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• Circulating tumour DNA abundance and potential utility in de novo metastatic prostate cancer

  We set out to determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. We collected and sequenced 77 plasma cell-free DNA samples from 53 newly diagnosed patients with mCSPC. Targeted sequencing was also performed on DNA from 48 diagnostic prostate tissue samples.

  Dataset EGAD00001004526

• 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

• PROP1_study

  The dataset for the PROP1 study consists of samples of patients with combined pituitary hormone deficiency due to two most prevalent mutations in the PROP1 gene (c.301_302delGA and c.150delA) and healthy relatives and controls. All subjects were genotyped for 21 single nucleotide polymorphisms surrounding the PROP1 gene in order to assess the potential ancestral origin of the respective mutations. The genotype data are displayed in the vcf format.

  Dataset EGAD00001001303

• Deep sequencing of 60 genes from BCP HD ALL samples on Illumina HiSeq 2000, 100 bp paired-end

  50 ng of genomic double stranded DNA was enzymatically sheared to an average size of 200 bp. Further processing was performed using Illumina Nextera Rapid Capture Custom Kit (Illumina) and 100 bp paired-end sequencing was performed with 24 samples per lane on a Illumina HiSeq 2000 (Illumina) to reach a coverage of 100-1000x.

  Dataset EGAD00001002652

• Bulk RNA sequencing data in "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2"

  This dataset includes 14 bulk RNA sequencing data (28 fastq files) in the study entitled "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2". RNA sequencing library was generated with Truseq stranded total RNA Gold kit.

  Dataset EGAD00001006241

• Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

  RNA sequencing data from breast cancers (n=18) and their matched HN tissues (n=36), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised proximal to (TP, less than 2 cm) and distal from (TD, 5-10 cm) the primary tumor.

  Dataset EGAD00001006291

• Whole genome sequencing of adult glioblastoma nuclei

  Three primary adult glioblastoma specimens were dissociated and nuclei were extracted. A portion of the nuclei was used for single-cell ATAC seq and the remainder were submitted for whole genome sequencing, to provide orthogonal validation of copy number variations in the samples compared to single-cell ATAC seq. Samples were sequenced on the Illumina NovaSeq 6000 in paired-end mode.

  Dataset EGAD00001007651

• Acute myeloid leukemia bulk RNA-seq (Diagnosis and Relapse)

  To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. All the samples are bone marrow aspirates.

  Dataset EGAD00001008374

• Single cell atlas of human glioma

  We profiled 87 primary-recurrentpatient-matched paired GBM specimens with single-nucleus RNA and bulk-DNA sequencing and single-cell open-chromatin and spatial transcriptomics/proteomics assays. We found that recurrent GBMs are characterized by a shift to a mesenchymal phenotype in response to therapy

  Dataset EGAD00001008811

• Healthy Never Smokers

  Bronchial brushing dataset from healthy never-smokers after exposure to diesel exhaust. Include 18 samples from 9 research participants who underwent bronchoscopy after controlled exposure to diesel exhaust. Main study design described in detail in Ryu et al 2022 AJRCCM (PMID: 35202552). This dataset was used in Hill et al Nature 2023.

  Dataset EGAD00001010024

• Ultra-fast deep-learned pediatric CNS tumor classification.

  In this study nanopore sequencing was applied to obtain sparse DNA methylation profiles from pediatric CNS tumor samples. A neural network was used to classify the tumor based on the obtained methylation profile.

  Dataset EGAD00001011303

• PacBio Rare Disease Study

  This study leverages PacBio HiFi long-read sequencing technology to comprehensively analyze the genomic architecture of rare diseases. By generating highly accurate, long-read sequences, we aim to resolve complex structural variants, repeat expansions, and other genomic features that are often missed by short-read sequencing. Our approach facilitates improved variant detection and interpretation, advancing the understanding of rare disease etiology and enabling more precise genetic diagnoses.

  Dataset EGAD00001015611

• scRNA-seq dataset to study interactions between HSPCs, BMSCs and immune microenvironment

  Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, we provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human MDS.

