21182 results for "fc 26 coins Buyfc26coins.com is EA Sports official for FC 26 coins The service is affordable and quick..JIZq"

in 24.94 milliseconds.

• RNA-seq, WGS and WES of Hepatocellular carcinomas, enriched in fibrolamellar carcinomas

  DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.

  Study EGAS00001003837

• CRLF2_sequencing_project_

  I hope to gain insight into novel genetic aberrations present in these patients that will highlightimportant pathways that are involved in this subtype of leukaemia. It would be interesting to see ifthe mutations and pathways that are activated are consistent between the patients, or differencesare observed dependent upon whether the patient has the translocation or the PAR1 deletion. Ofnote is the high association with either numerical gains of chromosome X or numerical/structuralabnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. Ihope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. Byincluding the three patients that are normal for CRLF2, but have consistent genetic abnormalitiesfound in the experimental cohort, I expect to find genetic differences between these two groupsthat will help us to identify novel molecular targets specific to CRLF2 deregulation.

  Study EGAS00001000080

• The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome

  Here we aimed to contribute to the description of the genetic architecture of Congenital heart defect (CHD) in Down syndrome (DS), and report the results of a genome-wide association study using samples from DS individuals with and without CHD. CHD is a common developmental defect of DS occurring in 40% of cases. This case-control GWAS includes 187 DS with CHD as cases, and 151 DS without CHD as controls.

  Study EGAS00000000129

• Genome-Wide Association Study of Endometrial Cancer in the Epidemiology of Endometrial Cancer Consortium (E2C2)

  Endometrial cancer, the most common gynecological malignancy in the United States, has both an environmental and genetic component. To this end, we conducted a genome-wide association study to identify genes involved in endometrial cancer using studies from the NCI-supported Epidemiology of Endometrial Cancer Consortium (E2C2). For the discovery stage we included samples from 6 cohort and 7 case control studies through 2007. The total number of cases genotyped were 2,307, white women of European descent, and 2,307 matched controls using the Illumina HumanOmniExpress platform. We conducted the replication using the Infinium HumanExome BeadChip, which successfully genotyped 177,139 variants in 1055 cases and 1778 controls from four ethnically diverse studies that are part of the Epidemiology of Endometrial Cancer Consortium (E2C2). The overall goal is to determine whether certain genotypes are predictive of future endometrial cancer risk, and whether the genotypes interact with established endometrial risk factors.

  Study phs000893

• Gabriella Miller Kids First Pediatric Research Project in Cornelia de Lange Syndrome, Related Diagnosis and Structural Birth Defects

  This study involves a cohort of 400 individuals and family members with Cornelia de Lange Syndrome (CdLS) and CdLS-like phenotypes for which a molecular etiology has not yet been established. CdLS is a developmental disorder characterized by development delays, cognitive impairment, short stature, hearing loss, specific facial features, and structural birth defects such as differences of the limbs, heart, kidneys, and GI tract. Our approach to tease out genetic contributions to birth defects has been to identify the underlying causes of syndromic birth defects which are often Mendelian in nature and therefore lend themselves more readily to genetic causal identification. Once identified, these genetic causes of syndromic forms of birth defects can be leveraged to understand the genetic contributions to isolated birth defects seen in constellation in syndromes such as CdLS. This work will lead to the identification of genes critical in human embryonic development, provide novel insights into transcriptional regulation and help to identify genetic causes and candidate genes for isolated birth defects seen in constellation in similar diagnoses.

  Study phs002174

• Single cell RNA sequencing of synovial B cells in early Rheumatoid Arthritis

  Rheumatoid Arthritis (RA) is a prevalent autoimmune disease characterized by inflammation of the peripheral joints and occurence of autoantibodies, i.e. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA), in circulation. Previous studies have shown that there are memory B cells and autoantibody producing plasma cells present in the joint tissue of patients with long-standing RA. However, it has remained unclear, whether these B cell populations are already present in the joint tissue of patients at the disease onset and whether these are autoreactive. Here, we used a single cell RNA sequencing approach to dissect the B cell repertoire at this early timepoint. We found evidence for B and T cell interaction and presence of memory and plasma cell pools in ACPA- and ACPA+ RA. Our results demonstrated clonal relationships between the memory and plasma cell compartments and autoreactivity within the plasma cell pool. These findings challenge our understanding of the local adaptive immune response in the joints of ACPA- and ACPA+ RA patients with direct implications for B and T cell targeting therapy in both patient subgroups.

