14347 results for ""Pennsylvania+German"+ACS+study+'Socius'+open+access"

in 21.22 milliseconds.

• Ex vivo RNA-seq in moderate COVID-19 monocytes

  This dataset was used to compare gene expression profiles of ex vivo isolated classical CD14+ monocytes from patients with moderate COVID-19 to those of healthy individuals. Blood samples were taken from patients with moderate COVID-19 admitted to hospitals in London (Hammersmith Hospital, Charing Cross Hospital, Saint Mary’s Hospital) 3-14 days after disease onset and 0-2 days after hospitalization and positive PCR, and before study treatment initiation. Moderate patients displayed mild or moderate COVID-19 pneumonia, defined as grade 3 or 4 WHO severity. Samples were collected from March 2020 to February 2021. Healthy donors were Imperial College staff with no prior diagnosis of or recent symptoms consistent with COVID-19, and where possible, were matched in age and sex distribution with COVID-19 patients. None of the participants of this study were COVID-19 vaccinated. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll Hypaque (GE Healthcare) gradient centrifugation <4 hours after blood collection. CD14+ monocytes were isolated using a positive selection magnetic sorting kit (StemCell Technologies, UK) from total PBMC and stimulated with vehicle, UV-inactivated SARS-CoV-2 (CoV-2). RNA was isolated using the RNeasy Micro Plus Kit (QIAGEN) following the manufacturer’s guidelines. RNA-sequencing was performed by the Oxford Genomics Centre. PolyA-enriched strand- specific libraries were prepared using NEBNext Ultra II Directional RNA Library Prep Kits (Illumina). All samples were pooled together and 150bp PE reads were sequenced on a Novaseq 6000 system.

  Dataset EGAD00001009800

• Samples linked to the study "Performance comparison of three DNA extraction kits on human whole-exome data from formalin-fixed paraffin-embedded normal and tumor samples"

  We generated 42 human whole-exome sequencing data sets from fresh-frozen (FF) and FFPE samples. These samples include normal and tumor tissues from two different organs (liver and colon), that we extracted with three different FFPE extraction kits (QIAamp DNA FFPE Tissue kit and GeneRead DNA FFPE kit from Qiagen, Maxwell\textsuperscript{TM} RSC DNA FFPE Kit from Promega). Variant calling analysis shows a very high rate of concordance between matched FF / FFPE pairs and equivalent performance for the three kits we analyzed. We find a significant variation in the difference of total number of variants called between FF and FFPE samples for the three different FFPE DNA extraction kits. Coverage analysis shows that FFPE samples have less good indicators than FF samples, yet the coverage quality remains above accepted thresholds. We detect limited but significant variations in coverage indicator values between the three FFPE extraction kits. Globally, the GeneRead and QIAamp kits have better variant calling and coverage indicators than the Maxwell kit on the samples used in this study, although this kit performs better on some indicators and has advantages in terms of practical usage. Taken together, our results confirm the potential of FFPE samples analysis for clinical genomic studies, but also indicate that the choice of a FFPE DNA extraction kit should be done with careful testing and analysis beforehand in order to maximize the accuracy of the results.

  Dataset EGAD00001004066

• Transcriptome human nasal epithelium

  1. Odors are detected, firstly, by olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose. This neurons then project directly to the olfactory bulb in the brain. Olfaction depends on cellular regeneration of the OE, olfactory bulb and hippocampus, and on their continual re-wiring. The olfactory neural pathway includes regions of the frontal, temporal and limbic brain, which in turn overlap with brain areas involved in brain disorders. OSNs are the only aspect of the human brain exposed to the external environment. This not only makes them vulnerable to environmental changes, but also accessible for biomedical studies. We have already sequenced and developed a protocol for analyzing the transcriptome of mouse main olfactory epithelium and single OSNs. We propose here to perform a similar study for samples from the human olfactory epithelium. We have developed a minimally invasive method for obtaining human OSNs, among other cells from the nasal epithelium. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We would like to further characterize them by RNA sequencing. This will give us valuable insight into human olfaction. It will also provide a first step into a new avenue to study, and find biomarkers for, brain diseases though the analysis of these easily available neurons. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002226

