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

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• Profiles of Extracellular RNA in Cerebrospinal Fluid and Plasma from Subarachnoid Hemorrhage Patients

  Brain injury resulting from hemorrhagic stroke is clinically challenging to manage and results in high rates of morbidity and mortality. The pathophysiology of brain damage resulting from aneurysmal subarachnoid hemorrhage (aSAH) is largely unknown, and methods to treat and monitor patients are variable with no meaningful correlations to patient outcome. Prediction of patient risk for serious neurological complications is currently a significant clinical obstacle. An extracellular RNA (exRNA) biomarker to predict onset and severity of brain damage would improve patient outcomes. We sequenced plasma and CSF samples from adult patients with SAH. Samples were collected from post bleed day 1 to day 7. Total exRNA was isolated from each sample. In addition, we prepared a subset of 140 CSF samples, isolating the RNA contained within extracellular vesicles and vesicle-depleted biofluid.

  Study phs001759

• National Human Genome Research Institute Tumor Sequencing Project (TSP) - Lung Adenocarcinoma

  The Tumor Sequencing Project (TSP) Consortium is a collaboration among participants at the Baylor College of Medicine Human Genome Sequencing Center, the Broad Institute Genome Sequencing Platform, the Dana Farber Cancer Institute, the Memorial Sloan-Kettering Cancer Center, the Genome Sequencing Center and Siteman Cancer Center at Washington University, the M.D. Anderson Cancer Center and the University of Michigan Medical Center. The TSP Part A will pilot approaches to large-scale identification of genomic changes in tumors by sequencing the exonic regions of 623 genes in 188 specimens of adenocarcinoma of the lung, as well as using high density SNP genotyping arrays for high resolution identification of changes in chromosomal copy number. The TSP Part B will pilot approaches to tumor characterization of lung adenocarcinoma samples using next-generation sequencing technologies and benchmark those results against Part A data generated with ABI3730 instruments.

  Study phs000144

• RNAseq Transcriptomic Analyses of European Ancestry Samples in MGS Dataset

  Schizophrenia is a common and severe psychotic disorder. While some common SNPs and rare copy number variants have been identified as being significantly associated with disease risk, the biological mechanisms remain undefined. To identify gene expression abnormalities in schizophrenia, we generated whole-genome gene expression profiles using RNAseq on lymphoblastoid cell lines from schizophrenia cases and controls of European ancestry. Subsets of these data have been used in three studies: (1) gene expression outliers (extreme tails of the distribution of transcript expression values) in 634 cases and 713 controls (PMID: 26022996); (2) baseline differential gene expression by affection status in 529 cases and 660 controls (PMID: 28418402); and (3) baseline versus dopamine stimulated differential gene expression by affection status in 514 cases and 690 controls (PMID: 30115913). Various classes of classes were enriched in the differentially expressed genes, especially brain expressed genes and genes related to immune processes.

  Study phs001932

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): Digital Health Solutions for COVID-19: COVID Community Action and Research Engagement (COVID-CARE)

  Vibrent Health will expand the Vibrent Digital Health Solutions Platform (DHSP) implementation to additional populations among diverse user groups for additional validation of the technology's performance, usability, and reliability in refinement of analytics generating predictive algorithms for infection and that support individual, organizational, community and societal-level decision-making in the COVID-19 pandemic response. This includes the aims to innovate a technology that can differentiate between COVID-19 and flu (or other respiratory illness); develop and test a novel WIFI-based contact tracing tool using a University’s enterprise WIFI system and software release of augmented contact tracing capabilities in Vibrent's DHSP; and develop a full technical integration approach and strategy to support data exchange between this solution and the NCI data hub.DOI: https://rapids.ll.mit.edu/10.57895/ravs-1b57

  Study phs002533

• Comparative Sequence Analysis Between Primary and Metastatic Colorectal Cancer Lesions

  Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease. Further, the identification of discordant mutations between matched primary and metastatic tumors would be of biological interest for the delineation of biomarkers of tumor progression and metastasis. To explore the degree of genetic heterogeneity between matched primary and metastatic tumors in CRC, we performed whole genome sequencing of four patient "trios" comprised of a primary colon tumor, a liver metastasis, and matched normal (non-cancerous) tissue. Somatic mutations and indels were called in each tumor and compared between primary and metastatic lesions.

  Study phs000790

• Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing

  Adapted from manuscript in review: Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC) but there have been few whole genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. These include highly recurrent tandem duplications involving an upstream enhancer of AR. A subset of cases also displayed a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC nominate new alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the noncoding mCRPC genome remain to be discovered.

  Study phs001577

• Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver

  Highly metabolic liver is exposed to many sources of spontaneous mutagenesis resulting in increased genome instability that, potentially, causes age-related functional liver failure. Here we comparatively characterize the somatic mutational landscape in single human liver cells from individuals of various ages. Mutation frequency is very high in normal human hepatocytes, increasing dramatically with age as compared to other tissues and cell types, e.g., B-cells, neurons, and clonal surrogates of various adult stem cells. Moreover, differentiated hepatocytes tend to accumulate more mutations compared to age-matched proliferating liver stem cells (LSCs). Mutation spectra also differ dramatically between different cell types. Elevated oxidative hallmarks are observed in mouse liver and ex vivo cultured LSCs, but not during liver aging. Overall, human liver is prone to high age-dependent genome instability, compared to other tissues, and reveals functional difference between LSCs and hepatocytes.

  Study phs001956

• CRISPR-Mediated ASD Gene Knockout Reduces Neuronal Activity

  Autism Spectrum Disorder is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction of iPSCs allowed production of excitatory neurons, and mutant proteins were not detectable. RNAseq revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory post-synaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2- and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.

  Study phs001816

• Modeling Malignant Progression in Glioma

  Gliomas are the most common primary brain tumor in humans. Low-grade gliomas (WHO grade II) invariably progress to high-grade gliomas (WHO grade III or IV). Although malignant progression may take many years, the survival rate after transformation to a high-grade glioma is poor, often only 12-15 months. In this data set, we have identified low-grade gliomas that have progressed to high-grade gliomas or high-grade gliomas that have progressed from low-grade gliomas. Some cases are matched pairs (meaning we have both the original low-grade tumor and the subsequent high-grade tumor). The samples deposited have been analyzed with bulk-RNA sequencing. They are also de-identified but are clinically annotated. When available, genetic information including IDH mutation status, 1p/19q deletion and histological subtype are also included.

  Study phs002607

• Validation of Gene Array to Predict Bacterial Co-infection In Adults Hospitalized with Viral Lower Respiratory Tract Infections (LRTI)

  Accurate tests for microbiologic diagnosis of lower respiratory tract infections (LRTI) are needed. Gene expression profiling of whole blood represents a powerful new approach for analysis of the host response during respiratory infection that can be used to supplement pathogen detection testing. Using qPCR, we prospectively validated the differential expression of 10 genes previously shown to discriminate bacterial and non-bacterial LRTI confirming the utility of this approach. In addition, a novel approach using RNAseq analysis identified 141 genes differentially expressed in LRTI subjects with bacterial infection. Using "pathway-informed" dimension reduction, we identified a novel 11 gene set (selected from lymphocyte, α-linoleic acid metabolism, and IGF regulation pathways) and demonstrated a predictive accuracy for bacterial LRTI (nested CV-AUC=0.87). RNAseq represents a new and an unbiased tool to evaluate host gene expression for the diagnosis of LRTI.

  Study phs001248