16792 results for "sec+and+unspecified+malignant+neoplasm"

in 65.44 milliseconds.

• RNA-Seq of human longitudinal whole blood samples from PCR-positive and PCR-negative recent household contacts of COVID-19 index cases.

  Little is known about the transcriptomic profile of individuals who are exposed to SARS-CoV-2 yet resist becoming PCR positive. To investigate this, longitudinal whole-blood samples were taken (0, 7, 14, and 28 days after enrolment) from PCR positive and PCR negative SARS-CoV-2-naïve household contacts who were recently exposed to a COVID-19 index. Samples were also taken from pre- and post-pandemic unexposed controls. Total RNA was extracted from PAXgene tubes before undergoing poly(A) selection followed by 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 across 2 flowcells of an Illumina HiSeq 4000.

  Dataset EGAD50000000684

• Single-cell RNA sequencing of pediatric Hodgkin Lymphoma to study the inhibition of T cell subtypes

  Here, we applied single-cell RNA-sequencing (scRNA-seq) on isolated HRS cells and the immune cells from the same pediatric classical Hodgkin Lymphoma (cHL) tumors. Specifically, 13 cHL patients and 3 reactive lymph node control samples were included in this cohort. This allowed us to identify genes of cell surface proteins that are consistently overexpressed in HRS cells and can potentially be used as targets for antibody-drug conjugates or CAR T cells. Finally, we identify potential interactions by which HRS cells inhibit T cells, among which the Galectin-1/CD69 and HLA-DRA/LAG3 interactions. However, high levels of inter-patient heterogeneity of the interaction strength were observed. In conclusion, this study identifies new potential therapeutic targets for cHL and highlights the importance of studying heterogeneity when identifying therapy targets.

  Dataset EGAD50000000626

• RNA-sequencing on thyroid samples from fetuses with Down syndrome and fetuses with no genetic/developmental abnormality

  The current data pertains RNA-sequencing reads obtained from thyroid samples acquired from fetuses with Down syndrome and fetuses with no genetic/developmental abnormality. Total RNA was isolated from left lobe from thyroid samples using a hand-held homogenizer and the Promega ReliaPrep RNA Miniprep System (Thermo Fisher Scientific). RNA yield was determined with the NanoDrop Microvolume Spectrophotometer (Thermo Fisher Scientific). Fragmentation and mRNA library preparation was performed using the Kapa mRNA Hyperprep Kit (Roche, Basel, Switzerland). Libraries were equimolar pooled and quality was checked on a TapeStation system using the DNA1000 ScreenTape (Agilent Technologies, Santa Clara, CA, USA). Libraries were sequenced with poly(A) selection to sequence all messenger RNA for gene expression analysis on the NovaSeq6000 PE150 (Illumina, San Diego, CA, USA), producing at least 40M 150-bp paired-end reads per library.

  Dataset EGAD50000000387

• WGS and WES of 78 pairs Chinese gastric cancer

  Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).

  Study EGAS00001001056

• Whole genome and RNA sequencing of paediatric glioblastoma in the ICGC PedBrain project

  Paediatric glioblastoma (pedGBM) is characterised by substantial intertumoural heterogeneity. In order to identify the genetic lesions underlying tumourigenesis, we analysed whole genomes and transcriptomes of pedGBMs and in vitro model systems by next generation sequencing. Novel fusions of the receptor tyrosine kinase MET lead us to investigate targeted therapy using MET inhibitors. This study is part of the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/).

  Study EGAS00001001139

• Genetic Landscape of Esophageal Squamous Cell Carcinoma Defined by Exome Sequencing on Chinese Patient Cohort and Cell Lines

  Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A.

  Study EGAS00001000932

• Much ado about nothing? - Off-target amplification can lead to false positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals

  Recent studies suggested the existence of (poly-)microbial infections in human brains. Using 16S rRNA gene amplicon sequencing, we tested the hypothesis that there is a bacterial brain microbiome. We evaluated brain samples from healthy human subjects and individuals suffering from PD (olfactory bulb and pre-frontal cortex). We identified off-target amplification as a major confounding factor in low-bacterial/high-host-DNA scenarios.

