20313 results for "Fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are efficient and quick always..Z2Xg"

in 48.31 milliseconds.

• Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals

  This study presents a methodology for detecting circulating tumor DNA (ctDNA) using deep whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive alternative to bisulphite sequencing. The method enables simultaneous analysis of genomic and methylomic data for multi-cancer detection and monitoring minimal residual disease. In a diagnostic accuracy study across various cancer types, it achieved 85.3% sensitivity and 88.8% specificity, with validation done using matched tumour biopsies. Additionally, in silico validation showed strong discrimination at low ctDNA levels. The approach also successfully tracks tumour burden and ctDNA shedding from precancerous lesions post-treatment, making it ready for further clinical testing.

  Study EGAS50000000715

• WGS bam

  We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Genome Sequencing (WGS) data from patient tumor, PDOX, and cell lines from our study.

  Study EGAS00001005159

• WES bam

  We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Exome Sequencing (WES) data from patient tumor, PDOX, and cell lines from our study.

  Study EGAS00001005160

• BAM files from capture-based targeted sequencing of 4 agressive B-cell lymphoma tumour samples (DLBCL-panel)

  This dataset contains BAM files from capture-based targeted sequencing of 4 agressive B-cell lymphoma tumour samples for cases 2, 3, 4 and 13. The sequencing panel used is a DLBCL-oriented panel containing 136 genes, described in Mozas P. et al., Hematol Oncol 2023.

  Dataset EGAD50000000802

• bulk RNA-Seq samples of CRC patients

  The dataset contains samples of 30 CRC patients (3 samples for each patient, tumor and 2 normal adjacent tissue sites, 90 samples in total). Dataset is composed by fastq file (paired end) type from bulk RNA-Seq.

  Dataset EGAD00001009635

• Single-cell proteo-genomic reference maps of the human hematopoietic system

  We have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all major hematopoietic cell types in healthy aging and leukemia. Please note raw and integrated gene expression data, cell type annotation, metadata and dimensionality reduction are available as Seurat v3 objects through figshare. Access links are https://figshare.com/s/0fda29b169c719223ee3 (97 surface marker, 9 individuals dataset), https://figshare.com/s/313b5739ff469dac8c01 (197 surface marker, bone marrow and blood dataset), https://figshare.com/s/901bcddb9ee18e226031 (97 surface markers and whole transcriptome dataset) and https://figshare.com/s/24e10bf129fae1918316 (97 surface marker, 15 AML datasets).

  Study EGAS00001005593

• NPY methylated ctDNA is a promising biomarker for treatment response monitoring in metastatic colorectal cancer

  Study EGAS00001006820

• Transcriptome analysis of human longitudinal whole blood samples from PCR-positive and PCR-negative adults following controlled inoculation with Influenza A (H3N2) virus.

  Transcriptome analysis of influenza A (H3N2) human challenge samples. Understanding of the transcriptomic profile of individuals in early influenza infection is limited. To investigate this, longitudinal whole-blood samples (n=178) were taken from adult participants following controlled inoculation with Influenza A H3N2 virus (sampling at baseline (0) and days 1, 2, 3, 7, 10 and 14 post-challenge). Most participants became influenza PCR-positive; a minority remained PCR-negative. Total RNA was extracted from PAXgene tubes before undergoing globin and rRNA depletion. DNA libraries were constructed using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina. All samples were then sequenced using Illumina NovaSeq 6000.

  Study EGAS50000000679

• Sequencing_of_patient_samples_who_received_immune_checkpoint_inhibition___WES___NKI

  DNA and RNA isolated from FFPE blocks of patients who received immune checkpoint inhibition (ICI) are sequenced with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.

  Study EGAS00001003154

• Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

  Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

  Study EGAS00001006186

• Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers

  DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutational consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb) – higher than all childhood and most cancers (>7000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerases epsilon or delta. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germline bMMRD (p<10e-13). Sequential tumor biopsy analysis revealed that bMMRD/polymerase mutant cancers rapidly amass an excess of simultaneous mutations (~600 mutations/cell division), reaching but not exceeding ~20,000 exonic mutations in <6 months. Thus implying a threshold compatible with cancer cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.