  Dataset EGAD00001015770

• RNA-Seq dataset of Targeting the dark proteome to expand the lineage-retained antigen landscape in neuroblastoma

  RNA-Seq dataset of Targeting the dark proteome to expand the lineage-retained antigen landscape in neuroblastoma

  Dataset EGAD00001016124

• Genetic Diseases of Immune Homeostasis and Autoimmunity Caused by GIMAP Deficiency

  We investigated 17 affected individuals in 9 kindreds with lymphopenia, splenomegaly, liver disease, thrombocytopenia, lymphadenopathy, severe recurrent lung infections, skin diseases, and lymphoma. Whole-exome sequencing of the cohort revealed mutations in GIMAP5. We also found another patient from one kindred with a unique mutation in the gene GIMAP6, discovered by whole-exome sequencing. A comprehensive investigation of this gene mutation through in vivo and in vitro experiments revealed that GIMAP6 deficiency results in defects in autophagy in patient T cells and interruption of GIMAP7 and GABARAPL2 interactions. GIMAP6 deficiency leads to affected patients to present with clinical phenotypes such as recurrent infections, lymphoproliferation, autoimmunity, and inflammation.

  Study phs002816

• Expressed Pseudogenes in the Transcriptional Landscape of Human Cancers

  In this study, we describe a systematic analysis of pseudogene 'transcription' from an RNA-Seq resource of 293 samples, from 13 cancer and normal tissue types. We observed a highly prevalent, genome-wide expression of pseudogenes that could be categorized as universally expressed or lineage- and/or cancer-specific. We also explored disease subtype specificity and functions of selected expressed pseudogenes. We provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.

  Study phs000525

• Gene Expression in an African American Schizophrenia Dataset

  Schizophrenia is a common and severe psychotic disorder. While some common SNPs and rare copy number variants have been identified as being significantly associated with disease risk, the biological mechanisms remain largely undefined. To identify gene expression abnormalities in schizophrenia, we generated whole-genome gene expression profiles using RNAseq on lymphoblastoid cell lines from schizophrenia cases and controls of African American ancestry. Genes related to immune processes were enriched in the genes differentially expressed in the schizophrenia cases. Approximately half of the differentially expressed genes in this African American dataset were also differentially expressed by affection status in our previously studied European ancestry dataset (PMID: 28418402).

  Study phs002842

• FaceBase Study of Facial Shape in Tanzania: CIDR

  The goals of this project are to identify loci that underlie major genetic determinants of orofacial shape, by means of a GWAS in a cohort of normal African children (from Tanzania) from whom we have collected 3D digitized facial morphometric scans, and a subsequent replication study of normal children from the same population. These studies are part of the NIDCR FaceBase initiative (https://www.facebase.org/). In addition to dbGaP, all study genotype and phenotype data (including primary facial scans and landmarks) will be available for data-sharing with qualified investigators via the NIDCR FaceBase Hub (www.facebase.org/), following approval by the NIDCR FaceBase Data Access Committee.

  Study phs000622

• Whole Exome Sequences of Human Embryonic Stem Cell Lines

  Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole exomes of widely available hESCs. The data generated has provided new insights about the nature of acquired variation and the genomic integrity of the cell lines. We anticipate that this online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease and trait-associated genetic variants.

  Study phs001343

• NHLBI TOPMed - NHGRI CCDG: Massachusetts General Hospital (MGH) Atrial Fibrillation Study

  The Massachusetts General Hospital (MGH) Atrial Fibrillation Study was initiated in 2001. The study has enrolled serial probands, unaffected and affected family members with atrial fibrillation. At enrollment participants undergo a structured interview to systematically capture their past medical history, AF treatments, and family history. An electrocardiogram is performed; the results of an echocardiogram are obtained; and blood samples are obtained. For the TOPMed WGS project only early-onset atrial fibrillation cases were sequenced. Early-onset atrial fibrillation was defined as an age of onset prior to 66 years of age. Comprehensive phenotypic and pedigree data for study participants are available through dbGaP phs001001.

  Study phs001062

• Whole Exome Sequencing of Colorectal Cancer Patients from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)

  Colorectal cancer is a molecularly heterogeneous disease. Whole Exome Sequencing from patients diagnosed with colorectal cancer in the NHS and HPFS cohorts will extend our understanding of the genetic changes occurring in specific clinical contexts in the disease. This effort has the potential to discover novel recurrently mutated genes and pathways in colorectal cancer that can be functionally validated and give further insights to colorectal cancer pathogenesis. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 and sequencing was performed on an Illumina HiSeq 2000.