  Study EGAS00001005144

• Adoptive Cell Therapy of Autologous T cell Receptor-Engineered T Cells Targeting the p53 Neoantigens in Human Solid Tumors

  Adoptive T cell therapy (ACT) using T cell receptor (TCR)-engineered T cells can mediate regression of advanced human cancers. How TCR-transduced T cells change post-ACT in vivo is currently not well understood. We screened 78 patients for TP53 mutations by whole exome sequencing and whole transcriptome sequencing. Of the 78 patient samples, 49 patient samples were previously reported (phs001003) and 2 additional patients were reported in phs002735. In this accession we report the sequencing data of remaining 23 patients and include 6 additional samples from previously published patients. Additionally, we treated a patient with chemo-refractory breast cancer that expressed mutant p53 R175H with autologous T cells transduced with an allogeneic TCR targeting p53 R175H with human leukocyte antigen (HLA) restriction of A*02. The patient had a partial response for 6 months with 55% tumor regression. The T cells from the infusion product and the peripheral blood T cells at 6 weeks post-ACT were analyzed using 10X single cell transcriptome analysis.

  Study phs002928

• NIH RECOVER-Pediatric: Understanding the Long-Term Impact of COVID on Children and Families

  The NIH Researching COVID to Enhance Recovery (RECOVER) initiative comprises a set of three combined retrospective and prospective, longitudinal and observational meta-cohort studies with nested case-control studies designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection (PASC or Post-COVID syndrome) in a diverse study population representative of the general COVID-19 population in the US. Enrolled patients, with and without known SARS-CoV-2 infection, will be observed for clinical signs and symptoms of PASC and will be assessed for risk and resiliency factors and potential mediating factors associated with the severity and progression of PASC. The objective of the RECOVER initiative is to enhance knowledge of recovery from SARS-CoV-2 infections in order to support development of novel diagnostic and therapeutic interventions. Overarching scientific objectives are as follows:Characterize the incidence and prevalence of sequelae of SARS-CoV-2 infection.Characterize the spectrum of clinical symptoms, subclinical organ dysfunction, natural history, and distinct phenotypes identified as sequelae of SARS-CoV-2 infection. Define the biological mechanisms underlying pathogenesis of the sequelae of SARS-CoV-2 infection. The RECOVER observational studies comprise three cohorts across the lifespan (adult, pediatric, and tissue pathology (autopsy)). The data collection and data analysis plans for each cohort have been harmonized to use common data elements where feasible. Brief descriptions of each cohort are provided in the following paragraphs: 1) NIH RECOVER: A Multi-site Observational Study of Post-Acute Sequelae of SARS-CoV-2 Infection in Adults (see phs003463)The RECOVER adult cohort study is a combined retrospective and prospective, longitudinal, observational meta-cohort of individuals who will enter the cohort with and without SARS-CoV-2 infection and at varying stages before and after infection. Individuals with and without SARS-CoV-2 infection, and with or without PASC symptoms, will be followed to identify risk factors and occurrence of PASC. This study will be conducted in the United States and subjects will be recruited through inpatient, outpatient, and community-based settings. Study data including age, demographics, social determinants of health, medical history, vaccination history, details of acute SARS-CoV-2 infection, overall health and physical function, and PASC symptom screen will be reported by subjects or collected from the electronic health record using a case report form at specified intervals. Biologic specimens will be collected at specified intervals, with some tests performed in local clinical laboratories and others performed by centralized research centers or banked in the Biospecimen Repository. Advanced clinical examinations and radiologic examinations will be performed at local study sites with cross-site standardization. 2) A Multi-Center Observational Study: The RECOVER Post Acute Sequelae of SARS-CoV-2 (PASC) Pediatric Cohort Study (this study)The RECOVER pediatric study is a combined retrospective and prospective, longitudinal, observational meta-cohort of individuals ages newborn-25 years who will enter the cohort with and without SARS-CoV-2 infection at varying stages before and after infection. Individuals with and without SARS-CoV-2 infection and with or without PASC symptoms will be followed to identify risk factors and occurrence of PASC. This study recruit participants inpatient, outpatient, and community-based settings in the United States. Study data including age, demographics, social determinants of health, medical history, vaccination history, details of acute SARS-CoV-2 infection, overall health and physical function, and PASC symptoms will be reported by participants or collected from the electronic health record using a case report form at specified intervals. Biologic specimens will be collected at specified intervals, with some tests performed in local clinical laboratories and others performed by centralized research centers or banked in the Biospecimen Repository. Advanced clinical and radiologic examinations will be performed at local study sites with cross-site standardization. 3) NIH RECOVER: A Multi-site Pathology Study of Post-Acute Sequelae of SARS-CoV-2 Infection The RECOVER tissue pathology study is a cross-sectional study designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection in a diverse population representative of the general COVID-19 population in the US. The autopsy study will characterize the pathology of PASC in (i) non-hospitalized patients who die 30 days or later from symptom onset of COVID-19, and (ii) hospitalized patients who die 30 days or later after discharge from a hospitalization for COVID-19. The study will include decedents who had previously fully recovered from SARS-CoV-2 infection (i.e., >30 days from onset in non-hospitalized, or >30 days from discharge in hospitalized patients), and decedents who meet clinical criteria of PASC as defined by the recent World Health Organization publication (see Section 5.4 below). The autopsy study will also explore the pathology of acute SARS-CoV-2 infection in a smaller subset of patients who died 15-30 days from symptom onset. This protocol defines the common set of clinical data elements, autopsy procedures for tissue collection, core measures, pathology protocols, shared pathology tissues, data elements, and methodology. Each investigator site is expected to perform autopsies on the decedents to address the pathophysiology of the potential long-term effects of SARS-CoV-2 infection on human health. The Consortium analysis plan aims to address research questions by incorporating: 1) tissue obtained from autopsies performed at each Phase II participant's site; and 2) tissue available from other pathology investigators/autopsy sites within the Consortium.