  Study EGAS00001004757

• Exome sequencing of DNA from pituitary neuroendocrine tumor (PitNET) and germline DNA from the same patient

  The goal of the project is to study tumor - normal DNA pairs from the PitNET patients. Total of 15 PitNET patients were recruited for the study to investigate sometic changes in the tumor compared to normal tissue. Illumina technology were used for sequencing and two data analysis pipelines employed for data analysis. Recurrent somatic variations were investigated and genomic disruption analysis from exome sequencing data attempted.

  Study EGAS00001004654

• RNA-Sequencing and Somatic Mutation Status of Adrenocortical Tumors: Novel Pathogenetic Insights

  To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and to identify new potential pathogenetic mechanisms, we performed transcriptome profiling by high-throughput sequencing. We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known genetic background: 26 adenomas with Cushing syndrome, 17 adenomas with mild autonomous cortisol secretion, 9 endocrine-inactive adenomas, 7 adrenocortical carcinomas. Additionally, we sequenced 4 control samples.

  Study EGAS00001004533

• Dual-mTOR inhibitor Rapalink-1 reduces prostate cancer patient-derived xenograft growth and alters tumor heterogeneity

  Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.

  Study EGAS00001004431

• WGBS data (CancerLocator study) of cell-free DNA derived from human blood

  The blood samples of eight lung cancer patients and one benign lung tumor patient are collected for this dataset. Blood samples were centrifuged first at 1,600 × g for 10 minutes, and then the plasma was transferred into new micro tubes and centrifuged at 16,000 × g for another 10 minutes. The plasma was collected and stored at -80⁰C. CfDNA was extracted from 5 ml plasma using the Qiagen QIAamp Circulating Nucleic Acids Kit and quantified by Qubit 3.0 Fluoromter (Thermo Fisher Scientific). Bisulfite conversion of cfDNA was performed by using EZ-DNA-Methylation-GOLD kit (Zymo Research). After that, Accel-NGS Methy-Seq DNA library kit (Swift Bioscience) was used to prepare the sequencing libraries. The DNA libraries were then sequenced with 150bp paired-end reads.

  Dataset EGAD00001003168

• SNV and indel calls from 8086 individuals in the British Autozygosity Populations BioResource dataset

  This includes variant calls (single nucleotide variants and small insertions/deletions) from 8086 (mostly British Pakistani/British Bangladeshi) individuals from the following studies: 1. 3781 British Pakistani/British Bangladeshi adults from East London Genes and Health 2. 2791 British South Asian mothers from Born in Bradford 3. 1428 British South Asian adults from Birmingham 4. 86 individuals (mixed ancestries) from families with rare diseases, from Queen Mary University London All of the Birmingham and most of the Born in Bradford samples were previously sequenced as part of PMID: 26940866. Mapping was done with bwa-mem and variant calling was carried out with GATK HaplotypeCaller. We removed variant sites for which the following was true: SNPs: "QD < 2.0 || FS > 30 || MQ < 40.0 || MQRankSum < -12.5 || ReadPosRankSum < -8.0" Indels: "QD < 2.0 || FS > 30 || ReadPosRankSum < -20.0"

  Dataset EGAD00001004581

• Intercellular nanotube-mediated mitochondrial transfer enhances T-cell metabolic fitness and antitumor efficacy

  We found that bone marrow-derived mesenchymal stromal cells (MSC) establish nanotubular connections with T cells in a Talin 2 (TLN2)-dependent manner and leveraged these intercellular highways to supply new mitochondria to CD8+ T cells. In this experiment we analyzed the transcriptional profile of T cells co-cultured with MSC containing MSC derived Mitochondria (MitoPositive), T cells co-cultured with MSC not containing MSC derived Mitochondria and control T cells.

  Study EGAS00001007356

• Relevance of TMPRSS2, CD163/CD206 and CD33 in clinical severity stratification of COVID-19

  Our main objective is to incorporate new markers to classify COVID-19 patients based on mild or severe disease progression. To achieve this, we characterize SNP genotypes in critical genes involved in SARS-CoV infection (ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants) and study the monocyte population by mass cytometry (CyTOF). Finally, the results obtained will be integrated to search for the best set of predictors of disease aggressiveness.

