21029 results for "fc 26 coins Buyfc26coins.com is EA Sports official for FC 26 coins The service is affordable and quick..JIZq"

in 23.35 milliseconds.

• NEI CIDR Methylation Profiling of Primary Open Angle Glaucoma in NEIGHBOR Samples

  This is a case-control study of Primary Open Angle Glaucoma (POAG). POAG is a progressive optic neuropathy that eventually leads to blindness. More than 30 million people worldwide have Primary Open Angle Glaucoma (POAG), of which greater than 3 million are blind. Gene expression changes in the retina have been observed for POAG. Several recent studies, including the NEIGHBOR consortium (NEI Glaucoma Human genetic collaboration) have used GWAS to identify correlative regions of the genome. Despite this, the genetic basis of Glaucoma is not well understood. Epigenetic variation may account for low heritability and environmental effects on human disease. Despite the significant advances being made in understanding the role of epigenetics in gene regulation in other fields, little is known about the relationship between DNA methylation patterns, retinal gene expression, and retinal disease. The goal of this study is to identify differentially methylated regions in the peripheral blood of patients with POAG. The case identification is as per the NEIGHBOR description: Cases and controls were recruited from ophthalmology clinics and were examined by ophthalmologists. For cases the clinical exam included intraocular pressure measurements, optic nerve assessment and visual field evaluation. Controls had no family history of glaucoma, normal intraocular pressure and normal optic nerves. POAG and control samples come from two sources: Duke University and Massachusetts Eye and Ear Infirmary (MEEI). These samples were collected and genotyped as part of the NEIGHBOR study. From the 219 POAG cases contributed to NEIGHBOR by Duke, 75 samples were selected for exome sequencing by Dr. Terry Gaasterland (UCSD) as part of an ARRA grant. These samples were selected to mirror the distribution of the entire set of Duke patients for variables such as age, cup-to-disc ratio, CCT, and IOP. From these 75 patients, 43 were selected for our study and an additional seven patients chosen at random, for a total 50 patients from Duke. From the 219 Duke controls, 50 were selected to match the age (at the time of blood draw) and sex of the 50 Duke POAG patients. From the NEIGHBOR control samples from MEEI, 27 were selected who best matched the age (at blood draw), time since sample collection and sex of the POAG probands from GLAUGEN. Additional individual-level phenotype and genotype data may be obtained through the authorized access portal of phs000238 (Neighbor - Glaucoma GWAS Study).

  Study phs000458

• The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge

  Tumors are composed of many different cell types, ranging from the normal tissue micro-environment, infiltrating immune cells and tumour cells. This group of tumour cells is itself intrinsically highly heterogeneous, driven by the rapid mutation rate of cancer cells to become a mixture of different sub-populations. These different types of cells, called subclones, have different sets of mutations in their DNA. Because some subclones evolve from others, many subclones share mutations. While it is increasingly easy to determine what mutations are present in the tumor, it remains very difficult to determine which subclones have which mutations. The task of assigning mutations to subclones is called subclonal reconstruction.The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge (SMC-Het) is an international effort to improve standard methods for subclonal reconstruction: to quantify and genotype each individual cell population present within a tumor. The goal of this challenge is to identify the best subclonal reconstruction algorithms and to identify the conditions that affect their performance.

  Study EGAS00001002092

• Amplicon sequencing of duodenal adenoma

  The aim of this study is to analyze the methylation and mutation status of non-ampullary duodenal lesions in order to detect the genetic changes for predicting the progression to adenocarcinomas.

  Study JGAS000352

• The Southern African Human Genome Programme

  The Southern African Human Genome Programme (SAHGP) is a national and regional initiative that aims to unlock the unique genetic character of southern African populations. Its vision is to improve quality of life through understanding human genetic diversity. It is timely to advance the SAHGP initiative since global genomic initiatives are increasingly pointing to populations in Africa, more specifically the San and Khoe from southern Africa, as harbouring the most ancient genetic signatures among the living populations of the world. Studies on African populations have already generated a wealth of information upon which the SAHGP can build. This information will be used to promote and support genomic research programmes both nationally and regionally to address critical questions that would benefit the people of our region. The SAHGP aims to make a significant contribution to the understanding of DNA variation among southern Africans and how this impacts on the health of the people of this region. Aims of the SAHGP: To develop capacity for genomic research in southern Africa; To establish sustainable resources for genomic research in the region; and To translate knowledge and information into improvements in human health in the region. The objective is to derive the maximum benefit from the SAHGP, and that the data should be widely shared with the scientific community for the benefit of the people of the sub-continent and beyond.