  Study phs003461

• Changes in alternative splicing and associated neo-antigens due to therapy

  Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.

  Study EGAS00001004524

• Correlates of Human Nerve Repair

  This is a longitudinal prospective cohort study in patients with carpal tunnel syndrome undergoing decompression surgery. Phenotypic data and skin biopsies were collected before and 6 months after surgery to determine molecular and cellular correlates associated with neural regeneration and neuropathic pain. RNA sequencing was performed in the skin samples and differential gene expression was determined post compared to pre surgery. The molecular changes identified in skin were correlated with the clinical phenotype representing neural regeneration.

  Study phs001796

• MutWP1: CRUK Grand Challenge Mutographs of Cancer: Colorectal_LCM (2020-02-20)

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development. . This dataset contains all the data available for this study on 2020-02-20.

  Dataset EGAD00001005994

• 10X single cell sequencing of HNT34 cocultured with Tcells with or without antibody targeting SLAMF6

  This dataset contains fastq-files from single cell 5' RNA sequencing of the AML cell line HNT34 and normal T cells following co-culture with and without an antibody blocking SLAMF6 (TNC-1). The libraries were prepared using 10X GEM-X Universal 5' Gene Expression v3 Reagent Kit. In total, the dataset contains sequenced gene expression libraries from four samples (HNT34 co-cultured with T cells from two different donors; for both donors there is one sample with and one sample without the blocking antibody).

  Dataset EGAD50000001573

• Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint

  The progression to severe COVID-19 arises predominantly from a dysregulated host immune response, although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of disease progression and restrains our understanding of “long COVID”. Here, we analyzed the transcriptomes of peripheral blood mononuclear cells collected from COVID-19 patients experiencing different degrees of the disease and control patients. In critical COVID-19 patients, we found an altered regulatory network involving microRNAs, long non-coding RNAs, and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. We also observed an upregulation of tRNA aminoacylation genes and increased expression of coding genes enriched for the cognate amino acids. Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by alterations in microRNA expression and tRNA metabolism.

  Study EGAS50000000965

• High density copy number analysis and whole exome sequencing of unselected chronic lymphocytic leukemia cases and of paired chronic lymphocytic leukemia and Richter Syndrome cases

  Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown since the full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains less than 20 clonally represented gene alterations/case, including predominantly non-silent mutations and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. While most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%) as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance. Genetic Lesions associated with Chronic Lymphocytic Leukemia transformation to Richter Syndrome Richter syndrome (RS) derives from the rare transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly of the diffuse large B cell type (DLBCL). The molecular pathogenesis of RS is only partially understood. By combining whole-exome sequencing and copy-number analysis of 9 CLL-RS pairs and of an extended panel of 43 RS cases, we show that this aggressive disease typically arises from the predominant CLL clone by acquiring an average of ~20 genetic lesions/case. RS lesions are heterogeneous in terms of load and spectrum among patients, and include those involved in CLL progression and chemorefractoriness (TP53 disruption and NOTCH1 activation) as well as some not previously implicated in CLL or RS pathogenesis. In particular, disruption of the CDKN2A/B cell cycle regulator locus is associated with ~30% of RS cases. Finally, we report that the genomic landscape of RS is significantly different from that of de novo DLBCL, suggesting that they represent distinct disease entities. These results provide insights into RS pathogenesis, and identify dysregulated pathways of potential diagnostic and therapeutic relevance.