  Study EGAS00001001112

• Blood Group Genotypes and Phenotypes in Omani Blood Donors and Its Links With Susceptibility to Malaria

  The Omani population experienced endemic malaria prior to eradication in the late 1990's. Since malaria is known to be a strong selective pressure on the human genome, particularly at blood group associated loci, we aimed to understand how selective pressures from malaria may be affecting genetic variation at blood group loci. Blood samples were collected from 100 healthy, Omani blood donors. Serology testing for 10 clinically relevant blood groups and whole genome sequencing (WGS) to an average coverage of 16X were performed on all samples. Additionally, using the WGS data, genetic variants (SNPs and INDELs) were called for chromosomes 1 - 22 using GRCh38. We find signals of selection at the Plasmodium vivax associated locus, ACKR1 (the Duffy blood group), but not at any Plasmodium falciparum associated loci. We also characterized several previously undescribed blood group alleles in the Omani population affecting antigenic expression, mostly at the RHD, RHCE, and GYPB loci. The data available from this project include BAM files from 100 Omani samples aligned to GRCh38, per chromosome VCF files, and results from the serology tests for all 10 blood groups.

  Study phs003694

• Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys

  Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a model physiologically close to humans. Here, we establish a foundation for in vitro oogenesis in cynomolgus (cy) monkeys: cy female embryonic stem cells harboring one active and one inactive X chromosome (Xa and Xi, respectively) differentiate robustly into primordial germ cell-like cells, which in xenogeneic reconstituted ovaries develop efficiently into oogonia and, remarkably, further into meiotic oocytes at the zygotene stage. This differentiation entails a comprehensive epigenetic reprogramming, including Xi reprogramming, yet, as partly observed in vivo, Xa and Xi remain epigenetically asymmetric with incomplete Xi reactivation. In humans and monkeys, the Xi epigenome in pluripotent stem cells functions as an Xi-reprogramming determinant. We further show that developmental-pathway over-activations with suboptimal up-regulation of relevant meiotic genes impede in vitro meiotic progression. Cy in vitro oogenesis exhibits critical homology with the human system, including with respect to bottlenecks, providing a salient model for advancing human in vitro oogenesis.

  Study JGAS000573

• Profiling_the_Microbiome_of_Early_Life_Gut_Samples

  The human gut microbiome (GM), defined as the microorganisms that reside in the human gastrointestinal tract, has been identified as critical for normal intestinal development and physiology. However, to-date, the majority of studies characterizing the gut microbiome has relied on stool samples, thereby limiting insights into the regionality of the gut and how its microbiota differs along its length. As a result, this project seeks to profile the adjacent microbiota of various regions along the intestinal tract from pediatric intestinal tissue and their associated mucosal washes, enabling insights into tissue-specific microbiomes. Due to the expected low microbial biomass of these samples, donor stool (when available) will also be metagenomically profiled as positive controls, which will enable us to benchmark our low-biomass processing methods with existing protocols. By sampling pediatric patients of diverse ages and health statuses, this metagenomic data will also be valuable for understanding the gut microbiome of the developing human gut across time and space. 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 please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001008081

• Role of the Cervico-Vaginal Microbiome in Spontaneous Preterm Birth

  Preterm birth is the leading cause of neonatal morbidity and mortality. A failure to predict and understand the causes of preterm birth have limited effective interventions and therapeutics. From a cohort of 2,000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Modern and innovative Bayesian modeling of vaginal microbiota identified features of these communities associated with PTB. Seven bacterial taxa were shown to have relative abundances significantly associated with an increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of β-defensins significantly decreased the risk of sPTB associated with the vaginal microbiota in an ethnicity-dependent manner. These findings hold promise for the development of novel diagnostics that could more accurately identify women at risk for sPTB early in pregnancy and offer new therapeutic strategies that would include immune modulators and microbiome-based therapeutics to reduce this significant health burden.

  Study phs001739

• CLL Genome

  The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective. This study consists of two datasets. EGAD00001000023 described in the Nature paper (2011), Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia, and the dataset EGA00001000044 & & EGAD00001000083 described in the Nature (2011) paper, Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia.Additional data generated within the ICGC-CLL genome project can be found in studies EGAS00001000374 and EGAS00001001306

  Study EGAS00000000092

• Whole_genome_sequencing_in_a_multiplex_Crohn_s_disease_family

  In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD). At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease. Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS). These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals. We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.

