15020 results for "cancer studies using rna-seq"

in 19.30 milliseconds.

• Data upcycling, powered by EGA

  In 2012 a collaborative effort headed by the teams of Carlos Caldas in Cambridge, UK and Samuel Aparicio, Canada, produced a pivotal study aimed at defining the mutational landscape of breast cancer. They gathered a collection of over 2000 breast cancer samples (METABRIC) associated with long-term clinical follow-up. They delineated an array of inherited and somatically acquired genetic variants and associated them to gene expression. This led to the identification of putative cancer-driving events and improved stratification of breast cancer patients. The study elicited huge attention and was tackled as herculean effort by fellow researchers. Cristina Curtis and her colleagues deposited the data in the EGA archive (EGAS00000000083). What they probably could not foresee is that their data would be reused more than 100 times, becoming one of the most downloaded datasets at EGA. In 2015, Frederik S. Varn and colleagues accessed the above-mentioned data from the New Hampshire, USA, to correlate it to transcriptional programs of hematopoietic cells infiltrated in breast tumours and found that those can influence patients' prognosis. Their findings, published in Nature Communications, improved the understanding of the interplay between immune system and cancer. Again, in 2017 the dataset was downloaded by an Italian/Polish collaboration and used to corroborate their mechanistic study that demonstrate how a long non-coding RNA (lncRNA) is aberrantly localized into the chromatin, where it modulates oncogenic isoforms expression, thus contributing to breast cancer. To date, the METABRIC dataset has been reused to contribute to 147 publications. Its impact on breast cancer research is incalculable, and it even spread beyond that, with recent contributions to the understanding of pan-cancer mechanisms and features. Some of the publications are translating into improvements in diagnosis and treatment of different types of breast cancer. This is just an example of how data upcycling can amplify the potential of any dataset, well past the scope of its creation, the imagination of its owners and any geographical border. At EGA, we are proud to empower such fruitful worldwide cycles of knowledge, providing a platform that enables safe sharing of sensitive genetic data.

  Blog data-upcycling-powered-by-ega

• COVID-19 scRNA-seq, TCR-seq and BCR-seq

  COVID-19 scRNA-seq, TCR-seq and BCR-seq for 291 samples collected from 109 patients. Among 291 samples, 249 of them have two libraries (sequencing runs) for each assay, while 42 have only one library.

  Dataset EGAD00001007995

• Oropharynx cancers sequencing study (RNA-seq from FFPE)

  This is a study of transcriptomics in HPV-associated oropharynx tumors. The goals of this study were to characterize HPV+ oropharynx tumor subtypes and to examine HPV integration events and their downstream effects. HPV-host fusion transcripts and recurrent HPV integration genes were identified. Various alternative isoforms and splicing events of HPV genes were also studied. Multiple potential biomarkers of prognosis were associated with clinical outcomes.

  Study EGAS50000000893

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Abstract: Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Dataset EGAD00001011360

• Transcriptomic response of miRNAs of monocytes to bacterial and viral stimuli assessed by RNA-seq in Africans and Europeans

  Leveraging the miRNA transcriptome of 977 samples, the study aims to define the levels of miRNA and isomiR diversity across individuals and populations, explore the genetic sources of miRNA expression variability and miRNA-environment interactions, evaluate the effects of immune challenges upon miRNA and isomiR expression dynamics, and quantify the relative impact of transcription and miRNA-mediated degradation on gene expression variability.

  Study EGAS00001004192

• Cell line data (RNAseq, ATACseq, ChIPseq)

  Content: 2 GB RTK I cell lines (LN229, ZH487) in two conditions (NT control and shSOX10). RNAseq: single replicates per condition, polyA+ RNA sequencing, SE. ATACseq: biological replicates per condition, SE. ChIPseq (histone H3 modifications, LN229 only): all marks for each condition were pooled and sequenced on two lanes for each pool. ChIPseq (BRD4 and SOX10): SOX10 libraries were sequenced on single lanes. BRD4 samples were multiplexed and sequenced in two lanes. ChIPseq input samples are also included. Data type and technology: RNAseq: SE 50bp sequenced on HiSeq2000/4000. ATACseq: SE 50bp sequenced on HiSeq2000/4000. ChIPseq: SE 50bp sequenced on HiSeq2000/4000.