  Study EGAS00001002639

• EGA file encryption types

  EGA file encryption The European Genome-Phenome Archive (EGA) stands as a significant initiative in the field of genomics, facilitating the secure storage and sharing of vast amounts of genomic data. Jointly hosted by the Centre for Genomic Regulation (CRG) and the European Bioinformatics Institute (EMBL-EBI), the EGA offers a robust infrastructure for managing encrypted data, ensuring the privacy and integrity of sensitive genomic information. Both CRG and EMBL-EBI play pivotal roles in the EGA, each institution bringing unique expertise in managing different types of encryptions. EMBL-EBI EGACryptor encryption system, while CRG utilises Crypt4GH, resulting in two distinct encryption file types: cip and c4gh, respectively. How can I check the file encryption? To access your dataset of interest on the European Genome-Phenome Archive (EGA) and determine the corresponding encryption file extension, please follow these step-by-step instructions: Utilise the search or navigation features provided on the EGA website to locate the dataset you are interested in. Once you find the dataset webpage, click on the "Files" tab, typically located on the dataset's webpage. Upon reaching the "Files" tab, you will be presented with a table containing comprehensive information about the files associated with the dataset. This table will include various columns, such as "File Name," "Size," and "Location." The "Location" column is particularly relevant for determining the encryption file extension. Figure 1: File table showing all the information available for the files in a dataset. This table is specific for each dataset. To identify the encryption file extension corresponding to a specific file, locate the "Location" column in the table. If the file is archived in Spain, the file will have the .c4gh extension, indicating that it is encrypted using Crypt4gh. Conversely, if the file is archived in the UK, the encrypted file extension will be .cip, indicating the usage of EGACryptor for encryption. It is worth noting that a file can be available in both locations, meaning it will be accessible with both file extensions (.c4gh and .cip). This allows users to choose the encryption method that aligns with their preferred platform or analysis tools.

  Documentation check-encryption-type

• Treg cell subset-specific gene expression patterns in human head and neck cancer

  Backgrand: The occurrence of head and neck cancer has been increased all over the world. Although the prognosis has been improved by using several treatment modalities including immunotherapy, it is still unsatisfying. It is still unclear why the immunotherapy is effective only for partial amount of patients. To resolve this problem and to make a new treatment strategy based on human immune system, further investigation of antitumor immunity is required. Regulatory T (Treg) cells play critical roles in human immune responses including antitumor immunity. Therefore, the research to elucidate Treg function is strongly urged to clarify the mechanisms of antitumor immunity. Methods: We performed RNA-seuencing analysis of regulatory T cells infiltrating head and neck cancer. We devided into four populations, DP, CD25+, CTLA4+, DN and analyzed gene expressions. Results: The gene expression patterns of Treg-related genes were different between CD25+ cells and CD25- cells. Furthermore, DP cells had unique gene expression pattern compared to other populations. Conclusions: We found Treg cells infiltrating head and neck cancer had high expression levels of Treg-related genes and DP cells had unique gene expression pattern that may become a target of new treatment strategy. Regulatory T (Treg) cells play critical roles in human immune responses including antitumor immunity. Therefore, the research to elucidate Treg function is strongly urged to clarify the mechanisms of antitumor immunity.

