA1/2 Mutation Carriers

  It remains unknown if inherited germline mutations in the BRCA1 or BRCA2 gene increase the risk of breast and ovarian cancer by elevating mutation rate in mammary cells. Here we show, using a single-cell whole genome sequencing approach, that mammary luminal epithelial cells isolated from tissues obtained from preventive mastectomy surgeries in women with a pathogenic BRCA1/2 germline mutation, exhibit a statistically significant, increased mutation frequency as compared to age-matched controls without genetic risk of breast cancer.

  Study phs002411

• Oncogenomics of Malignant Peripheral Nerve Sheath Tumors

  Malignant peripheral nerve sheath tumors (MPNSTs) are a group of highly aggressive soft tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1-associated), or after radiotherapy (RT-associated). We utilized comprehensive genomic approaches and identified recurrent loss-of-function somatic alterations in the Polycomb repressive complex 2 (PRC2) core components EED or SUZ12. Genetic loss of either of these two genes results in complete loss of H3K27me3 and aberrant transcriptional programming in the affected tumors.

  Study phs000792

• Characterization of Neoantigen-reactive T cells by Single-Cell Analysis

  Through CITE-seq and TCR-seq analysis of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TIL), we developed a neoantigen-reactive T-cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. There are four datasets from four NSCLC cases. Each dataset includes (1) Transcriptome of tumor infiltrating lymphocytes (TIL), (2) Cell surface protein expression on TIL by Feature barcoding, (3) T-cell receptor analysis of TIL, and (4) Reference file for feature-barcoding antibodies.

  Study phs002792

• A Phenotypic and Genomics Approach in a Multi-Ethnic Cohort to Subtype Systemic Lupus Erythematosus

  Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems and varies in severity across different populations. To examine the clinical heterogeneity of SLE, we sought to identify different lupus subtypes within our multi-ethnic cohort using a clustering approach. Additionally, with genome-wide methylation and genotype data generated for our cohort, we applied integrative methods to investigate genetic and epigenetic risk factors. This integrative and computational approach revealed molecular differences associated with phenotypic clusters.

  Study phs001850

• Mutational Landscape of Lethal Castrate Resistant Prostate Cancer

  Exome sequencing of matched pairs of tumor / normal genomic DNA was performed from high risk localized prostate cancer or lethal, metastatic, castrate resistant prostate cancer (CRPC). Exome libraries were prepared using Illumina Paired_End Genome DNA Sample Prep Kit and captured using Agilent SureSelect Capture Library or Roche EZ Exome capture library. Sequencing was performed on Illumina GAII and HiSeq 2000 platforms in paired end mde, with 80 base pair reads from the final library fragments. Copy number alterations and somatic mutations were identified.

  Study phs000554

• Decade-Long Leukemia Remissions with Persistence of CD4+ CAR T-Cells

  Two patients with chronic lymphocytic leukemia (CLL) were treated with CD19 targeted CAR T therapy and followed over several years. Peripheral blood from both patients at multiple time points was collected, and 5' CITE-Seq with TCR profiling was performed on sorted CD3+CAR+ T cells at multiple time points. Here, we deposit the raw sequencing data for these single-cell experiments. Processed and de-identified data (e.g. cellranger output, Seurat objects) have been made available on a separate public data repository.

  Study phs002931

• Genomics and Modification of Pain: A peripheral component identified using iPSCs with the S241T mutation

  We have capitalized on inherited erythromelalgia (IEM) as a well-characterized genetic model of chronic pain, and studied IEM patients carrying Nav1.7 mutations which affect channel activation and often produce hyperexcitability of DRG neurons. Whole exome sequencing was used to discover multiple gene variants that might contribute to neuronal excitability and that might serve as modifiers of sensory neuron firing, and identified the Kv7.2 channel as a contributor to differences in pain profiles between individuals.

  Study phs001724

• Germline genome-wide association studies in women receiving neoadjuvant chemotherapy with or without bevacizumab on NSABP B-40

  Neoadjuvant chemotherapy (NAC) for breast cancer is widely employed. We performed genome-wide association studies (GWAS) to determine if germline genetic variability was associated with benefits, in terms of pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS), in patients entered on the NSABP B-40 NAC (National Surgical Adjuvant Breast and Bowel Project, B-40, Neoadjuvant Chemotherapy) trial where some patients were randomized to receive bevacizumab, in addition to chemotherapy.

  Study phs001365

• High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8+ T Cells

  We developed a high-dimensional, tetramer associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile cognate antigen specificities, TCR sequences, targeted gene-expression, and surface protein expression. Cultured antigen-specific CD8+ T cell clones were studied as a proof-of-concept experiment. In addition, both the antigen specific CD8+ T cells from healthy subjects and Type I diabetic patients were investigated. 18 individually consented subjects pooled into four groups for sample processing

  Study phs002441

• 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

• CCG Multicentric Italian Lung Detection (MILD)

  For the CCG-MILD project, NCI will utilize whole genome sequencing and/or whole exome sequencing in conjunction with transcriptome sequencing to try to identify recurrent genetic alterations (mutations, deletions, amplifications, rearrangements) and/or gene expression signatures that would be important to the hypothesis(es) submitted by the investigators. The samples will be processed and submitted for genomic characterization using the established NCI Genome Characterization Pipeline. Subsequent genomic and clinical data will be hosted at the NCI Genomic Data Commons (GDC).

