12444 results for "cancer studies using rna-seq"

in 40.15 milliseconds.

• NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Asthma): Genetic variants affecting susceptibility and severity

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The exome sequencing asthma project includes 200 African-Americans with asthma from the NHLBI multicenter Severe Asthma Research Program (SARP). SARP participants were recruited at the NHLBI SARP sites with an emphasis on recruiting severe asthmatics (Moore et al., Am J Respir Crit Care Med, 2010. PMID: 19892860). Asthma status was based on both a physician's diagnosis and either bronchodilator reversibility or hyper-responsiveness to methacholine as well as less than 5 pack years of smoking. All subjects were carefully characterized using the standardized SARP protocol which included spirometry (medication withheld), maximum bronchodilator reversibility, hyper-responsiveness to methacholine (not performed in subjects with low baseline FEV1), skin-tests to common allergens, questionnaires on health care utilization and medication use and sputum, lung imaging and bronchoscopy in a subset. In addition GWAS data are available (phs000355, Illumina platform).

  Study phs000422

• PAGE: Global Reference Panel

  Stanford contributed samples to the PAGE study that can act as a population reference dataset across the globe. Therefore this dataset includes reference individuals, without phenotypes, chosen to help infer ancestry that will help us understand the diverse samples available in PAGE. The complete dataset comprises individuals of European, African, Asian, Oceanian, and Native American descent, from a total of over 50 populations. A subset of these individuals from Puno, Peru and Easter Island (Rapa Nui), Chile, are included in the PAGE samples that were whole genome sequenced in 2015. Additional details are available in the Study Acknowledgments. The Global Reference Panel comprises 6 sample sets: A population sample of Andean individuals primarily of Quechuan/Aymaran ancestry from Puno, Peru A population sample of Easter Island (Rapa Nui), Chile Individuals of indigenous origin from Oaxaca, Mexico Individuals of indigenous origin from Honduras Individuals of indigenous origin from Colombia Individuals of indigenous origin from the Nama and Khomani KhoeSan populations of the Northern Cape, South Africa In addition, we genotyped publicly available samples that will be hosted on the Bustamante lab website (https://bustamantelab.stanford.edu/). These comprise large public datasets to provide an open reference dataset for the world: The additional related individuals from the Americas in the Human Genome Diversity Panel (H952) plus all additional samples from the Americas A subset of the unrelated individuals from the Maasai in Kinyawa, Kenya (MKK) dataset from the International Hapmap Project hosted at Coriell Additional samples will be available for restricted use with a data access agreement with the Bustamante Lab. This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (phs000356).

  Study phs001033

• Glial Cell Line-Derived Neurotrophic Factor (GDNF) Polymorphisms and Anxiety, Depression

  GDNF gene variants were studied as possible risk factors of depression or anxiety on a young sample. The association study involved eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide polymorphisms and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no psychiatric history. Results provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p=0.00070 and p=0.00138 for rs3812047 and rs3096140, respectively). Haplotype analysis confirmed the role of these SNPs (p=0.00029). A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. This is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140) and individual variability of anxiety using self-report data from a non-clinical sample. Reprinted from Kotyuk et. al., 2013 (Kotyuk, E., Keszler, G., Nemeth, N., Ronai, Z., Sasvari-Szekely, M., and Szekely, A. (2013). Glial Cell Line-Derived Neurotrophic Factor (GDNF) as a Novel Candidate Gene of Anxiety. PLoS One,8, (12) PMID: 24324616), with permission from Publisher (All content of articles published in PLOS journals is open access. You can read about our open access license here: http://www.plos.org/about/open-access/. To summarize, this license allows you to download, reuse, reprint, modify, distribute, and/or copy articles or images in PLOS journals, so long as the original creators are credited (e.g., including the article's citation and/or the image credit); Laura Perry; Staff EO;PLOS ONE)