  Study JGAS000135

• Gynecology and Lubricant Effects (GALE) Study

  The GALE study is a longitudinal study of the association between lubricant use and the vaginal microbiota in women receiving transvaginal ultrasound (TVUS) at the Diagnostic Radiology and Nuclear Medicine Department at the University of Maryland School of Medicine. Participants undergo a clinical exam at enrollment (at least 5 days prior to TVUS) and self-collect daily, mid-vaginal samples in the week leading up to TVUS, including immediately before the procedure. At the TVUS appointment, the sonographer applies a single-use packet of Glide lubricating jelly to the probe. The product was selected for study as it was currently being used in the TVUS clinic at the University of Maryland Medical Center and is a clinical lubricant which is very similar in composition to many sex lubricants. Participants collect samples the evening after TVUS and present for a follow-up clinical exam within a week of TVUS. Participants continue to sample twice weekly for an additional 8 weeks (returning completed kits each week), complete daily health and behavior diaries, and attend one final clinical exam at week 10. The clinician evaluates participants for bacterial vaginosis (BV) at each clinical visit using Amsel's criteria, and also looks for signs of vulvovaginal candidiasis (VVC) and trichomonas using a wet mount.

  Study phs002211

• PRDM9 loss of function follow up from Born-in-Bradford Autozygosity sequencing

  In the autozygosity exome sequencing of Born-in-Bradford samples of Pakistani origin there is a mother who is homozygous for an apparent truncating stop codon in PRDM9, the gene responsible for localising recombination during meiosis. We plan to deep sequence mother and child with X10, and physically phase the mother with PacBio sequencing. We will use this data to identify recombination locations, and test whether these are consistent with the known fine scale recombination map. Data Access is controlled by the Wellcome Trust Sanger Institute DAC and the Born In Bradford Executive Group.

  Dataset EGAD00001001686

• Establishing Reliability for Quantitative EEG, Transcranial Doppler, Behavioral Outcomes and Optical Coherence Tomography in SWS: The Next Step toward Biomarker Development

  Sturge-Weber syndrome (SWS) is a rare, congenital syndrome with vascular malformations of the brain, skin and eye. The underlying cause of SWS is unknown and the extent of involvement varies greatly from patient to patient. Those with brain involvement present with seizures, stroke-like episodes and neurologic deficits, usually in infancy. Those with eye involvement frequently develop vision threatening glaucoma and retinal injury. Treatment has been largely symptomatic and hampered by delayed diagnosis and the rarity of the condition. The purpose of this study is to determine the reliability of non-invasive measures to be developed as biomarkers for SWS and to determine inter-rater reliability where appropriate. This includes measuring reliability for: Power asymmetry on Quantitative Electroencephalogram Asymmetry of Transcranial Doppler velocity and pulsatility Behavioral outcome measures (PEDI, Erhardt, Modified Rankin Scale) Optical Coherence Tomography Approximately 40 subjects will participate in this observational, cross-sectional study. The first version study release included data of the first n=25 subjects.

  Study phs001281

• DNA Methylation Analysis of Peripheral Blood Cells from Siblings Discordant for ASD

  Autism is a common disorder whose causes are poorly understood. Both genetic and environmental influences are thought to act together causing autism. Epigenetics is an area that bridges genetic and environmental influencing and commonly is studied by examining dynamic methylation changes to the DNA. We have screened a total of 78 autistic boys and their fathers by this method in 807 genes and find 116 methylation changes that together can correctly identify nearly 80% of the affected boys from their fathers. We propose to confirm these exciting data in a much larger set of genes in 1,200 autistic boys and their families, including unaffected brothers. These data not only could provide new insight into the causes of autism but could also result in a screening test for autism.

  Study phs000619

• Longitudinal Studies of Patients with Familial Platelet Disorder with Associated Myeloid Malignancy (FPDMM)