  Study phs000722

• Single Cell RNA-Sequencing in Adenoid Cystic Carcinoma

  This study of salivary adenoid cystic carcinoma aimed to profile individual malignant and stromal cells in treatment-naive head and neck adenoid cystic carcinoma, with or without metastatic cervical lymph nodes. Clinical and pathologic information was collected on all patients, in addition to a fresh biopsy sample from the primary tumor and/or metastatic lymph node at the time of initial surgery. A fresh biopsy sample from a matched local recurrence was also collected for a single unique patient. Biopsy specimens were processed for single cell RNA-seq. A total of ~1,700 single cells from seven participants were included in the final dataset.

  Study phs003070

• Linked Read Sequencing of Gastric Cancer Metastases for Complex SV Resolution

  In this study, linked read sequencing was performed on two ovarian metastases and matched normal tissue, from a patient with primary diffuse gastric cancer. Linked read sequencing is a DNA preparation technology whereby high molecular weight molecules of DNA are uniquely barcoded prior to fragmentation and sequencing, thus retaining information about genomic contiguity. This study performed an extended analysis of linked read sequencing data to resolve the complex structures of structural variants in the cancer genomes. Complex structural rearrangements were identified in the genomic region surrounding the known oncogene FGFR2, and the association between FGFR2 and gastric cancer metastasis was demonstrated in an organoid model.

  Study phs001362

• Genetics of Male Infertility Initiative (GEMINI)

  The Genetics of Male Infertility Initiative (GEMINI) project is a multi-center study designed to discover and characterize genetic variants conferring risk for male infertility. Patients enrolled in GEMINI have been clinically diagnosed with male infertility. Patients are recruited from multiple medical centers and are primarily of European ancestry. DNA from each patient is extracted from peripheral blood or saliva and used for exome sequencing. Genetic data generated by the GEMINI project has contributed to the discovery of over a dozen genes involved in human infertility. A VCF file of genetic data from GEMINI patients that have been appropriately consented will be available through dbGaP.

  Study phs003115

• Comprehensive Analysis of the Immunogenomics of Triple Negative Breast Cancer Brain Metastases from LCCC1419

  Triple negative breast cancer (TNBC) is an aggressive subset of breast cancer that lacks expression of the estrogen and progesterone receptors (ER and PR) and HER2. Nearly 50% of patients with advanced TNBC will develop brain metastases (BrM), commonly with progressive extracranial disease. Immunotherapy has shown promise in the treatment of advanced TNBC; however, the immunogenomics of BrM remains largely unknown. Thus, we conducted a comprehensive analysis of TNBC BrM and matched primary tumors to characterize the genomic and immune landscape of TNBC BrM to foster the development of immunotherapy strategies in this aggressive and clinically unmet disease.  

  Study phs002457

• DNA methylation in rhabdomyosarcoma PDX and PDX-derived primary cells

  Conditions to maintain primary tumor cells in culture are largely unknown for most tumor entities including rhabdomyosarcoma. In this collaborative study with Dr. Beat Schäfer's laboratory, we performed DNA methylation profiles of rhabdomyosarcoma patient-derived xenograft (PDX) and their matching PDX-derived primary cells (PPC), where the PPCs were developed and maintained under optimized culture conditions. We further compared DNA methylation profiles between these PDXs and PPCs. Exome sequencing and copy number analysis between these rhabdomyosarcoma PDXs and PPXs were also carried out. These analyses may help us to evaluate a feasibility of in vitro profiling of primary rhabdomyosarcoma cells from a genomic perspective.

  Study phs002051

• Copy Number Variation in Congenital Kidney Malformations

  We report a study of large rare, copy number variants (CNVs) in 192 patients with renal hypodysplasia (RHD). Congenital malformations of the kidney and urinary tract are present in 3 to 7 per 1,000 births, accounting for 16% of birth defects. These malformations account for 40-50% of pediatric and 7% of adult end-stage renal disease worldwide. Among these malformations, RHD represents a severe forms of disease with profound impact on long-term renal survival. We found that a significant fraction of RHD patients have a molecular diagnosis attributable to a genomic disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances.