  Study phs000364

• Transcriptomic Characterization of Human Innate T Cells

  We performed low input RNA-seq and single-cell RNA-seq on 7 lymphocyte populations with the objective of finding the common transcriptional programs shared among innate T cells. In brief, we drew blood from healthy donors and isolated CD4+ T cells, CD8+ T cells, Natural Killer cells, invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and two γδ T cell populations: Vδ1 and Vδ2. We performed low input RNA-seq on samples with 1000 cells each, for 6 healthy individuals, in duplicate. We performed single-cell RNA-seq with DNA-barcoded hashing antibodies to identify the cell type of origin for each cell. We found a common transcriptional program across lymphocytes that is gradually turned on as lymphocytes have a more "innateness" state, promoting effector functions and sacrificing proliferative capacity. Additionally, we performed low input RNA-seq for Vδ3-expressing γδ T cells and δ/αβ T cells for one healthy individual in duplicate (1000 cells per sample). This revealed δ/αβ T cells are transcriptionally more adaptive-like and Vδ3 more innate-like.

  Study phs002007

• Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer

  Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identified five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reasoned that their strong selection should prioritise them as key biomarkers for targeted therapies. We used primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number was associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC was statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway was independently observed in squamous lung cancer and triple negative breast cancer. These results suggest that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.

  Study EGAS00001006200

• IMPRESS: Improved methylation profiling using restriction enzymes and smMIP sequencing, combined with a new biomarker panel, creating a multi-cancer detection assay

  Background Despite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking. Methods We developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes. We used this technique for the development of a multi-cancer detection assay for eight of the most lethal cancer types worldwide. We selected 1791 CpG sites that can distinguish tumor from normal tissue based on DNA methylation. These sites were analysed with IMPRESS in 35 blood, 111 tumor and 114 normal samples. Finally, a classifier model was built. Results We present the successful development of IMPRESS and validated it with ddPCR. The final classifier model discriminating tumor from normal samples was built with 358 CpG target sites and reached a sensitivity of 0.95 and a specificity of 0.91. Moreover, we provide data that highlight IMPRESS’s potential for liquid biopsies. Conclusions We successfully created an innovative DNA methylation detection technique. By combining this method with a new multi-cancer biomarker panel, we developed a sensitive and specific multi-cancer assay, with potential use in liquid biopsies.