  Study phs000713

• Binding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic Mechanisms

  This study is focused on multiple sclerosis (MS). MS is likely caused by a combination of genetic and environmental factors; however, the mechanisms contributing to these factors remain poorly understood. Epstein-Barr virus (EBV) in particular is a well-established environmental risk factor for MS. We have created a computational algorithm that systematically searches for common molecular mechanisms that might be impacted at multiple MS-associated loci. Using this algorithm, we have discovered that over 40% of MS-associated loci contain MS genetic variants that fall within regions of the human genome occupied by the EBV-encoded EBNA2 protein. The same MS-associated variants also impact gene expression levels of MS-associated genes in EBV-infected B cell lines. Our hypothesis is that allele-dependent binding of EBNA2 and its co-factors explains the allele-dependent risk at many MS genetic loci. Importantly, this hypothesis links the genetic associations of MS to the known molecular roles played by EBV and Notch signaling in disease processes.Subjects with and without MS were recruited into an Institutional Review Board (IRB)-approved protocol through the Cincinnati Autoimmune Registry and Repository. From each subject, DNA from peripheral blood was isolated for whole genome sequencing (WGS). These data will be used to identify genotype-dependent transcriptional regulation in cells assessed from patients and controls. This WGS data was deposited before the full integration of sequence data with other functional genomic data types.From each subject, 90 mL of blood is drawn for isolation of peripheral blood mononuclear cells from which primary B and T cells will be isolated. For each B cell isolation, an EBV-transformed B cell line will be derived.

  Study phs003240

• Sudden Death in the Young Case Registry

  Knowledge gaps persist about the incidence of and risk factors for sudden death in the young (SDY). The SDY Case Registry is a collaborative effort between the National Institutes of Health, the Centers for Disease Control and Prevention, and the Michigan Public Health Institute. Its goals are to: (1) describe the incidence of SDY in the United States by using population-based surveillance: (2) compile data from SDY cases to create a resource of information and DNA samples for research; (3) encourage standardized approaches to investigation, autopsy, and categorization of SDY cases; (4) develop partnerships between local, state, and federal stakeholders toward a common goal of understanding and preventing SDY; and (5) support families who have lost loved ones to SDY by providing resources on bereavement and medical evaluation of surviving family members. Built on existing Child Death Review programs and as an expansion of the Sudden Unexpected Infant Death Case Registry, the SDY Case Registry achieves its goals by identifying SDY cases, providing guidance to medical examiners/coroners in conducting comprehensive autopsies, evaluating cases through child death review and an advanced review by clinical specialists, and classifying cases according to a standardized algorithm. The SDY Case Registry also includes a process to obtain informed consent from next-of-kin to save DNA for research, banking, and, in some cases, diagnostic genetic testing. The SDY Case Registry will provide valuable incidence data and will enhance understanding of the characteristics of SDY cases to inform the development of targeted prevention efforts. For cases where informed consent has been obtained for research genomic sequencing has been performed. On these cases genomic data, phenotype information and on a limited number of cases redacted autopsy reports will be available through dbGaP.

  Study phs003221

• Genetic Investigations of Attention-Deficit/Hyperactivity Disorder

  Design and Aims:We conducted whole-exome DNA sequencing on 152 parent-child trios (456 individuals total) that included a child meeting DSM-IV or DSM-5 criteria for ADHD along with both biological parents to identify rare de novo damaging DNA variants associated with ADHD risk. Mutation rates were compared between 147 ADHD trios and 780 unaffected control trios. We aimed to identify specific ADHD risk genes by combining the de novo trio data with rare variant data from an independent case-control cohort.Population Information:ADHD trios were collected from four sites. The 780 control trios were unaffected siblings from the Simons Simplex Collection who scored in the normal range on the Child Behavior Checklist (CBCL) or Adult Behavior Checklist (ABCL) ADHD subscale.Molecular Technologies:Whole-exome DNA sequencing was performed on the ADHD trios using the IDT xGen V1 or Agilent SureSelect All Exon V7 capture and the Illumina NovaSeq6000 sequencer. Control trios were previously sequenced with the NimbleGen SeqCap EzExomeV2 capture and Illumina HiSeq 2000 sequencer. Joint variant calling was performed for all trios. Rare de novo variants with allele frequency Principal Findings:We found a 1.67-fold enrichment of rare de novo damaging variants and a 1.93-fold enrichment of ultra-rare de novo damaging variants in ADHD cases vs controls. By integrating the de novo data with an independent case-control cohort, KDM5B was identified as a high-confidence ADHD risk gene (FDR=0.04). Three potential risk genes were also identified. Twenty-three genes with ultra-rare damaging de novo variants in ADHD overlapped with previously reported risk genes for other neuropsychiatric conditions. Exploratory analyses showed enrichment of these genes in early neurodevelopmental pathways.