  FPDMM (OMIM #601399) is a rare autosomal dominant disease characterized by defective megakaryocytic development, thrombocytopenia, platelet functional defects, and a life-long risk of developing hematological malignancies. FPDMM is caused by germline mutations in the RUNX1 gene, which encodes a master regulator of hematopoiesis. The overall lifetime risk of hematological malignancies in FPDMM patients is 35 - 45%. It is hypothesized that mutations in other genes cooperate with the germline RUNX1 mutations for leukemia development. However, it is not clear which genes need to be mutated for leukemia to develop and which biomarkers or clinical tests can be used to predict which patients will progress to leukemia. Likewise, there are no treatments and/or preventative measures that can reduce or stop disease progression except for stem cell transplantation, which is not available for all patients and may be associated with significant complications. To address these questions, we launched a longitudinal natural history study of patients associated with RUNX1 germline mutations at the NIH Clinical Center in early 2019 (Trial Registration ID: NCT03854318). The goals of this study are to: (1) perform comprehensive longitudinal phenotyping of FPDMM patients to document the full spectrum of both hematopoietic and non-hematopoietic manifestations of the disease; and (2) perform extensive genomic analyses of FPDMM patient samples to identify cooperating genomic variants, which may confer growth advantage that leads to clonal expansion of affected hematopoietic cells that may serve as the precursor to malignancies. The data available through dbGaP include exome sequencing and RNA-seq data from these patients. Diverse germline mutation types were identified in the RUNX1 gene, including splice site mutations and large deletions, in addition to nucleotide substitutions and small indels. Somatic mutations, especially in genes associated with clonal hematopoiesis of indeterminate potential (CHIP), were found in a substantial proportion of FPDMM patients who were leukemia-free. The findings suggest that the genomes in these patients are prone to somatic mutations and monitoring the dynamic changes of these somatic mutations prospectively may provide a way to predict progression to malignancies.

  Study phs003075

• The Multiethnic Cohort (MEC) Study

  The Multiethnic Cohort (MEC) study of over 215,000 men and women in Hawaii and California is unique in that it is population-based and includes large representations of older adults (45-75 years at baseline) for five US racial/ethnic groups (Japanese Americans, African Americans, European Americans, Latinos and Native Hawaiians) at varying risks of chronic diseases. The MEC has established a large biorepository of mainly blood and urine collected from over 70,000 participants, linked to extensive, prospectively collected risk factors (e.g., diet, smoking, physical activity), biomarkers and clinical data for five racial/ethnic groups.

  Study phs002183

• Center for Common Disease Genomics [CCDG] - Cardiovascular: Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors

  This study is a part of NHGRI's Center for Common Disease Genomics, which is a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Current estimates anticipate that the CCDG program will sequence approximately 140K whole genomes and 225K whole exomes during the life of the project. The Cardiovascular Disease working group of the CCDG considered five diseases: early-onset coronary artery disease (EOCAD), stroke, atrial fibrillation, congestive heart failure and type 2 diabetes. Atrial fibrillation will affect between 6-12 million individuals in the US by 2050. AF also is associated with increased risks of stroke, dementia, heart failure, death, and high health care costs. Many risk factors for AF have been identified, including advancing age, cardiovascular disease (CVD), and CVD risk factors. However, there is little knowledge how to prevent AF. Furthermore, therapies for AF are only partially effective, and are themselves associated with substantial morbidity. Previously, heritable forms of AF have been considered rare; yet in the last decade, it has been established that AF, and in particular early-onset forms of AF, are heritable. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. The AFGen Consortium currently consists of investigators from more than 25 studies with >20,000 individuals with AF and >100,000 without AF. In the latest analyses, 14 loci have been identified for AF1. Broadly, the loci implicate genes related to cardiopulmonary development, cardiac-expressed ion channels, and cell signaling molecules. Source: ccdg.rutgers.edu The GAPP study is an ongoing national population-based prospective cohort study conducted in the Principality of Liechtenstein. Between 2010 and 2014, all inhabitants of Liechtenstein aged 25-41 years old were asked to participate in the study, and 2170 could be enrolled. The aim of the study is to identify the determinants of blood pressure and other cardiovascular risk factors and their progression over time. A large number of baseline characteristics and health information as well as several blood, urinary and genetic markers were collected. The samples were sent to The Broad Institute of MIT and Harvard to generate genetic data using whole exome sequencing and whole genome genotyping (Infinium Global Screening Array); all samples serving as controls.