  Study phs002253

• Single-Cell Genome Sequencing of Gastrointestinal Carcinomas

  We experimentally derived copy number profiles and transcriptome profiles of gastrointestinal cancers using single cell sequencing. Using a microfluidic droplet partitioning system, we isolated individual cells of a suspension from a primary solid tumor into droplets. These droplets tag the resultant genomic or transcriptomic material with an identifying barcode that enables bioinformatic single cell tracking. From this joint analysis, we determined the overall level of genomic instability for gastrointestinal cancers as well as transcriptomic consequences from these events.

  Study phs001711

• Pharmacogenomics of Rheumatoid Arthritis Therapy

  Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis worldwide and affects 1.3 million adults in the USA. It has previously been studied using phenotype algorithms to identify electronic health records (EHR) case cohorts. Early genetic studies of EHR-linked cohorts of RA patients have been replicated in known associations. Further development of collections of EHR-linked cohorts for RA and other phenotypes may enable not only enhanced understanding of disease risks but also the investigation of outcomes and treatment responses.

  Study phs000983

• High-throughput determination of the antigen specificities of T cell receptors in single cells

  High-throughput linking of T cell receptor (TCR) sequences to their binding antigens is vital for immune profiling, yet challenging. We present Tetramer associated TCR Sequencing (TetTCR-Seq) to address this challenge. Binding is determined using a library of DNA-barcoded antigen tetramers that are rapidly and inexpensively generated using an in vitro transcription/translation platform. We included CMV+ donors (CMV seropositive donors who are infected with Cytomegalovirus) to screen for CMV specific TCRs.

  Study phs001678

• Longitudinal Assessment of Methylmercury and Gut Microbes During Pregnancy

  Methylmercury is a potent neurotoxin, and the fetal period is the most vulnerable exposure period. There is significant variability in methylmercury metabolism, which has been attributed to differences in the structure and function of the gut microbiome. Our main objective was to better understand the interplay between gut microorganisms and methylmercury metabolism during pregnancy. To address this aim, associations were investigated between maternal biomarkers (blood, hair, stool) for prenatal methylmercury exposure and maternal gut microbiota during early and late gestation.

  Study phs001768

• The Genetics of Lung Cancer Susceptibility in Smokers

  Over 85% of all patients diagnosed with lung cancer report a history of tobacco use, though only 10% of tobacco smokers eventually develop lung cancer. Epidemiologic studies have shown that family members of patients with lung cancer have a higher risk of developing lung cancer than controls. In an effort to identify variants associated with tobacco induced lung cancer, we have sequenced germline DNA from affected and unaffected members of families with strong histories of tobacco related lung cancer.

  Study phs000728

• Evolution of Chronic Lymphocytic Leukemia to Richter's Syndrome (RS)

  Richter's syndrome arising from chronic lymphocytic leukemia is a striking example of an aggressive malignant histology that emerges from indolent cancer. To understand this process, we reconstructed phylogenies based on whole exome sequencing of matched normal, CLL and RS samples. We computationally deconvoluted CLL and RS clones and identified drivers of transformation. We additionally performed whole genome sequencing, whole transcriptome sequencing and single-cell transcriptome sequencing to understand the mutational signatures, genome-wide events and gene expression changes associated with transformation.

  Study phs002458

• Genomic and Transcriptomic Sequencing of CAR-T-Treated Patients

  Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized the treatment of hematologic malignancies. Approximately half of patients with refractory large B-cell lymphomas achieve durable responses from CD19-targeting CAR-T treatment; however, failure mechanisms are identified in only a fraction of cases. Here we use next-generation sequencing technologies to characterize the genomic and transcriptomic features of CAR-T cells and tumors that influence therapeutic responses. Please see our submission to NCBI GEO (GSE273170) for additional data.

  Study phs002922

• Transcriptome HCCO Hypoxia and Doxorubicin resistance

  We hypothesized that HCCO-intrinsic determinants of response to hypoxia or doxorubicin could be reflected in the gene expression profiles of the HCCOs. Therefore, we selected for comparative transcriptomic analysis two sets of 4 HCCO lines that were severely (hypoxia-sensitive) or barely affected (hypoxia-resistant) by hypoxia in an ATP-based proliferation assay or two sets of 4 HCCO lines whose doxorubicin response curves were clearly separated both under normoxic and hypoxic culture conditions for comparative transcriptomic analysis.

  Study EGAS50000000042