  Study EGAS00001007003

• Clinical impact of immune checkpoint inhibitor (ICI) response, DNA damage repair (DDR) gene mutations and immune-cell infiltration in subtypes of metastatic melanoma

  Our study identified that immune cell infiltration and DNA damage repair (DDR) gene mutations may have an impact in response to immune checkpoint inhibitors (ICI) treatment in metastatic melanoma but differs among melanoma subtypes. Therefore, a comprehensive understanding of the role of immune infiltration cells, DDR gene mutations and copy number alterations could act as prognostic biomarkers for the ICI treatment among metastatic melanoma subtype patients.

  Study EGAS00001005781

• Multiomic Sequencing of Paired Primary and Metastatic Small Bowel Carcinoids

  Small bowel carcinoids are insidious tumors that often have metastatic spread at the time of diagnosis. Limited studies on the mutational landscape of carcinoids indicate that the tumors have a relatively low mutational burden. Loss of chromosome 18q and loss of CDKN1B have been reported in a minority of tumors. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors.

  Study EGAS00001006988

• The Natural History of Human Prostate Cancer

  Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of 3 men. For each of three different prostates, multiple tumour samples (4, 5, and 3 depending on the case) and one normal tissue sample were whole genome sequenced with a matched blood sample using the Illumiuna HiSeq platform. Tumour samples were sequenced to a target depth of 50X and normals and blood to a target depth of 30X. As of September 2020, some of the studies using these data include: Cooper et al, Nature Genetics 2015 (PMID: 25730763) Wedge et al, Nature Genetics 2018 (PMID: 29662167) Pan-Cancer Analysis of Whole Genomes, Nature 2020 (PMID: 32025007)

  Dataset EGAD00001000689

• Genomic Evolution of Breast Cancer Metastasis and Relapse

  Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling.

  Dataset EGAD00001002696

• MultiOMICS study of a pair of infant monozygotic twins with concordant B-cell ALL (WGS)

  B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common cancer in childhood. Studying identical twins with B-cell ALL provides a unique and tractable model for deciphering the developmental timing of pre- and post-natal mutations contributing to clonal evolution. To date, this has mainly focused on major cytogenetic subgroups of childhood B-cell ALL, including MLL fusions, ETV6-RUNX1, hyperdiploidy, and BCR-ABL1. However, formal demonstration of the prenatal origin and “backtracking” the natural history of the leukemia remains understudied in “B-other”/Normal Karyotype (NK) B-cell ALL. To characterize the genetic landscape of this particular leukemia subtype, we performed whole genome DNA- and B-cell receptor (BCR)- on a pair of 8-month-old monozygotic twins diagnosed with concordant “B-other”/NK B-cell ALL.

  Dataset EGAD00001005017

• RNA-seq study of longitudinal blood cell samples drawn from children at risk of type 1 diabetes

  The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding auto-antibody positivity or reflect progressive b-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4, CD8 cell fractions and unfractionated PBMC samples longitudinally collected from seven children who developed beta-cell autoimmunity (case subjects) at a young age and matched control subjects.

  Dataset EGAD00001005767

• Profiling heterogeneity in Human derived IPSC-neurons (2020-05-18)

  The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer's and Parkinson's is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to use single-cell assays to study genetic effects during differentiation of dopaminergic and cortical neurons to identify the sequence of molecular events from variants to healthy and diseased cell states in a cell-specific manner. 1) 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/ . This dataset contains all the data available for this study on 2020-05-18.

  Dataset EGAD00001006157

• Induction of trained immunity by influenza vaccine: impact on COVID-19

  Cryopreserved PBMCs from 10 individuals before and after vaccination were used to perform single cell RNA sequencing. Equal number of cells per individual were pooled together (5 individuals per pool) and single-cell RNA sequencing was performed in paired-end mode on NovaSeq 6000 (Illumina) with a depth of 50,000 reads per cell. DNA was isolated from PBMCs and then used for genotyping by Illumina GSA Beadchip. This dataset contains the fastq sequence files, genotypes of the donors used for demultiplexing the pools and files indicating the linkages between individuals, pools and fastq files. The number of samples listed by EGA does not match the actual number of samples due to limitations on the upload scheme used.