• Cincinnati Children's Hospital Medical Center (CCHMC) - eMERGE Phase IIIA Data

  This submission includes genotyping or sequencing data from separate cohorts, each is described in separate paragraphs below. Extreme early onset obesity Obesity is a serious epidemic condition and on the rise in the United States. Today, nearly one out of three children is overweight or obese in this country. According to the Center for Disease Control, 35.7% of American adults and 17% of American children are obese. The medical costs associated with obesity are estimated to be in the billions. Without a doubt, interplay of additive genetic effects and common environmental effects influence this complex disease. However, despite being exposed to so-called "obesogenic environment", a large proportion of the population remains of normal weight. These observations suggest that innate, non-environmental, factors make some individuals more susceptible to obesity providing support for biological mechanisms, and thus genetic factors, to underlie the individual's response to the obesogenic environment. In young children with severe obesity the relative role of genetics and in utero programming are likely to outweigh the short duration of environmental and lifestyle exposures. This group is therefore an ideal one to study as they are likely enriched for variants that influence the risk of developing obesity. The purpose of this project is to further study and understand obesity in childhood and to develop a repository of samples for future studies into obesity. Eosinophilic Esophagitis (EoE) Eosinophilic Esophagitis (EoE) is one of the manifestations of eosinophilic gastrointestinal inflammation which have profound effects on a patient's health and development. Results of epidemiologic studies performed through our center demonstrate that eosinophil-associated gastrointestinal disease is not an uncommon entity. While the epidemiology of eosinophilic esophagitis has not been thoroughly studied until recently, there appears to be a significant increase in the diagnosis of EoE in the last decade. Based on our research, this mainly reflects increased disease recognition, but there is also a bona-fide increase in disease incidence which coincides with the increasing incidence of asthma and allergic diseases in the industrialized world. In addition, many patients with intractable symptoms thought in the past to represent atypical GERD or other disorders are now being recognized as having EoE. Diagnosis of EoE requires endoscopy and biopsies to document the characteristic histologic findings of esophageal eosinophilia. In general, this study proposed to elucidate the mechanisms underlying eosinophil growth, survival, migration, and function, and to investigate and further characterize the pathophysiology of, clinical manifestations of, and spectrum of disease severity of eosinophilic esophagitis in humans. The de-identified genotyping and genome wide association data generated as part of this research will be used for further genome research. Familial Sample Repository (FSR) and Directed Sample Repository (DSR) De novo mutations could cause many diseases, which has been demonstrated in mental retardation, autism and many rare genetic disorders. Family-based studies have a variety of advantages over case/control studies, including the elimination of analysis artifacts related to population stratification, the detection of genes that act through a recessive mechanism of inheritance and validation that the trait is not transmitted from a parent, something not possible using a case/control design. Additionally, DNA from families can be used to identify de novo mutations suggesting strong candidate causal polymorphisms. For this project, samples will be collected from families on an on-going basis. Families may be recruited because the patient either has a disease which is thought to be of genetic origin or from the general patient population to serve as controls or future identified diseases. Some phenotypes under study include fibroblastic rheumatism, diaphragmatic hernia, polymicrogyria, severe congenital neutropenia, primary sclerosing cholangitis and staph infection. CLRR-Cincinnati Lupus Registry and Repository Systemic lupus erythematosus (SLE) is a complex, partially understood autoimmune disorder. Genetic origins for SLE are supported by high heritability (> 66%), familial aggregation, increased monozygotic twin concordance, genetic linkages, and candidate gene genetic association, including HLA genes, Fc receptors, and complement components. Relevant environmental factors likely include infections (Epstein-Barr virus), therapeutics, personal habits (smoking), and diet. To continue a research resource facility for collection of well-characterized pedigrees containing a proband with systemic lupus erythematosus we develop this repository. Juvenile Idiopathic Arthritis (JIA) Juvenile Idiopathic Arthritis (JIA) is a debilitating complex genetic disorder characterized by inflammation of the joints and other tissues and shares histopathological features with other autoimmune diseases. It is considered complex genetic traits. There are more than 50,000 children with JIA in the USA, approximately 1 per 1000 births, which is about the same incidence as juvenile diabetes. It is believed that genes in the major histocompatibility complex (MHC) play a role in defining genetic risk, and it can be hypothesized that loci in other chromosomal regions are involved in conferring risk in JIA. These candidate chromosomal regions can be identified using genome-wide association analyses. The long-term goal is a comprehensive understanding of the genetic basis of these disabling arthropathies for which the molecular basis is not presently understood. These data will contribute to a national resource for the study of autoimmunity in children. Better Outcomes for Children-Cytogenetics Since 2007, more than 4000 samples, enriched with various rare or common genetic diseases as well as specific chromosomal abnormalities such as deletions and duplications have been genotyped for the purpose of subsequent GWAS and Phewas analyses and uncovering main genetic effects.