  Dataset EGAD00001005493

• Multi-omics data of 1000 Inflammatory Bowel Disease patients

  Portal available at https://1000ibd.org Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal (GI) tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data are generated from the same IBD patients.We initiated the 1000IBD project to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1,215 participants have been enrolled in the project and enrolment is on-going, with 609 patients being present in the first data release. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses, and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing.All molecular data generated within the 1000IBD project will be shared in multiple data on the European Genome-Phenome Archive (www.ega-archive.org). The first data release, will contain basic phenotypes for 609 participants, genotypes of 314 participants, gut microbiome data generated by tag sequencing the 16S gene of feces from 315 participants and intestinal biopsies from 107 participants, and gut microbiome metagenomic sequencing of feces of 355 participants . Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models.

  Study EGAS00001002702

• 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

• Common Variation in Candidate Genes in the Diabetes Prevention Program

  The Diabetes Prevention Program (DPP) was a multicenter controlled clinical trial examining the efficacy of an intensive lifestyle intervention or metformin to prevent or delay the development of diabetes in a population selected to be at high risk due to the presence of impaired glucose tolerance (IGT) and obesity. Development of diabetes, defined by 1997 American Diabetes Association (ADA) criteria, was the primary outcome while cardiovascular disease and its risk factors were important secondary outcomes. The pharmacological intervention was double blinded and placebo controlled. After randomization, participants had quarterly clinical evaluations and had, in addition, a fasting plasma glucose at semi-annual visits and a 75 gram oral glucose tolerance test at annual visits. Volunteers were recruited from populations known to be at particularly high risk for impaired glucose tolerance and type 2 diabetes including the following: persons with a family history of NIDDM, the elderly, overweight individuals, women with a history of diabetes during pregnancy ("gestational diabetes"), and minority populations including African Americans, Hispanic Americans, Asian and Pacific Island Americans, and Native Americans. The primary focus of the genetic investigations have been on candidate genes, including candidates derived from GWAS of diabetes, lipid and glycemia-related phenotypes. Please note more phenotype data for the DPPG cohort is available through the NIDDK Data Repository. Information on obtaining this phenotype data can be found by going to https://www.niddkrepository.org/studies/dppos/?query=DPP and https://www.niddkrepository.org/studies/dpp/?query=DPP. Data will need to be requested from both data sets. A linking file will be available to the NIDDK Data Repository.

  Study phs000681

• Age related Macular Degeneration (AMD)-- Michigan, Mayo, AREDS, Pennsylvania (MMAP) Cohort Study: A Joint Genome Wide Association Study

  Age-related Macular Degeneration (AMD) is a leading cause of incurable blindness in people over the age of 65. AMD is a late-onset multi-factorial neurodegenerative disease and its pathogenesis involves interaction of genetic and environmental factors. Several chromosomal regions have been associated with AMD susceptibility through linkage analysis (Swaroop et al., 2009). More recent studies provide strong evidence that variants within the CFH gene cluster on chromosome 1 and at/near LOC387715/ARMS2 on chromosome 10 are strongly associated with disease. Variants at other genes including C2/BF, C3, CFI and APOE4, also contribute to AMD susceptibility. Our primary goals are to identify genetic variants and haplotypes that are associated with AMD. The underlying hypothesis is that DNA variation(s) in multiple genetic susceptibility loci will predispose individuals to AMD pathogenesis, and comparison of DNA of cases and controls should identify these susceptibility variants. Our studies are focused on the genetic analysis of advanced AMD and should provide novel insights into disease diagnosis, progression and pathology. We have assembled a collaborative group of researchers from the University of Michigan, Mayo Clinic, University of Pennsylvania, and the AREDS group including National Eye Institute intramural investigators, who collected clinical data and DNA from a large number of patients affected with AMD and from unaffected controls. The primary source of funding was National Eye Institute. Through this collaborative effort, we submitted and obtained usable genotyping data on 2184 patients and 1155 controls from the Center for Inherited Disease Research (CIDR).

  Study phs000182

• dbGaP Collection: Open Translational Science in Schizophrenia (OPTICS)

  Schizophrenia is a chronic, severe, disabling brain disorder that affects approximately 1% of the population worldwide. Epidemiologic studies have clearly demonstrated that genetics play a strong role in etiology, but the inheritance is very complex. Innovative analytic approaches and creative ways of combining disparate data sets will be necessary for making breakthroughs in identifying causal pathways and ultimately new drug targets. This dbGaP Collection consists of all genetic studies of schizophrenia available in dbGaP that have been consented for general research use. The goal is to facilitate identification of datasets with related scientific content in order to expedite the application process and ascertainment of datasets of interest for increased scientific discovery. The Open Translational Science in Schizophrenia (OPTICS) Project, was launched by Janssen Research & Development, LLC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, with a group of leading research organizations including the National Institutes of Health, Yale University School of Medicine, Rutgers University and the Harvard T.H. Chan School of Public Health, to create a new forum for collaborative analysis of Janssen's schizophrenia clinical trial data and other publicly available data about schizophrenia with the goal of creating new models for conducting research. The OPTICS project is one part of a larger effort at Janssen and other Johnson & Johnson research companies to share clinical trials data to enhance public health and advance science and medicine. Qualified investigators and physicians may apply for access to anonymized clinical trials data from Janssen, for more information please visit https://sites.google.com/site/opticsschizophrenia/.