  Study EGAS00001000060

• Contribution of allelic imbalance to colorectal cancer

  Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge, and unbiased CRISPR-Cas9 knockout and activation screens identified altogether 79 genes within AI peaks regulating cell growth. Genetic and functional data implicates loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.

  Study EGAS00001002966

• Custom long non-coding RNA capture enhances detection sensitivity in different human sample types.

  Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts that lack protein coding potential and display regulatory functions in various cellular processes. As a result of their cell- and cancer-specific expression patterns, lncRNAs have emerged as potential diagnostic and therapeutic targets. The accurate characterization of lncRNAs in bulk transcriptome data remains challenging due to their low abundance compared to protein coding genes. To tackle this issue, we describe a unique short-read custom lncRNA capture sequencing approach that relies on a comprehensive set of 565,878 capture probes for 49,372 human lncRNA genes. This custom lncRNA capture approach was evaluated on various sample types ranging from artificial high-quality RNA mixtures to more challenging formalin-fixed paraffin-embedded tissue and biofluid material. The custom enrichment approach allows the detection of a more diverse repertoire of lncRNAs, with better reproducibility and higher coverage compared to classic total RNA-sequencing.

  Study EGAS00001005418

• An Advanced Molecular Medicine Case Report of a Rare Human Tumor Using Genomics, Pathomics, and Radiomics

  The associated data of this study is derived from a single female patient with pulmonary sclerosing pneumocytoma (PSP). The aim of this study is to provide the most comprehensive, multi-modality sequencing study of a single case of PSP to-date. To this end, the following sequencing experiments were performed: i) RNA-Seq of the primary tumor and adjacent normal tissues (6 replicates for each tissue type), which was intended to analyze RNA-Seq fusions, gene expression, expression mutations, ii) low-pass DNA whole genome sequencing (WGS) from primary tumor tissue and germline, which was intended to analyze copy number aberrations, and iii) DNA targeted panel sequencing of lung cancer associated genes, using primary tumor tissue and germline from white blood cells, which was intended to analyze somatic mutations. Principal findings: i) the PSP hallmark mutation AKT1 (p.E17K) was detected within both the DNA and RNA, and ii) the TP53 signaling pathway was found to be statistically significant by three different pathway analysis tools of analyzing gene expression and pathway ramifications. Among proteins within the TP53 signaling pathway, the p53 inhibitor encoded by MDM2 was found to be overexpressed (by differential gene expression analysis). The original sequencing data (i.e., FastQ files) from each of the aforementioned samples will be accessible through dbGaP.

  Study phs003154

• Single B cell analysis in pemphigus patients

  pemphigus is caused by autoantibodies that target cell-cell adhesion molecules, desmoglein(Dsg). Clinical effect of anti-CD20 antibody therapy suggtests that Dsg-specific memory B cell, the precursor of autoantigen secreting plasmablast, may play an important role of disease activity. This study aimed to isolate Dsg-specific memory B cell using recombinant labeled Dsg proteins and performed single cell RNA-sequence to detect autoimmune B cell specific gene expression. For control, we also isolate non-Dsg specific memory B cells from same patients, or forein antigen (Flu HA) specific memory B cells from vaccinated healthy volunteers.

  Study JGAS000281

• Dac for "Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research"

  This is the DAC for "Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research" of Philipp Koch (philipp.koch@zi-mannheim.de), Frank Winkler (Frank.Winkler@med.uni-heidelberg.de), Moritz Mall( m.mall@dkfz-heidelberg.de)

  Dac EGAC50000000480

• Genome-Wide Association Study of Heparin-Induced Thrombocytopenia

  Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome. Genetic associations were investigated in a cohort of functional assay-confirmed HIT cases, antibody-positive (function assay-negative) controls, and antibody negative controls. Both PF4-specific enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA) were positive in every HIT case. GWAS genotyping was performed at the Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences (IMS). All samples in the discovery and replication cohorts were genotyped using the lllumina® Infinium HumanOmniExpressExome BeadChip, which contains 958,497 markers, including 273,000 functional exonic markers. Quality control was accomplished using sample and marker call rate ≥98%, sex mismatch, duplicate concordance, and removal of related samples through identity by descent. Genomic imputation was performed for samples using Minimac4 and the phase3 v5 reference panel data from the 1000 genomes project. The primary GWAS analysis used multivariable logistic regression assuming an additive genetic model with functional assay-confirmed case status as the outcome. Both PF4/heparin antibody negative and antibody positive controls were considered controls in the primary analysis. Logistic regressions were used to generate odds ratios and 95% confidence intervals (95%CIs) after adjustment for age, sex, and first three principal components.