  Study EGAS50000000624

• Framingham Cohort

  Startup of Framingham Heart Study. Cardiovascular disease (CVD) is the leading cause of death and serious illness in the United States. In 1948, the Framingham Heart Study (FHS) -- under the direction of the National Heart Institute (now known as the National Heart, Lung, and Blood Institute, NHLBI) -- embarked on a novel and ambitious project in health research. At the time, little was known about the general causes of heart disease and stroke, but the death rates for CVD had been increasing steadily since the beginning of the century and had become an American epidemic. The objective of the FHS was to identify the common factors or characteristics that contribute to CVD by following its development over a long period of time in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke. Design of Framingham Heart Study. In 1948, the researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, and began the first round of extensive physical examinations and lifestyle interviews that they would later analyze for common patterns related to CVD development. Since 1948, the subjects have returned to the study every two years for an examination consisting of a detailed medical history, physical examination, and laboratory tests, and in 1971, the study enrolled a second-generation cohort -- 5,124 of the original participants' adult children and their spouses -- to participate in similar examinations. The second examination of the Offspring cohort occurred eight years after the first examination, and subsequent examinations have occurred approximately every four years thereafter. In April 2002 the Study entered a new phase: the enrollment of a third generation of participants, the grandchildren of the original cohort. The first examination of the Third Generation Study was completed in July 2005 and involved 4,095 participants. Thus, the FHS has evolved into a prospective, community-based, three generation family study. The FHS is a joint project of the National Heart, Lung and Blood Institute and Boston University. Research Areas in the Framingham Heart Study. Over the years, careful monitoring of the FHS population has led to the identification of the major CVD risk factors -- high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity -- as well as a great deal of valuable information on the effects of related factors such as blood triglyceride and HDL cholesterol levels, age, gender, and psychosocial issues. Risk factors have been identified for the major components of CVD, including coronary heart disease, stroke, intermittent claudication, and heart failure. It is also clear from research in the FHS and other studies that substantial subclinical vascular disease occurs in the blood vessels, heart and brain that precedes clinical CVD. With recent advances in technology, the FHS has enhanced its research capabilities and capitalized on its inherent resources by the conduct of high resolution imaging to detect and quantify subclinical vascular disease in the major blood vessels, heart and brain. These studies have included ultrasound studies of the heart (echocardiography) and carotid arteries, computed tomography studies of the heart and aorta, and magnetic resonance imaging studies of the brain, heart, and aorta. Although the Framingham cohort is primarily white, the importance of the major CVD risk factors identified in this group have been shown in other studies to apply almost universally among racial and ethnic groups, even though the patterns of distribution may vary from group to group. In the past half century, the Study has produced approximately 1,200 articles in leading medical journals. The concept of CVD risk factors has become an integral part of the modern medical curriculum and has led to the development of effective treatment and preventive strategies in clinical practice. In addition to research studies focused on risk factors, subclinical CVD and clinically apparent CVD, Framingham investigators have also collaborated with leading researchers from around the country and throughout the world on projects involving some of the major chronic illnesses in men and women, including dementia, osteoporosis and arthritis, nutritional deficiencies, eye diseases, hearing disorders, and chronic obstructive lung diseases. Genetic Research in the Framingham Heart Study. While pursuing the Study's established research goals, the NHLBI and the Framingham investigators has expanded its research mission into the study of genetic factors underlying CVD and other disorders. Over the past two decades, DNA has been collected from blood samples and from immortalized cell lines obtained from Original Cohort participants, members of the Offspring Cohort and the Third Generation Cohort. Several large-scale genotyping projects have been conducted in the past decade. Genome-wide linkage analysis has been conducted using genotypes of approximately 400 microsatellite markers that have been completed in over 9,300 subjects in all three generations. Analyses using microsatellite markers completed in the original cohort and offspring cohorts have resulted in over 100 publications, including many publications from the Genetics Analysis Workshop 13. Several other recent collaborative projects have completed thousands of SNP genotypes for candidate gene regions in subsets of FHS subjects with available DNA. These projects include the Cardiogenomics Program of the NHLBI's Programs for Genomics Applications, the genotyping of ~3000 SNPs in inflammation genes, and the completion of a genome-wide scan of 100,000 SNPs using the Affymetrix 100K Genechip. Framingham Cohort Phenotype Data. The phenotype database contains a vast array of phenotype information available in all three generations. These will include the quantitative measures of the major risk factors such as systolic blood pressure, total and HDL cholesterol, fasting glucose, and cigarette use, as well as anthropomorphic measures such as body mass index, biomarkers such as fibrinogen and CRP, and electrocardiography measures such as the QT interval. Many of these measures have been collected repeatedly in the original and offspring cohorts. Also included in the SHARe database will be an array of recently collected biomarkers, subclinical disease imaging measures, clinical CVD outcomes as well as an array of ancillary studies. The phenotype data is located here in the top-level study phs000007 Framingham Cohort. To view the phenotype variables collected from the Framingham Cohort, please click on the "Variables" tab above. The Framingham Cohort is utilized in the following dbGaP substudies. To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000007 Framingham Cohort. phs000342 Framingham SHARe phs000282 Framingham CARe phs000363 Framingham SABRe phs000307 Framingham Medical Resequencing phs000401 Framingham ESP Heart-GO phs000651 Framingham CHARGE-S phs000724 Framingham DNA Methylation phs001610 Framingham T2D-GENES phs002558 Framingham ADSP phs002559 Framingham BRIDGET phs002560 Framingham Cholesterol phs002611 Framingham Post-Mortem Brain Tissue phs002938 Framingham Molecular QTL The unflagging commitment of the research participants in the NHLBI FHS has made more than a half century of research success possible. For decades, the FHS has made its data and DNA widely available to qualified investigators throughout the world through the Limited Access Datasets and the FHS DNA Committee, and the SHARe database will continue that tradition by allowing access to qualified investigators who agree to the requirements of data access. With the SHARe database, we continue with an ambitious research agenda and look forward to new discoveries in the decades to come.