  Study phs001011

• First genome-wide association study in an Australian Aboriginal population provides insights into genetic risk factors for Body Mass Index and Type 2 Diabetes

  A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians. To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,355,133 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community. Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs. No associations achieved genome-wide significance, commonly accepted as P<5x10-8. Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia >45,000 years ago. The top hit (rs10868204 Pgenotyped=1.50x10-6; rs11140653 Pimputed_1000G=2.90x10-7) for BMI lies 5’ of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R). PIK3C2G (rs12816270 Pgenotyped=8.06x10-6; rs10841048 Pimputed_1000G=6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped=4.65x10-5; rs13225016 Pimputed_1000G=6.57x10-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 Pgenotyped=5.59x10-6, Pimputed_1000G=5.73x10-6) for T2D lies 5’ of BCL9 that, along with TCFL2, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway. Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions. Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped=4.49x10-4) for BMI and IGF2BP2 Pimputed_1000G=2.55x10-6) for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.

  Study EGAS00001001004

• The University of Hong Kong Colon Cancer GCV Study

  Background: Ganciclovir (GCV) is widely used in solid organ and hematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. Methods: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. Results: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig¬¬ were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV¬sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. Conclusions: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

  Study EGAS00001006707

• Molecular features of adenomas predicting metachronous colorectal cancer: a nested-case control study

  "Background & Aims: Current morphological features defining advanced adenomas (size ≥10 mm, high grade dysplasia or >25% villous component) cannot optimally distinguish individuals at high-risk or low-risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy number alterations are associated with adenoma-to-carcinoma progression (cancer-associated events; CAEs). We aimed to evaluate whether CAEs can better predict an individual’s risk of me-CRC than the morphological advanced adenoma features. Methods: In this nested case-control study, 529 individuals with a single adenoma at their first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy number profiles were determined, by means of low-coverage whole genome sequencing. We assessed the prevalence of CAEs in advanced and non-advanced adenomas and its association with me-CRC. For the latter, cases (with CRC) were matched to controls (without CRC), with the same follow-up period as cases, as well as age and sex. Subsequently, odds ratios (OR) for the association of the presence of an advanced adenoma or a molecularly-defined high-risk adenoma with me-CRC were calculated. Results: Molecular high-risk features were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. Me-CRC was more strongly associated with advanced adenomas (OR 3.58; 95% CI 2.27-5.72) than with molecular high-risk adenomas (OR 1.90; 95% CI 1.14–3.16). After adjusting for other variables, only advanced adenoma remained significantly associated with me-CRC (OR 3.39; 95% CI 2.10–5.55). Conclusion: Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. " Project goal: Evaluate the value of DNA copy numbers alterations detected in a baseline adenoma, in the prediction of risk of metachronous CRC

  Study EGAS00001007039

• Kaposi_sarcoma_exome

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Kaposi sarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000032

• _WGS__Somatic_mutation_in_skin_epidermis__SMS_

  Previously we have sequenced 2mm2 biospies of human epithelia at high depth using a custom bait set. This has identified a range of mutations. Some of the biospies are predicted to be clonal and we would like to perform WGS to give an insight into mutational burden, and CNV which may be associated with these mutations.

  Study EGAS00001004464

• A common single nucleotide variant in T is strongly associated with chordoma

  Chordoma is a rare malignant bone tumor that expresses the transcription factor T. We conducted an association study of 40 patients with chordoma and 358 ancestry-matched, unaffected individuals with replication in an independent cohort. Whole-exome and Sanger sequencing of T exons reveals a strong risk association ( allelic odds ratio (OR) = 4.9, P = 3.3x10-11, CI= 2.9-8.1) with the common (minor allelic frequency >5%) non-synonymous SNP rs2305089 in chordoma, which is exceptional in cancer genetics.

  Dataset EGAD00001000226