  Study phs003647

• Regenerative effects of MSC treatment on busulfan-induced small intestine damaged organoids.

  Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Second-line available therapies are immunosuppressants or mesenchymal stromal/stem cell (MSC) infusions. Data from our institution and others demonstrate rescue of approximately 40-50% of patients suffering from aGvHD with mesenchymal stromal/stem cells (MSCs) and minor side effects. Although promising, the better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. Here, we developed a novel 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating EMT, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. Collectively, we demonstrate that our novel in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium.

  Study EGAS00001007432

• Toxigenic Clostridium perfringens isolated from at-risk pediatric inflammatory bowel disease patients

  With the goal of studying mucosal-associated bacteria and products detrimental to inflammatory bowel disease (IBD) patients, we directly cultured bacterial communities from mucosal biopsies and examined for detrimental traits. Focusing on red blood cell lysis, a virulence trait, communities from 5 of 9 patients exhibited hemolytic activity. Clostridium perfringens was isolated from each hemolytic community, and whole-genome sequencing confirmed presence of hemolytic toxins – alpha toxin in all 5 strains, perfringolysin O (PFO) in 4 strains, alveolysin in 2 strains – and absence of enterotoxins. In vitro cytotoxicity experiments demonstrated strain supernatants were toxic to various cell types located beneath the intestinal epithelial barrier, including endothelial, neuroblasts, and neutrophils, while impact on epithelial cells was less pronounced. These findings suggest C. perfringens may be damaging particularly when intestinal barrier integrity is compromised, such as in IBD patients. Further characterization using purified toxins and genetic insertion mutants confirmed PFO toxin was sufficient for cell toxicity. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion (DRG) neuron cells in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom. Strikingly, C. perfringens was detected in biopsies of 8 of 9 pediatric patients while not in all corresponding stool samples, and in other datasets, C. perfringens was in stool samples of IBD adults (18.7-27.1%) much more frequently versus healthy (5.1%). Our findings showcase C. perfringens may have an important pathogenic impact on IBD patients. Similar to Clostridioides difficile, routine monitoring of C. perfringens and PFO toxins in patients may be beneficial.

  Study EGAS50000000334

• Cell-Free DNA Genomic and Fragmentomic Features for Early Outcome Prediction in Diffuse Large B-Cell Lymphoma

  Purpose: Diffuse large B-cell lymphoma (DLBCL) patients need an accurate and early risk stratification strategy as prompt therapy escalation may improve outcome. Patients and methods: We evaluated cell free DNA (cfDNA) genomic and fragmentomic features in 190 patients with large B-cell lymphoma from more than 40 hospitals in the Benelux using Whole Genome Sequencing (WGS). We defined a new metric called ACT score (Aberrations, Contribution of short fragments, Terminal motif analyses) by combining four cfDNA signals and evaluated its performance to predict end-of-treatment (EOT) response and survival. Results: Individual cfDNA features and ACT score were altered per EOT response after one cycle of treatment (T1). The ACT score at T1 outperformed all individual cfDNA features in predicting EOT response (AUC = 0.74). Patients with a positive ACT score had an inferior outcome compared to ACT score negative patients [progression-free survival (PFS): HR 5.0 (95% CI 3.1-8.2), log-rank test, p < 0.0001) and overall survival (OS): HR 6.5 (95% CI 3.5-12.2), log-rank test, p < 0.0001]. The 2-year PFS in ACT score positive and negative patients were 29.8% and 78.1%, respectively. The prognostic value of the ACT score is independent of the International Prognostic Index and interim imaging. Conclusions: ACT score computed from a single plasma sample collected after one cycle of treatment can predict clinical outcome. This low-cost and easy-to-interpret test does not require tissue biopsies or a priori knowledge of mutations and has the potential to aid patient selection in interventional clinical trials and risk-adapted treatment strategies.

  Study EGAS50000000412

• Cylindromas_sun_protected_and_exposed

  The project aims to look at mutational signatures in a rare inherited skin tumour syndrome called CYLD cutaneous syndrome. These patients develop multiple skin tumours that are seen at sun exposed and sun protected sites. We plan to carry out WGS on carefully curated tumours from such patients. We then plan to analyse this data for mutational signatures, comparing this between sun exposed and sun protected sites.

  Study EGAS00001002521