  Dataset EGAD00001007827

• WGS of cell-free DNA derived from plasma of CRC patients and healthy controls, and WGS of matched tumor tissue and saliva

  This dataset contains: 1.) Whole-genome sequencing (WGS) data (~6x) of 259 cfDNA samples obtained from 50 colorectal cancer (CRC) patients and 61 healthy controls. Paired-end sequencing was performed with 2x101 bp reads on the NovaSeq 6000 system. Data is provided as mapped .bam files (aligned to GRCh38/hg38). 2.) WGS data (~1x) of 50 tumor biopsy and 45 saliva samples from CRC patients. Paired-end sequencing was performed with 2x101 bp reads on the NovaSeq 6000 system. Data is provided as mapped .bam files (aligned to GRCh38/hg38).

  Dataset EGAD00001009309

• Clonal origin of lineage switch leukemia following CAR-T cell and blinatumomab therapy

  Children with ALL treated with anti-CD19 therapy occasionally develop a phenotypically distinct AML. However, the precise clonal origin of such class switch leukemias remains unresolved. Here, we reconstructed the evolution of leukemia in a child with primary ALL, two ALL relapses and AML after treatment with anti-CD19 CAR-T and blinatumomab through whole-genome sequencing. The phylogeny revealed that the AML was a monoclonal outgrowth descending from the initial ALL and harbored biallelic loss of CDKN2A, PAX5 and TP53. However, none of the ALL or AML relapses directly descended from one another, suggesting the presence of a reservoir of persistent clones. Our findings suggest anti-CD19 treatment selects pre-existing clones, with many key genetic alterations underpinning the lineage switch detectable prior to treatment.

  Dataset EGAD00001009161

• Separation of chronic myeloid leukemia stem cells from normal hematopoietic stem cells at single-cell resolution

  We provide whole exome DNA sequening data in fastq format for 23 clinical samples of chronic myeloid leukemia stem cells (CML-SC) plus two buccal swipes derived normal samples. CML samples are comprised of 4 to 8 replicates from two patients, at diagnosis and after treatment. Single CML stem cells before treatment and single non-transformed hematopoietic stem cells (HSC) at remission were selected from bone marrow samples by FACS, according to newly identified genetic markers CD33+CD26+ at diagnosis and CD33+CD26-/CD33-CD26- at remission. WES libraries of colony forming assays derived CML-SC and HSC populations were prepared using Agilent SureSelect Human All Exon V6 kit and sequenced running 150 cycles (2x 75bp paired-end) on an Illumina NextSeq 500 platform.

  Dataset EGAD00001009847

• The G2 gene expression signature and MYC overexpression are independent poor prognostic factors in childhood high-grade osteosarcoma

  Key objective Are the prognostic transcriptomic G1/G2 gene expression signature, MYC overexpression, and MYC amplification replicable stratifying biomarkers for future clinical trials in high-grade osteosarcoma? Knowledge gathered In an unselected cohort, the G2 gene expression signature and MYC overexpression, but not MYC amplification, were independently associated with poor event-free and overall survival. Relevance Transcriptomic biomarkers may serve as stratifying factors that guide the management of patients with high-grade osteosarcoma. Current data underlines the importance of prospective validation of the G1/G2 signature and MYC overexpression in an international, multicenter, study.

  Dataset EGAD00001015503

• PCA Atlas Visium spatial transcriptomics data (FASTQs, spaceranger BAMs and Visium mapping tables)

  This dataset contains Visium spatial transcriptomics data for the PCA Atlas study EGAS00001008332. It includes: - Raw Visium FASTQ runs (EGAR00004172272–EGAR00004172283) for all libraries. - spaceranger alignment BAM analyses for those libraries where BAM output was generated. - visium.csv: a slide-level mapping table linking Visium slide samples to EGA sample accessions, sequencing runs/experiments and spaceranger BAM analyses. - visium_tma.csv: a TMA mapping table describing how mini-TMA slides relate slide-level Visium libraries to tissue-level samples/cores. Together these objects provide the raw and aligned Visium data and the technical/biological mappings needed to understand and reuse the spatial transcriptomics component of the PCA Atlas. High resolution histology images are available from the following Zenodo repository, along with additional spaceranger outs for each slide: - https://zenodo.org/records/17411292

  Dataset EGAD00001015796

• Variant calling dataset from the whole-exome study of CIRdb in the Canary Islands