  Study phs000887

• Microsatellite data show recent demographic expansions in sedentary but not in nomadic human populations in Africa and Eurasia.

  The transition from hunting and gathering to plant and animal domestication was one of the most important cultural and technological revolutions in human history. According to archeologists and paleoanthropologists, this transition triggered major demographic expansions. However, few genetic studies have found traces of Neolithic expansions in the current repartition of genetic polymorphism, pointing rather toward Paleolithic expansions. Here, we used microsatellite autosomal data to investigate the past demographic history of 87 African and Eurasian human populations with contrasted lifestyles (nomadic hunter-gatherers, semi-nomadic herders and sedentary farmers). Likely due to the combination of a higher mutation rate and the possibility to analyze several loci as independent replicates of the coalescent process, the analysis of microsatellite data allowed us to infer more recent expansions than previous genetic studies, potentially resulting from the Neolithic transition. Despite the variability in their location and environment, we found consistent expansions for all sedentary farmers, while we inferred constant population sizes for all hunter-gatherers and most herders, which could result from constraints linked to a nomadic or semi-nomadic lifestyle and/or competition for land between herders and farmers. As an exception, we inferred expansions for Central Asian herders. This might be linked with the arid environment of this area, which may have been more favorable to nomadic herders than to sedentary farmers. Alternatively, current Central Asian herders may descent from populations who have first experienced a transition from hunter-gathering to sedentary agropastoralism, and then a second transition to nomadic herding.

  Study EGAS00001000652

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. 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 EGAS00001003136

• Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants

  De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann-Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype-phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.

  Study EGAS00001003521

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. 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 EGAS00001003137

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. 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 EGAS00001003139

• Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma

  Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking. Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype-phenotype interrelation in PMBL. We identified highly recurrent oncogenic mutations in the JAK-STAT and NF-kB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, PDCD1LG2). Our analyses highlight the IRF-pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB and EP300 mutations driving oncogenic signaling. The identified driver genes were significantly more frequently mutated in PMBL as compared to diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relationship between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic work-up and therapeutic decision-making.

  Study EGAS00001003746

• Systems biology of Colorectal Cancer

  Colorectal cancer (CRC) is one of the most common cancers in both males and females, and it is perhaps the best understood of all epithelial tumors in terms of its molecular origin. Yet, despite large amount of work that has concentrated on understanding of colon tumorigenesis, we still do not know the full complement of molecular lesions that are individually necessary – and together sufficient – to cause colorectal cancer. Neither do we understand why some specific mutations that are relatively rare in other tumors (e.g. loss of the APC tumor suppressor) are extremely common in colorectal cancer. We propose here to use the tools of systems biology to develop a quantitative and comprehensive model of colorectal tumorigenesis. The model will include identification of cell-type specific and oncogenic pathways that contribute to colon tumorigenesis, and explain in molecular detail how a genotype of an individual CRC leads to activation of downstream genes that drive uncontrolled cell growth. This model will subsequently be used to find novel therapeutic targets, to guide genetic screening to identify individuals with elevated risk for developing CRC, and to classify patients into molecular subgroups to select the treatment combination that is optimal for each patient (personalized medicine). The specific objectives of the SYSCOL project are: 1. Identify genetic markers for individual risk using genotyping and sequencing of constitutional DNA from sporadic and familial CRC cases and controls 2. Identify genes and regulatory elements that contribute to colorectal cancer cell growth 3. Use data from Aims 1-2 to develop a quantitative model for colorectal tumorigenesis 4. Apply the model for identification of high-risk individuals, for molecular classification of the disease, and for identification of novel molecular treatment targets

  Study EGAS00001000854

• Uncovering tumor intrinsic and extrinsic factors that regulate hepatocellular carcinoma growth using patient derived xenograft assays

  Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient derived xenograft (PDX) models. In Asia, HCCs from hepatitis B virus patients have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NSG mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the US. PDX models preserved the histology and genetic features of parental tumors, and ultimately, 9 new models were usable for pre-clinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib and CCA PDXs were also highly sensitive to regorafenib. PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the US.

  Study EGAS00001004020