  Study phs000565

• Spatiotemporal Transcriptome of the Human Brain

  Comprehensive knowledge about the spatiotemporal dynamics of the brain transcriptome is essential for a better understanding of neurodevelopment, sexual dimorphism, and evolution, as well as our increased susceptibility to certain brain disorders. We generated and analyzed genome-wide exon-level transcriptome data from 16 brain regions of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genome-wide genotyping of 2.5 million SNPs and assessed genome normality for all donors. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.

  Study phs000406

• DNA Methylation age and mortality in the Lothian Birth Cohorts of 1921 and 1936

  The study examined the association between DNA methylation age and mortality. Methylation age was estimated in 4 cohorts (including the Lothian Birth Cohorts of 1921 and 1936) and related to subsequent time-to-death. Across all four cohorts there was a strong correlation between predicted methylation age and chronological age. For individuals with a 5 year age acceleration (DNA methylation age - chronological age = 5), there was a meta analysed hazard ratio of mortality of 1.21 [1.14, 1.29]. Phenotype data associated with the study are available through dbGaP, the methylation raw data are available through the European Genome-phenome Archive (EGA; accession number EGAS00001000910).

  Study phs000821

• STAMPEED: Myocardial Infarction Genetics Consortium (MIGen)

  Myocardial infarction (MI) is a common complex disease and the leading cause of death and disability worldwide. The genetic basis of this disease is largely unknown. It has been thought that early-onset MI events would have a substantially greater heritability, thus making DNA collections with younger individuals desirable. More recently, genome-wide association studies have become feasible through the development of whole genome arrays and a large catalogue of common variants reported in the International HapMap database. This study aims to use Affymetrix genotyping platform to do a whole genome scan in 3000 early-onset MI cases and 3000 matched controls from 6 study collection sites.

  Study phs000294

• Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

  Neurodevelopmental Disorders (NDDs) are a group of disorders that typically manifest early in development and may give rise to impaired cognition, communication, adaptive behavior, and psychomotor skills. This study aims to take a more comprehensive view into the genomic landscape of structural variants implicated in NDDs with intellectual disability (ID). We have evaluated the genome of families with a genetically unsolved severe NDD via optical genome mapping. This study identified likely pathogenic or pathogenic structural variants in known NDD genes, including BCL11A, OPHN1, PHF8, SON, and NFIA. Data is available in VCF format, following the standard filtering settings in Bionano Access and available as "variants_combine_filters_inMoleRefine1.vcf" files.

  Study phs002937

• My Pediatric and Adult Rare Tumor (MyPART) Natural History Study of Rare Solid Tumors

  The goal of this study is to comprehensively and longitudinally evaluate the natural history of patients with rare solid tumors or tumor predisposition syndromes, estimating and defining their clinical spectrum (e.g. disease course and survival). Clinical data, patient reported outcomes (PROs), and biospecimen associated data are collected. Clinical data includes response to treatment, tumor pathology, and imaging. PROs include measures of pain, depression, anxiety, mobility, and cognitive functioning. Biospecimen data includes next-generation sequencing [RNAseq, whole exome sequencing (WES), whole genome sequencing (WGS), EPIC methylation array data, and TruSight Oncology 500 gene panel sequencing], cytokine analysis of plasma, immune phenotyping of circulating peripheral blood mononuclear cells.

  Study phs003143

• NHLBI TOPMed: Childhood Asthma Management Program (CAMP)

  The Childhood Asthma Management Program (CAMP) was designed to evaluate whether continuous, long-term treatment (over a period of four to six years) with either an inhaled corticosteroid (budesonide) or an inhaled noncorticosteroid drug (nedocromil) safely produces an improvement in lung growth as compared with treatment for symptoms only (with albuterol and, if necessary, prednisone, administered as needed). The primary outcome in the study was lung growth, as assessed by the change in forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. Secondary outcomes included the degree of airway responsiveness, morbidity, physical growth, and psychological development.

  Study phs001726

• Chromothripsis in Small Cell Lung Carcinoma Associated with Carcinoid Transformation

  Small cell lung carcinoma (SCLC) is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. We performed detailed clinicopathologic, genomic, and transcriptomic profiling of an atypical subset of SCLC in never/light smokers that lacked RB1 and TP53 co-inactivation and found that most cases were associated with chromothripsis – massive, localized chromosome shattering, recurrently involving chromosomes 11 or 12, among other findings. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids. Conversely, SCLC never smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never smokers.