  Sequence reads were obtained from a set of 920 unrelated individuals from the CIRdb using Illumina paired-end reads, at the Institute of Technology and Renewable Energy (ITER). Briefly, we used bcl2fastq v2.18 to perform sample demultiplexing and BWA-MEM v0.7.15 (https://github.com/lh3/bwa) to align reads to GRCh37/hg19 reference. Resulting BAM files were assessed with SAMtools v1.3 (http://www.htslib.org) and Picard v2.10.10 (https://broadinstitute.github.io/picard/) for quality control steps. Small insertions/deletions (< 50 bp) and single nucleotide variants (SNVs) were identified using an in-house bioinformatics pipeline based on GATK HaplotypeCaller v3.8 (https://gatk.broadinstitute.org/hc/en-us/articles/360037225632-HaplotypeCaller). This pipeline follows the Best Practices recommendations for germline variant calling and its description is publicly available (https://github.com/genomicsITER/benchmarking/tree/master/WES).

  Dataset EGAD50000002484

• University of Washington Developmental Single Cell Atlas

  We set out to generate a human cell atlas of both gene expression and chromatin accessibility using tissues obtained during development. In this study, we applied an assay for single cell profiling of gene expression based on three-level combinatorial indexing (sci-RNA-seq3) to 121 fetal tissue samples representing 15 organs, altogether profiling transcription in over 4 million single cells. In parallel, we devised an improved assay for single cell profiling of chromatin accessibility also based on three-level combinatorial indexing (sci-ATAC-seq3). We applied this method to 53 fetal tissue samples representing 15 organs, altogether profiling on the order of one million single cells. From these data, we identify and characterize diverse human cell types and annotate them with respect to marker genes, expression and regulatory modules. These data comprise a rich resource for the exploration of human biology.

  Study phs002003

• Genomic Analysis of Low Grade B-Cell Lymphoma

  We included tumors from 64 newly diagnosed or untreated Low Grade B-Cell Lymphoma (LGBCL) patients, consisting of SMZL (n = 48), NMZL (n = 6), EMZL (n = 2), LPL (n = 5), and B-NOS (n = 3) in this study. Samples were selected from cases consented to the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). RNA or DNA were extracted from 64 frozen LGBCLs tumors (with available matched germline DNA for N=61. For RNA sequencing, library preparation was done using the Illumina TruSeq RNA Exome Kit and sequenced with 100 nucleotide paired-end reads using the HiSeq 4000. For WES, library preparation was done using the Agilent SureSelect XT kit and sequenced with 100 nucleotide paired-end reads using the Illumina HiSeq 4000.

  Study phs002552

• Whole Genome Association Study of Bipolar Disorder

  The goal of the project is to identify genes that make individuals more susceptible to bipolar disorder (manic depressive illness) and to better understand the brain pathways involved in the disease. Dataset versioning Version 1: European-American (EA) ancestry only Version 2: Version 1 plus African-American (AA) ancestry Version 3: EA and AA samples plus updated diagnostic criteria Consent groups and participant set General research use (GRU): 1767 controls (1081 EA controls, 686 AA controls) This consent group includes all controls for the Bipolar study, which are a subset of controls for the Schizophrenia study (subset of Schizophrenia: GRU). Bipolar and related disorders (BARD): 841 cases (691 EA cases, 150 AA cases) This consent group includes a subset of the Bipolar cases. Bipolar disorder only (BDO): 653 cases (388 EA cases, 265 AA cases) This consent group includes a subset of the Bipolar cases.

  Study phs000017

• Breast Cancer Susceptibility

  Genetic factors account for a large fraction of breast cancer risk and it is estimated that up to 30% of breast cancers have a heritable component. Inherited cancer susceptibility is associated with early-onset of malignancies in general. Although 20% of young women with breast cancer have germline mutations in the best understood breast cancer susceptibility genes, BRCA1, BRCA2 and TP53, in the remaining 80% of women with early-onset breast cancer, the genetic factors contributing to disease remain unexplained. By studying the extreme phenotype of women diagnosed at an early age there is enrichment for genetic factors that contribute to breast cancer. This study contains the whole exome sequence of 384 women diagnosed with invasive breast cancer prior to 40 years of age. Each of the subjects reported a family history of breast cancer and lacked mutations in BRCA1 and BRCA2.