  Study phs002863

• Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

  Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.

  Dataset EGAD00001002110

• Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging

  In this study we characterised the consequences of DNMT3A- and TET2-mutations in human clonal haematopoiesis. We screened 195 bone marrow samples for mutations by targeted DNA sequencing, and sequenced 99 paired peripheral blood samples to compare mutation detection between bone marrow and blood. We performed single-cell analysis with TARGET-seq+ on 13 samples (4 controls and 9 clonal haematopoiesis samples), which combines single-cell genotyping for targeted mutations with whole transcriptome sequencing on FACS sorted cells. Single-cell genotyping and transcriptomes were sequenced separately and linked by common single-cell identifiers.

  Study EGAS00001007358

• Studies in the Pathogenesis of Systemic Capillary Leak Syndrome (SCLS, Clarkson Disease)

  Systemic capillary leak syndrome (Clarkson disease) is an ultra-rare disease of unknown etiology. Patients experienced transient and recurrent episodes of hypotensive shock and massive peripheral edema due to plasma extravasation, often precipitated by minor viral infections. Disease onset occurs most frequently in middle age, and there is no family history. More than 90% of patients with the disease have monoclonal gammopathy of unknown significance (MGUS). The goal of the study is to determine pathogenic mechanisms and identify genetic underpinnings of the disease. Toward this end, we performed whole genome sequencing (WGS).

  Study phs003261

• GWA Study of Oral Cavity, Pharynx and Larynx Cancers in European, and North and South American Populations - CIDR

  There is striking geographical variation in head and neck cancer (HNC) incidence globally. Some of the highest incidence rates have been observed in Southern and Eastern Europe and South America. The goal of this project is to assess susceptibility loci across and within ancestral backgrounds, using the All of Us array. Ten studies have come together in this initiative.

  Study phs002503

• Induction of HIV-1 Env-Specific Peripheral Blood Plasmablasts and Clonal Persistence as Bone Marrow Plasma Cells Following Vaccination in Humans

  Induction of persistent HIV-1 Envelope (Env) specific antibody (Ab) is a primary goal of HIV vaccine strategies, however, it is unclear if HIV Env immunization in humans induces bone marrow plasma cells, the presumed source of long-lived systemic Ab. To define the features of Env-specific plasma cells after vaccination, samples were obtained from HVTN 105, a phase I trial testing the same gp120 protein immunogen, AIDSVAX B/E, as used in RV144, along with a DNA immunogen in various prime/boost strategies. Boosting regimens that included AIDSVAX B/E induced robust peripheral blood plasmablast responses. The Env-specific immunoglobulin repertoire of the plasmablasts was dominated by VH1 gene usage and targeting of the V3 region. Numerous plasmablast-derived immunoglobulin lineages persisted in the bone marrow greater than eight months after immunization, including in the CD138+ long-lived plasma cell compartment. These findings identify a cellular linkage for the development of sustained Env-specific Ab following vaccination in humans.

  Study phs002027

• Illumina GSA-MD v3 genotyping arrays for 183 samples

  Genotyping arrays for 183 samples from patients with a neuroendocrine tumor of the small intestine. All samples have been hybridized on Illumina GSA-MD v3 arrays with standard automated protocols. Reading of the chips was performed on Illumina iScan+ scanners and this file is the result of primary analysis done using Illumina GenomeStudio software. It contains data for 147 tumors, 2 adenomas, 1 lymph node, 19 mesenteric nodules, 6 liver metastasis and 8 normal ileum samples.

  Dataset EGAD50000000905

• Tam-Seq of HGSOC samples for fixative comparison study

  Targeted amplicon sequencing of samples as part of the study "Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples. The amplicon panel consists of 48 amplicons in TP53, PTEN, EGFR, PIK3CA, KRAS and BRAF genes as described previously [Forshew, STM 2012]. All libraries were pooled and quantify using DNA 1000 kit on Agilent 2100 Bioanalyzer and KAPA SYBR FAST ABI Prism qPCR Kit (KAPA Biosystems) on 7900HT Fast Real-Time PCR System (Applied Biosystems) according to the supplier's recommendations. Reads were aligned using bwa-mem v0.7.12-r1039 to the 1000 genomes version of human genome build GRCh37, retaining duplicate reads.