  Study phs003676

• Radiation-Related Genomic Profile of Papillary Thyroid Cancer after the Chernobyl Accident

  The April 26, 1986 accident at the Chernobyl nuclear power plant in northern Ukraine resulted in the release of radioactive contaminants, which were deposited in the surrounding areas in Ukraine, Belarus, and Russia. The main radiation-related health effect resulting from these exposures is the increased occurrence of thyroid cancer among individuals who were children at the time of the accident or born shortly thereafter. The purpose of this study was to conduct a comprehensive genomic landscape analysis of papillary thyroid tumors arising in individuals who were exposed as children to radioactive iodine (I-131) from the Chernobyl nuclear power plant accident.

  Study phs001134

• Genetic Analysis of Epidermal Inclusion Cysts

  The goal of this study was to identify a potential driver of epidermal inclusion cysts, or epidermoid cysts, (EICs) in human skin. Individuals were recruited at EIC excision appointments made a priori, with no exclusion criteria. Fresh biopsies and saliva were taken from consented patients, and DNA harvested immediately. Whole exome sequencing was performed (150-bp paired end reads) to 200X in tissue and 80X in saliva via Illumina NovaSeq 6000 sequencer. Identification of somatic mutations was performed using GATK best practices. Somatic variants in the NEK9 gene were found in 12/14 cases sequenced, with clustering of variants within the RCC1 and kinase domains of the protein.

  Study phs003776

• Single-Cell Transcriptomic Characterization of Microscopic Colitis

  Patients with microscopic colitis (MC), chronic diarrhea without histological signs of MC, or unaffected controls were profiled using single-cell RNA sequencing (scRNA-seq; inDrops and 10X Genomics were used). One profiled patient without clinical symptoms was found to have histological signs of MC (asymptomatic MC). Some of the subjects from dbGaP study phs003418 are controls in this study. T-Cell Receptor sequencing (TCR-Seq) was also performed on a subset of patients. Individual transcriptomes were analyzed to characterize the cellular profile associated with MC and search for mediators of disease pathology. Raw reads and processed count matrices will be available through dbGaP.

  Study phs003876

• HuBMAP: High Resolution 3D Mapping of Cellular Heterogeneity Within Multiple Types of Mineralized Tissues

  The overall goal of the study was to generate 3D single cell maps of healthy human knee cartilage. Articular cartilage from the weightbearing and non-weightbearing regions of the femoral condyles in healthy knees from young donors (n=12) was analyzed by bulk RNA-sequencing (RNA-Seq), single nuclei RNA (snRNA-seq) and ATAC-sequencing and by spatial transcriptomic methods (GeoMx, MERFISH and Xenium). These multimodal data and additional single cell RNA-sequencing (scRNA-seq) data were integrated to generate a comprehensive molecular, genomic and function annotation of chondrocyte populations. Regulatory mechanisms were derived by linking motifs in expressed genes, transcription factors and chromatin organization.

  Study phs003721

• Vitamin-D-Kids Asthma

  The Vitamin D Kids Asthma Study (VDKA) was a 48-week multicenter randomized, double-blinded, placebo-controlled trial of vitamin D3 for severe asthma exacerbations in children 6-16 years old, recruited from February 28, 2016 to September 20, 2019. An ancillary study for nasal sampling was conducted at the Pittsburgh site. Prior to randomization, participants completed questionnaires and underwent collection of nasal samples for gene expression studies. VDKA was approved by the IRBs of all participating institutions, and the ancillary study was approved by the IRB of the University of Pittsburgh. Written parental consent was obtained for participating children, from whom written assent was also obtained.

  Study phs004051

• Amplicon sequencing of melanoma samples

  The types of biomarkers for skin tumors have been 1) biochemical markers in blood, urine, and body fluid, 2) histopathological markers, 3) genetic examination of tumor tissue, 4) tumor-susceptibility assessed by germ_x0002_line genetic examination. Biomarkers in a blood are frequently used in the treatment of cutaneous malignancies, but are not suitable for early detection of malignancies. Research on circulating tumor cells, cell free DNA, exosomes has been promoted in recent years, but clinical application is halfway. Based on these circumstances, the purpose of this study is to search for biomarkers for diagnosis, therapeutic effect, and follow-up of skin tumors, and to verify their usefulness.

