14313 results for ""Pennsylvania+German"+ACS+study+'Socius'+open+access"

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• Translating Gene-Calcium Interactions to Precision Medicine for Colorectal Cancer

  Identify functional and rare SNPs and their interactions with Ca intake levels in relation to risk of incident adenoma using whole-exome resequencing of 2468 colorectal adenoma cases and controls from PLCO. We will genotype promising rare and functional SNPs associated with incident adenoma in 570 incident cancer cases, 1,710 healthy controls, 710 adenoma recurrence cases and 966 recurrent adenoma controls from the intervention arm of PLCO to both confirm the associations with adenoma, and to identify when, in the natural history of CRC, chemoprevention by Ca-gene interactions occurs. We hypothesize that Ca-gene interactions prevent early-stage (incident adenoma) and mid-stage (adenoma recurrence) carcinogenesis as well as span the entire CRC carcinogenesis spectrum (i.e. incident CRC).

  Study phs002164

• NPC Genome Project

  Niemann-Pick disease, type C1 (NPC1) is neurodegenerative disorder due to pathological variants of NPC1. NPC1 is predominately a pediatric/adolescent disorder, although adult onset cases have been described. The NPC1 protein functions to move unesterified cholesterol from the endolysosomal lumen to make it bioavailable for cellular function. Impaired NPC1 function results in endolysosomal accumulation of unesterified cholesterol and other lipids. The NPC1 phenotype is extremely heterogeneous, both with respect to age of onset and sign/symptom complex. Comparison of individuals homozygous for the common p.I1061T variant and affected siblings suggests that other genes can significantly modify the clinical phenotype. The goal of this project is to obtain genome sequencing on ~200 individuals with NPC1 in order to facilitate identifying potential genetic modifiers.

  Study phs003214

• HuBMAP: A 3-D Tissue Map of the Human Lymphatic System

  The major goal of the 3-D Tissue Map of the Human Lymphatic System is to use microscopic and biomolecular procedures to facilitate co-registration pipelines and common 3D reconstruction algorithms. Tissue collected from human spleen, thymus and lymph node will be spatially resolved at the single cell level both within and across individuals. The approach employed involves sequencing of transcriptomes of dissociated cells and mapping to histological sections using CO-Detection by indEXing (CODEX) and /or Imaging mass spectroscopy, two highly multiplexed methods employing antibody-tagged target epitopes. Additionally, light sheet fluorescent microscopy is used to provide a higher level context for structural localization on a larger volume. The molecular data provided by this project is obtained through single-cell RNA-seq.

  Study phs002268

• Tracing tumor evolution and heterogeneity of pleomorphic carcinoma of the lung

  Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous non-small-cell lung carcinoma whose underlying biology is still poorly understood. Forty-two tumor areas including 39 primary tumors and 3 metastases from 20 PPC patients were microdissected and the histologically distinct components were subjected to whole exome sequencing (WES) separately. Twenty non-tumor areas from matched PPC patients were also subjected to WES. Twist Human Core Exome + RefSeq + Mito-Panel kit (Twist Bioscience) was used for the whole exome capturing according to manufacturer’s guidelines. Paired-end 100-bp reads were generated on the Illumina NovaSeq 6000. After the sequencing, reads were aligned against the reference human genome GRCh38 using Burrows-Wheeler Aligner (BWA, v0.7.12)

  Study EGAS50000000314

• Capmatinib shows superior efficacy for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy

  Pediatric high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGGs, and are associated with devastating morbidity and mortality. To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion iHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy (RT).

  Study EGAS50000000137

• NGS-based monitoring of the T cell receptor repertoire in living donor kidney transplant patients undergoing combination cell therapy

  Tolerance induction through mixed chimerism is a promising approach to achieve long term graft patency without or only low dose maintenance immunosuppression. In this phase I/IIa academic trial kidney transplant recipients in the case group were co-transplanted with bone marrow from the same donor and received an autologous cell product. The control group did not receive donor bone marrow or an autologous cell product. Peripheral blood mononuclear cells were collected at multiple timepoints before and after transplantation and the recipients native T-cell receptor (TCR) repertoire at time points 0, 1, 3 and 6 months after transplantation as well as their donor reactive TCR repertoire were analysed using NGS-based TCR sequencing.

  Study EGAS50000000210

• BPH Tissues for Cell Culture and Analysis - A Patient-Derived Xenograft Model Using Benign Prostatic Tissues

  Our goal was to establish and characterize a patient-derived xenograft model for benign prostatic hyperplasia (BPH) using human benign prostatic tissues. Characterization of the model was done by histology, immunohistochemistry, proteomics, and transcriptome analysis (RNAseq). The RNAseq data will be deposited in dbGaP. Subjects were undergoing prostatectomy for prostate or bladder cancer, with concurrent BPH, and consented to the use of surplus tissue for research studies. The RNAseq studies included 6 patients. Phenotypic data include patient age, sex, prostate size, serum prostate-specific antigen (PSA) level, and international prostate symptom score (IPSS). Sequencing was done on an Illumina NovaSeq 6000, and data were analyzed using Kallisto. Data are submitted as raw sequencing (fastq) files.

  Study phs003692

• DAC for Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

  Ovarian cancer is a leading cause of death from gynecological malignancies worldwide. No effective screening methods exist resulting in tumor detection at advanced stages where treatment is less effective. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women, mostly post-menopausal, from the European Union or the United States with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model that incorporated multi-analyte fragmentome data and protein measurements, we evaluated the detection of ovarian cancer in two clinical settings, detection of ovarian cancers among a healthy population, and classification of adnexal masses as benign or malignant. The combined approach detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I–IV, respectively (AUC=0.96, 95% CI: 0.94-0.99), including 90% of high grade serous ovarian cancers. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I–IV (p=0.001, two-sided test of equal proportions). Additionally, our approach differentiated benign masses from ovarian cancers with high accuracy (AUC of 0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

  Dac EGAC50000000332

• Transcriptome analysis of human longitudinal whole blood samples from PCR-positive and PCR-negative adults following controlled inoculation with Influenza A (H3N2) virus.

  Transcriptome analysis of influenza A (H3N2) human challenge samples. Understanding of the transcriptomic profile of individuals in early influenza infection is limited. To investigate this, longitudinal whole-blood samples (n=178) were taken from adult participants following controlled inoculation with Influenza A H3N2 virus (sampling at baseline (0) and days 1, 2, 3, 7, 10 and 14 post-challenge). Most participants became influenza PCR-positive; a minority remained PCR-negative. Total RNA was extracted from PAXgene tubes before undergoing globin and rRNA depletion. DNA libraries were constructed using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina. All samples were then sequenced using Illumina NovaSeq 6000.

  Study EGAS50000000679

• AYA glioma NGS

  Gliomas are a major cause of cancer-related death in adolescents and young adults (AYA, ages 15-39 years). Different molecular alterations drive gliomas in children and adults leading to distinct biology and clinical consequences. At the convergence of these age groups - the AYA population – little is known about the implications of pediatric vs adult-type alterations. To address this, we analyzed a population-based cohort of 1456 clinically and molecularly characterized gliomas aged 0-39 years. Potentially targetable pediatric-type alterations were found in 31% of AYA gliomas and conferred superior outcomes compared to adult-type alterations. This submission includes the generated NGS data for children, adolescent, and young adults with gliomas. Data includes targeted panel of glioma genes and low-pass WGS (1x coverage).

  Study EGAS50000000383