  Study phs000007

• Timing the landmark events in the evolution of clear cell renal cell cancer

  Clear cell renal cancer is characterized by near-universal loss of the short arm of chromosome 3 (3p). This event arises through unknown mechanisms, but critically results in the loss of several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cancer (ccRCC) recruited into the Renal TRACERx study. We find novel hotspots of point mutations in the 5'-UTR of TERT, targeting a MYC-MAX repressor, that result in telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. Using molecular clocks, we estimate this occurs in childhood or adolescence, generally preceding emergence of the most recent common ancestor by years to decades. Similar genomic changes recent common ancestor by years to decades. Similar genomic changes are seen in inherited kidney cancers. Modeling differences in age-incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Targeting essential genes in deleted regions of chromosome 3p could represent a potential preventative strategy for renal cancer.

  Dataset EGAD00001003445

• Genetic Components of Knee Osteoarthritis (GeCKO) Study: The Osteoarthritis Initiative

  The Osteoarthritis Initiative (OAI) is a publicly and privately funded prospective longitudinal cohort with a primary objective of identifying risk factors for incidence and progression of tibiofemoral knee OA. The OAI utilized a focused population-based recruitment to enroll 4,674 men and women between the ages of 45-79 years who either had radiographic symptomatic knee OA or who were without radiographic symptomatic OA in both knees but were considered high risk for OA because they had two or more known risk factors for knee OA. Subjects were recruited into the baseline phase of the OAI at multiple sites throughout the US between 2004 and 2006. All subjects were invited back for follow-up examinations to assess incidence or progression of OA annually, for up to 5 years. Phenotype data from the baseline and follow-up examinations are available for public access from the Osteoarthritis Initiative (OAI) database at http://www.oai.ucsf.edu/. The Genetic Components of Knee Osteoarthritis (GeCKO) Study was initiated in 2009 as a genetic ancillary study to perform a genome-wide association study to identify genetic variants associated with radiographic osteoarthritis. This study included 4,482 individuals participating in the parent OAI study. Following sample cleaning (e.g., removal of duplicates, sex mismatches, poor sample quality, etc.), the final sample set included 4,129 individuals.

  Study phs000955

• Spatial predictors of response to immunotherapy in microsatellite stable metastatic colorectal cancer

  Microsatellite stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI), prompting investigation into strategies to enhance sensitivity. The MAYA trial, which utilized temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesized that TMZ-induced hypermutation could sensitize tumors to ICI. This phase II trial met its primary endpoint, demonstrating durable clinical responses with TMZ combined with ipilimumab and nivolumab. To elucidate factors influencing response heterogeneity, we conducted multi-omic spatial profiling of samples from patients who participated in the MAYA trial, including baseline and on-treatment tissue and blood specimens. While increased neoantigen load following TMZ exposure did not consistently predict for deep responses, spatial profiling revealed key determinants. Lymphocyte proportions, particularly CD8+KI67+ cells, within stromal and tumor compartments, along with macrophage composition (CD68+CD163+ cells) at the tumor-stromal interface, were predictive of response. Treatment pressures dynamically altered the tumor microenvironment composition and activated peripheral immune cells. This study is the first to identify spatial predictors of response to this promising novel treatment approach for MSS CRC.

  Study EGAS50000001567

• DERMATLAS__SG_basal_cell_adenoma_and_adenocarcinoma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are SG basal cell adenomas and adenocarcinomas.

  Study EGAS00001007745

• DERMATLAS__SG_basal_cell_adenoma_and_adenocarcinoma_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are SG basal cell adenomas and adenocarcinomas.

  Study EGAS00001007746

• Anaplastic Thyroid Cancer aligned sequence data

  Sequence data in fastq format was aligned to the GRCH38 reference genome. Aligned sequence was preprocessed with GATK for Indel Realignment and Base Quality Score Recalibration. Duplicates were marked with Picard Mark Duplicates. Aligned sequence is in bam format. Details of the alignment can be found int he bam header. In total, data generated from 174 tumour samples 102 matched blood normal controls was aligned. Tumour samples were classified as Anaplastic Thyroid, Poorly-differentiated or well-differentiated cancers.

  Dataset EGAD00001004126

• Phenotype data for clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. This dataset includes clinical phenotype data.

  Dataset EGAD00001006200