  Study JGAS000351

• Genetic mutation profiling of lymphomas arising in the uterine cervix and vagina

  Follicle center lymphoma (FCL) of the lower female genital tract (LFGT) is a rare lymphoma, with fewer than 20 cases reported to date. Since the genetic features of FCL of the LFGT have not been well characterized, we aimed to identify genetic alterations in this tumor through whole-exome sequencing or targeted gene panel analysis. Genomic DNA was extracted from a frozen tissue sample obtained from a surgically resected uterine cervical tumor. Whole-exome sequencing was performed using the Illumina NovaSeq X Plus platform. Library preparation was conducted with the SureSelect Human All Exon V6 kit, and sequencing was carried out with 150 bp paired-end reads.

  Study JGAS000823

• Development of hunanized mice for human hematopoisis and immunity research

  We obtained peripheral blood or bone marrow samples from 112 acute myeloid leukemia patients and examined sensitivity and resistance of the AML samples to molecular targeting drugs. By doing RNA sequencing using AML cells, we found heterogenous gene expression patterns in AML with different mutational landscapes. From the RNA sequencing, we identified anti-apoptosis, cell cycle progression, and immune-related signals as pathways up-regulated in AML cells as compared with normal CD34+ cells. From the pathway analyses, we further setup in vitro experiments to find vulnerability genes in clinically-aggressive AML. BIRC, BCL2, MCL1, AURKB, and KIF10 may be essential molecules for AML cell survival and proliferation.

  Study JGAS000253

• North American Brain Expression Consortium (NABEC) Exome Sequencing

  A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on expression profile. We find an abundance of genetic cis regulation mRNA expression. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.

  Study EGAS00001002110

• Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks

  The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying ‘personal’ gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genome of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers.

  Study EGAS00001002571

• Diversity of U1 small nuclear RNAs and Evaluation of Diagnostic Methods for their Mutations

  U1 small nuclear RNA (snRNA) mutations are recurrent non-coding alterations found in various malignancies, including medulloblastoma, yet their identification has proven challenging due to their repetitive nature. To establish a robust DNA-based, and RNA-based method for detecting U1 snRNA mutations, we performed targeted DNA sequencing using our original gene panel for medulloblastoma and RNA-sequencing. As an RNA-based method, we developed a random forest classifier employing splicing patterns which were massively altered as a result of U1 snRNA mutations. By using both methods, we successfully detected U1 snRNA mutation in five DNA samples and four RNA samples.

  Study EGAS50000000693

• 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/

  Study EGAS00001004147

• Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden

  Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we developed a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions was strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients.

  Study EGAS00001004657

• Comprehensive Deep Sequencing Atlas in HCC tumors

  Establishment of a comprehensive deep sequencing atlas focused on Hepatocellular Carcinoma (HCC) tumors, employing Whole Genome Sequencing (WGS), RNA Sequencing (RNAseq), and Whole Exome Sequencing (WES). The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with this liver cancer. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.

  Study EGAS00001007694

• Targeted sequencing of follicular lymphoma tumour samples from the UK's Haematological Malignancy Research Network

  Follicular lymphoma displays morphological and clinical heterogeneity, underpinned by shared molecular pathogenesis. Mutations in epigenetic regulators alongside t(14;18) have been identified as disease initiating events. Additional mutational diversity suggests disease heterogeneity. Whether this resolves into mechanistically distinct subsets remains an open question. Targeted sequencing was applied to an unselected population-based FL cohort (n=548) diagnosed in a catchment population of ~4 million (14 centers), with full clinical follow-up (n=538) that included 96 DLBCL transformations. We investigated whether molecular subclusters of FL can be identified, and whether mutational data provide predictive information relating to transformation.

  Study EGAS00001005238

• 2014_Lung_sq_WES

  Purpose Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to lack of systematic understanding of the molecular parthenogenesis of the disease. To identify therapeutic targets and comparatively analyze them in lung SqCC, we probed somatic alterations of Korean lung SqCC. Patients and Methods We performed massively parallel whole-exome sequencing of 104 Korean lung SqCC patients’ samples with matched normal samples. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.

  Study EGAS00001002844