  Dataset EGAD00001001937

• Chracterising cellur pathways underlying CD3/CD28 activation of human CD4+ cells

  We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Sorted Tcons were activated using a titration of anti-CD3 and anti-CD28 in combination as well as individually. As a control we cultured cells in the same conditions but without the stimuli. In total, we defined seven conditions from four individuals for sequencing. 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 EGAD00001006610

• Chracterising cellur pathways underlying CD3/CD28 activation of human CD4+ cells

  We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Sorted Tcons were activated using a titration of anti-CD3 and anti-CD28 in combination as well as individually. As a control we cultured cells in the same conditions but without the stimuli. In total, we defined seven conditions from four individuals for sequencing. 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 EGAD00001006612

• Warm_Autopsy_Single_Cell_X10

  Study of cell lineage and embryogenesis using biopsy samples from sites across the whole body (post mortem). Sample donors are recruited sensitively through the Phoenix study and consent to samples being taken after their death for both the Phoenix study and this WTSI study.

  Dataset EGAD00001003240

• Single-cell RNA-sequencing of H3-K27M diffuse midline glioma.

  Fastq files are deposited for single-cell transcriptomes of patient H3-K27M diffuse midline gliomas, generated using the SMART-seq2 method.

  Dataset EGAD00001011339

• RNA-seq BAM files from newborn screening dried blood spot samples

  Paired-end RNA-seq BAM files from 21 newborn screening dried blood spot (DBS) samples. These DBS samples were obtained from extremely low gestional age newborns, where 10 of them were affected by a fetal inflammatory response (FIR) before birth, and 11 were unaffected. Total RNA was sequenced using an Illumina NextSeq-500 instrument. The sample preparation protocol included the depletion of rRNA and globin mRNA using the Globin Zero Gold rRNA Removal Kit from Illumina. Libraries were prepared using the NebNext Ultra TM II Directionl RNA LIbrary Prep Kit (New England Biolabs). There is one BAM file per sample and there is an additional BAM file, corresponding to sample BS13, which was downsampled to 1/4 of its original depth (see BS13_README file for details).

  Dataset EGAD00001005009

• Genetic Epidemiology Network of Arteriopathy (GENOA)

  The Genetic Epidemiology Network of Arteriopathy (GENOA): GENOA is one of four research networks that form the NHLBI Family Blood Pressure Program (FBPP). From its inception in 1995, GENOA's long-term objective was to elucidate the genetics of hypertension and its arteriosclerotic target-organ damage, including both atherosclerotic (macrovascular) and arteriolosclerotic (microvascular) complications involving the heart, brain, kidneys, and peripheral arteries. Two GENOA cohorts were originally ascertained (1995-2000) through sibships in which at least 2 siblings had essential hypertension diagnosed prior to age 60 years. All siblings in the sibship were invited to participate, both normotensive and hypertensive. These include non-Hispanic White Americans from Rochester, MN (n =1583 at the 1st exam) and African Americans from Jackson, MS (N=1854 at the 1st exam). During the second exam (2000-2005), approximately 80% of participants were re-recruited. The GENOA data consists of biological samples (DNA, serum, urine) as well as demographic, anthropometric, environmental, clinical, biochemical, physiological, and genetic data for understanding the genetic predictors of diseases of the heart, brain, kidney, and peripheral arteries. Family Blood Pressure Program (FBPP): GENOA's parent program, the FBPP, is an unprecedented collaboration to identify genes influencing blood pressure (BP) levels, hypertension, and its target-organ damage. This program has conducted over 21,000 physical examinations, assembled a shared database of several hundred BP and hypertension-related phenotypic measurements, completed genome-wide linkage analyses for BP, hypertension, and hypertension associated risk factors and complications, and published over 130 manuscripts on program findings. The FBPP emerged from what was initially funded as four independent networks of investigators (HyperGEN, GenNet, SAPPHIRe and GENOA) competing to identify genetic determinants of hypertension in multiple ethnic groups. Realizing the greater likelihood of success through collaboration, the investigators began working together during the first funding cycle (1995-2000) and formalized this arrangement in the second cycle (2000-2005), creating a single confederation with program-wide and network-specific goals.