  Study phs002236

• Genome-Wide Association Studies of Prematurity and Its Complications

  Preterm labor resulting in the delivery of a premature child is a complex problem with an enormous impact on individuals, families and society. An estimated 500,000 children are born prematurely in the U.S. each year, and 5 million worldwide die annually of prematurity and its complications. Prematurity is also the single largest contributor to disability-adjusted life years, a measure of the lifetime impact of a disease. Despite the importance of the problem and its disproportionate occurrence in poor and minority populations, its underlying etiology (or etiologies) remains unknown; the single best predictor for preterm delivery is a previous preterm birth. The largest single cause of prematurity is spontaneous preterm labor, and suspected triggers for this include infection, stress, poor nutrition and genetic factors. Family and twin studies provide strong evidence that genetic factors underlie about 40% of the risk for prematurity. A major challenge in studying genetic factors in prematurity is maternal/uterine factors, fetal/placental factors, or both may influence risk. Thus, any approach to studying preterm birth should account for both infant and maternal risk, environmental covariates and interactions. The Danish National Birth Cohort (DNBC) is a well-established, prospective cohort that enrolled women early in pregnancy, prior to any adverse pregnancy outcomes, to minimize bias in data collection and sampling. See details at: http://www.ssi.dk/English. The DNBC followed over 100,000 pregnancies beginning in the first trimester and has extensive biological material and epidemiologic data on health outcomes in both mother and child. The current study posted on dbGaP contains data from a genome-wide case/control study using approximately 1,000 preterm mother-child pairs from the DNBC most with spontaneous onset of labor or preterm premature rupture of membranes (PPROM), along with 1,000 control pairs where the child was born at ~40 weeks' gestation. After data cleaning some small changes in case/control status and other variables resulted in minor changes in numbers of cases or controls in certain categories. Environmental variables are being used as covariates in the analysis. To replicate positive findings, we are using additional mother-child pairs from the DNBC and from the general Danish population, as well as 2200 samples coming primarily from an African-American population known to have high rates of preterm labor and delivery. This group includes over 1000 mostly very low birthweight infants, over 500 infant term controls, 326 term mother/baby pairs and 180 preterm mother/baby pairs. The data from these additional cohorts will be available in separate dbGaP postings. The study is expected to yield a better understanding of the biology of parturition, identify common genetic factors that play a role in preterm birth and its complications and suggest environmental modifications that can prolong gestation, with the goal of improving both neonatal and adult outcomes. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to prematurity and its complications through large-scale genome-wide association studies of a well-characterized cohort of Danish mothers and babies. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000103

• ICGC PedBrain: Deep-sequencing of childhood brain tumors.

  Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.

  Study EGAS00001000215

• Genome-wide NanoRCS of cfDNA from plasma of healthy individuals

  Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant molecules, extremely sensitive sequencing methods are required. We adapted a new technique, NanoRCS, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule for genome-wide sequencing, and applied this to plasma of healthy controls.

  Study EGAS50000000695

• PDAC Phenotype and Germline Genotype Data Access Committee

  This Data Access Committee (DAC) is responsible for reviewing and approving requests for access to controlled phenotype metadata and derived germline FUT2/FUT3 genotype data from patients with pancreatic ductal adenocarcinoma (PDAC). Access is granted to bona fide researchers for non-commercial research purposes only, subject to approval by the DAC and in accordance with the original informed consent and applicable ethical regulations.

  Dac EGAC50000000893

• Transcriptomics_of_human_olfactory_mucosa

  The olfactory gene repertoire is largely species-specific, shaped by the nature and necessityof chemosensory information for survival in each species' niche. We are intrigued by thisinterspecific variation and started to investigate the olfactory transcriptome in primates forevidence of selection at the level of receptor gene choice. Having collected this data fromtwo primates, we now wish to extend the analysis to humans.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/