  Study phs000379

• CAF-S3 subset in human breast and ovarian cancers

  Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. By combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast and ovarian cancers.

  Study EGAS00001003344

• Whole-genome sequencing of paired tumor and blood samples from 65 bladder cancer patients

  65 paired tumor and normal whole-genome sequencing samples from urothelial bladder carcinomas (UBC, the most common type of bladder cancer) are used to uncover the whole-genome mutational landscape of UBC. Recurrent mutations in noncoding regions affecting gene regulatory elements and structural variations leading to gene disruptions are prevalent in this type of cancer.

  Dataset EGAD00001004545

• Alopecia and Vitiligo

  exome sequencing data captured with agilent v4 (71k) and sequenced on illumina technology. data from a total of 40 samples, of which 14 are vitiligo cases with familial history of vitiligo or immune disease, and the remaining are alopecia areata cases.

  Dataset EGAD00001005289

• APOBEC3 mutagenesis drives therapy resistance in breast cancer

  Acquired genetic alterations commonly drive resistance to endocrine and targeted therapies in metastatic breast cancer, however the underlying processes engendering these diverse alterations are largely uncharacterized. To identify the mutational processes operant in breast cancer and their impact on clinical outcomes, we utilized a well-annotated cohort of 3,880 patient samples with paired tumor-normal sequencing data. The mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were highly prevalent and enriched in post-treatment compared to treatment-naïve hormone receptor-positive (HR+) cancers. APOBEC3 mutational signatures were independently associated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor combination therapy in patients with HR+ metastatic breast cancer. Whole genome sequencing (WGS) of breast cancer models and selected paired primary-metastatic samples demonstrated that active APOBEC3 mutagenesis promoted resistance to both endocrine and targeted therapies through characteristic alterations such as RB1 loss-of-function mutations. Evidence of APOBEC3 activity in pre-treatment samples illustrated a pervasive role for this mutational process in breast cancer evolution. The study reveals APOBEC3 mutagenesis to be a frequent mediator of therapy resistance in breast cancer and highlights its potential as a biomarker and target for overcoming resistance.

  Study EGAS50000000875

• GeneScreen, a Population Based, Targeted Genomic Screening Study

  The GeneScreen research study was based at the University of North Carolina (UNC) at Chapel Hill. It brought together researchers from different disciplines, including genetics, clinical medicine, bioethics, sociology, anthropology, psychology, and public health, to study the best ways to offer targeted genetic screening to the general adult population. DNA samples were collected from people who joined GeneScreen to look at a targeted panel of 17 genes. It tested for genetic differences (called mutations) that can cause one of 11 rare, but preventable or treatable conditions, including certain types of cancer and heart disease. Each condition has specific medical advice people can follow with their doctors to prevent or treat a serious health problem. The GeneScreen study was approved by the UNC Institutional Review Board and by the Kaiser Permanente Center for Health Research Institutional Review Board. GeneScreen is funded by the National Human Genome Research Institute of the National Institutes of Health.

  Study phs001817

• International Cancer Proteogenome Consortium (ICPC): Proteogenomics of Early Stage Lung Adenocarcinoma in Taiwan

  Lung cancer in East Asia is characterized by a high percentage of never-smokers with early-onset adenocarcinoma, predominantly with EGFR mutations. To provide an insight into the molecular phenotype of this demographically distinct disease, we have performed a proteogenomics study on a prospectively collected cohort representing early stage lung adenocarcinoma in Taiwan. The distinct mutational profile revealed a high prevalence of the APOBEC mutational signature in early-onset females, implicating differential regulation of APOBEC enzymes and DNA damage pathways, as well as enrichment of mutational signatures congruent with environmental carcinogens over-represented in the genomic location of EGFR. We delineate the proteogenomic hallmarks of tumor progression and propose a proteomics-informed classification that resolves the EGFR mutation heterogeneity associated with survival within the early stages. Functional annotation of the molecular subtypes by protein network analysis highlights candidate biomarkers for patient stratification. Our integrative analysis reveals the molecular architecture of lung cancer in East Asia and enables the path for precision medicine.