  Study EGAS00001001486

• Advancing fast in the analysis of circulating tumour DNA

  In cancer patients, solid tumours also release DNA fragments into the blood, and they are called Circulating Tumours DNA (ctDNA). Nowadays, the standard procedure for cancer monitoring is analysis of surgically obtained biopsies. They generate a big amount of material, but the operation is highly invasive and provide medical doctors with a single-time snapshot of the tumours, which are often highly changeable. Analysis of ctDNA, on the other hand, can provide continuous information regarding the tumour itself without the need of invasive procedures. This is why interest in this method is growing, and with it, the need for its technological optimization. Guanhua Zhu and colleagues, at the Genome Institute of Singapore, developed a methodology to quantify ctDNA burden, which means to estimate the amount of tumours derived circulating DNA among all cell-free DNA in the blood of individuals. Their work, published in Nature Communications in april 2021 and summarized in a sketch below, uses state-of-the art methods to analyse cfDNA degradation patterns at promoters and exon regions, to discern it from the DNA coming from the tumours. The bright point of their approach is that simultaneously enable for profiling of actionable cancer mutations and quantitative estimation of ctDNA burden. Their sequencing data of ctDNA has been deposited in the EGA under the accession number EGAS00001004657. This study sums up to a total of 37 of cfDNA and 36 about ctDNA present up to date in the EGA archive. The existence of cfDNA was firstly described back in 2002, while the use of ctDNA analysis in the oncological field exploded only after 2016. The approach is rapidly evolving, moving in parallel with the ever-improving sequencing technologies. Especially, the possibility to obtain high quality sequences from minimal amount of material is a crucial factor. Being able to alleviate cancer patients of disturbing and often slow-recovery procedures, while at the same time improving the quality of diagnosis and disease monitoring seems like a lot to ask. Thankfully, we are blessed with brilliant and dedicated scientists from all around the world who collaborate to make this a reality, sharing their results, knowledge and data.

  Blog advancing-fast-in-the-analysis-of-circulating-tumour-dna

• UK renal cancer samples genotyped on Illumina OmniExpress BeadChip

  Renal cell carcinoma (RCC) cases comprised adult patients with histologically proven RCC were collected through two sources within the UK. First, 856 cases from SORCE, a MRC collection of surgically treated RCC cases ascertained through UK clinical oncology centres. Second, 189 RCC cases collected through the ICR and Royal Marsden NHS Hospitals Trust. Cases included 590 clear cell carcinomas (CCCs), 42 papillary carcinomas (PCs), 33 chromophobe carcinomas (CCs) and 19 mixed or other histological subtypes. DNA was extracted from EDTA-venous blood samples using the conventional methods and quantified using PicoGreen (Invitrogen). Cases were genotyped using the Human OmniExpress-12 BeadChip according to the manufacturer's recommendations (Illumina Inc, San Diego, CA, USA). After strict QC, 944 cases were retained. Data provided in plink format. Controls used were data from the Wellcome Trust Case Control Consortium 2 (WTCCC2) 1958 birth cohort and the UK Blood Service Control Group (available as EGAS00000000028).

  Study EGAS00001002336

• Analysis of Epigenomes and Genome Topology in Colorectal Cancer

  When diagnosing cancer, pathologists use nuclear morphology as a hallmark of tumor cells, but the topological changes linked to alterations in the shape of the nucleus were poorly understood. To uncover the molecular changes that occur in the 3D structure of cancer genomes, we integrated topological maps for colon tumors and normal colon tissues with epigenetic, transcriptional, and imaging data. We characterized tumor-associated changes in chromatin loops, topologically associated domains (TADs), and large-scale compartments. We found that chromatin loop rewiring contributes to oncogenic gene expression programs. Whereas TAD structures are largely stable, the spatial partitioning of the open and closed genome compartments is compromised in tumors and is accompanied by hypomethylation and histone mark rearrangements. We also identified a compartment that is reorganized in tumors and is at the interface between the canonical A and B compartments. Similar changes were evident in non-malignant cells that had accumulated excessive cellular divisions. Our analyses suggest that these compartment changes repress stemness and invasion programs while inducing immunity genes, and they may therefore restrain malignant progression.

  Study phs002288

• RNAseq data to study PRPF6 regulated splice forms in colon cancer cell lines

  Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.

  Study EGAS00001000761

• scRNAseq of human primary nasal epithelium differentiated at air-liquid interface exposed to SARS-CoV2

  The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human primary nasal epithelium differentiated at air-liquid interface.

  Study EGAS00001005633

• TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism

  DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism/Seckel syndrome. We establish that TRAIP relocalizes to sites of DNA damage where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to UV irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a novel component of the DNA damage response to replication-blocking DNA lesions.

  Study EGAS00001001501

• Genomic profiling of Follicular thyroid adenomas and carcinomas using exome-sequencing analyses

  While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed an genomic profiling of 54 fresh frozen Follicular like thyroid samples using a whole exome sequencing approach (SureSelect V6 Target enrichment protocol and the Illumina Novaseq 6000 platform)

  Study EGAS00001005561