  Study phs001954

• Genome-wide Rare Variant Score Associates With Morphological Subtypes of Autism Spectrum Disorder

  Defining different genetic subtypes of Autism Spectrum Disorder (ASD) can help predict developmental outcomes. Based on minor physical and major congenital anomalies, we categorized 325 Canadian children with ASD into dysmorphic and non-dysmorphic subgroupings. We developed a method to calculate a genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data for each ASD proband. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD had a significantly higher GRVS compared to those with non-dysmorphic ASD (P= 0.027). Using the polygenic transmission disequilibrium test, we observed an over-transmission of ASD-associated common variants in non-dysmorphic ASD probands (P= 2.9×10-3). We replicated our findings using 442 ASD probands that had accompanying morphology data in the Simons Simplex Collection. Our findings provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.

  Study EGAS00001005753

• Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay

  Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening. To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay. Cell-free DNA (cfDNA) samples from the blood plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, ten advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer.

  Dataset EGAD50000000679

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Emory Cohort

  The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases. This study contains variant calls derived from the whole genome sequence data of an early-onset coronary artery disease case-control cohort selected from Emory University Cardiovascular Biobank. Case status was assigned based on the presence of myocardial infarction, coronary artery stenosis greater than 70% in at least one coronary artery, and/or revascularization (coronary angioplasty with or without stent placement or coronary artery bypass grafting) at an early age. For these samples "early age" is defined as men 60 years of age or younger and women 70 years of age or younger. The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases.

  Study phs001880

• TIRE-seq_PDN

  TIRE-seq is a novel RNA sequencing method that integrates mRNA purification directly into library preparation, eliminating separate RNA extraction. The technique demonstrated utility across three biological applications, including capturing transcriptional changes in human T cells, identifying genes driving murine dendritic cell differentiation, and analyzing the dose-response effects of temozolomide on patient-derived neurospheres. With its simplified approach and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies.

  Dataset EGAD50000001261

• snRNA sequencing of high-grade pancreatic neuroendocrine carcinoma (panNEC)

  High-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two interesting neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.

  Dataset EGAD00001016154

• The evolutionary landscape of colorectal tumorigenesis

  The genetic events that cause colorectal adenomas to progress to carcinomas remain largely undetermined. Using multi-region genome/exome sequencing of 24 benign and malignant colorectal tumours, we probe the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations, hence lack selective sweeps, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas not by nucleotide-level mutations (drivers or burden), but by widespread aneusomies that are usually clonal and often accrue in a “punctuated” fashion. Adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilising selection.

  Study EGAS00001003066

• Acral Melanoma PDXs from the admixed Brazilian Population - filtered PDX sample BAM files - RNAseq

  BAM files containing the whole exome data for the Patient Derived Xenograft samples mapped to build GRCh38. All files have been processed with XenofilteR to remove mouse reads. Acral melanoma (AM) is an aggressive melanoma subtype with limited therapeutic options and poor outcomes. In non-European descent and admixed populations, like in Latin America, it can account for a significant proportion of cutaneous melanoma cases. Here, we performed comprehensive genomic and functional profiling of AM from a uniquely diverse Brazilian cohort. Whole-exome and transcriptome sequencing was performed on both tumours and patient-derived xenograft (PDX) samples. The PDX were obtained from a comprehensive collection of patient-derived xenograft (AM-PDX) models that we established which faithfully retained the histopathological and genomic features of the original tumours.

  Dataset EGAD00001015746

• Acral Melanoma PDXs from the admixed Brazilian Population - filtered PDX sample BAM files - Whole exome sequencing data

  BAM files containing the whole exome data for the Patient Derived Xenograft samples mapped to build GRCh38. All files have been processed with XenofilteR to remove mouse reads. Acral melanoma (AM) is an aggressive melanoma subtype with limited therapeutic options and poor outcomes. In non-European descent and admixed populations, like in Latin America, it can account for a significant proportion of cutaneous melanoma cases. Here, we performed comprehensive genomic and functional profiling of AM from a uniquely diverse Brazilian cohort. Whole-exome and transcriptome sequencing was performed on both tumours and patient-derived xenograft (PDX) samples. The PDX were obtained from a comprehensive collection of patient-derived xenograft (AM-PDX) models that we established which faithfully retained the histopathological and genomic features of the original tumours.

  Dataset EGAD00001015748