  Study phs001017

• Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

  This study describes a novel Immune Repertoire Sequencing technique, termed Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS), to reduce sequencing error while maintaining extremely high coverage and applies this technique to investigate the differential immune response to malaria between infants and toddlers. Despite a lower somatic hypermutation load, we found an unexpectedly high level of competency within the infant antibody repertoire, particularly the ability to diversify B cell clonal lineages upon acute infection. Detailed clonal lineage analysis encompassing lineages containing sequences from both pre- and acute malaria timepoints revealed an increase in somatic hypermutations upon acute infection. Further analysis on pre-malaria memory B cell containing lineages in toddlers who had previously been exposed to malaria provides evidence for the capacity of memory B cells to continue to mutate and isotype switch.

  Study phs001209

• Genome-Wide Analysis of Splenic Marginal Zone Lymphoma

  Splenic Marginal Zone Lymphoma (SMZL) is a B-cell malignancy of unknown pathogenesis and thus orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis of 8 paired tumor-normal DNAs from patients with SMZL, we show that the typical SMZL exome carries ~30 genetic alterations. Targeted resequencing of selected candidates in an extended panel of 40-117 samples revealed activating mutations of NOTCH2, a gene required for marginal-zone (MZ) development, as the most frequent and SMZL-specific lesion, accounting for approximately 20% of cases. Additional altered genes suggest that deregulation of signaling pathways normally involved in MZ development (NOTCH, NF-kappa B, and B-cell receptor) represents a critical event in SMZL pathogenesis. These findings have direct implications for the treatment of SMZL patients since drugs are available which can target NOTCH as well as other pathways deregulated in this disease.

  Study phs000502

• DAXX restoration suppresses alternative lengthening of telomeres in ATRX wild-type cells

  Many tumors maintain chromosome ends through a telomerase-independent, homologous recombination based mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes encoding components of the histone H3.3 chaperone complex, ATRX and DAXX. To date the mechanistic role of ATRX and particularly DAXX mutations in potentiating ALT remains poorly understood. We identify an osteosarcoma cell line, G292, with a unique chromosomal translocation resulting in loss of DAXX function, while retaining functional ATRX. Using this distinctive resource, we demonstrate that introduction of wild type DAXX suppresses the ALT phenotype and restores localization of the ATRX/DAXX complex to PML bodies. This provides the first direct molecular evidence that ongoing DAXX deficiency is essential for maintenance of the ALT phenotype and highlights the potential for therapeutic targeting of this oncogenic pathway.

  Study phs001495

• 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. The Massachusetts General Hospital (MGH) Atrial Fibrillation Study is utilized in the following dbGaP substudies. To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001001 Massachusetts General Hospital (MGH) Atrial Fibrillation Study. phs001116 MGH AF CHARGE-S phs001117 MGH AF Exome Sequencing phs001118 MGH AF Medical Resequencing

  Study phs001001

• Pancreatic Cancer Case Control Association Study

  Pancreatic cancer is the fourth leading cause of cancer death in the United States. This is in large part due to the rapidly fatal course of this disease, as the vast majority of patients die within months of diagnosis and the five-year survival rate is less than 5. We have brought together over 8000 participants from 9 studies of pancreatic cancer, to conduct a GWAS of pancreatic cancer. The studies were drawn from the Pancreatic Cancer Case-Control consortium and include case-control studies from the United States, Europe and Australia. Sites include: Johns Hopkins National Familial Pancreas Tumor Registry, Mayo Clinic Biospecimen Resource for Pancreas Research, Ontario Pancreas Cancer Study (OPCS), Yale University, MD Anderson Case Control Study, Queensland Pancreatic Cancer Study, University of California San Francisco Molecular Epidemiology of Pancreatic Cancer Study, International Agency of Cancer Research and Memorial Sloan Kettering Cancer Center.

  Study phs000648

• Host Response to Respiratory Infections

  In this study, we describe a strategy to identify undiagnosed respiratory viral infections through screening nasopharyngeal (NP) swabs for the chemokine CXCL10, which is highly induced in the nasopharynx as part of the host antiviral response. Using this strategy, we conducted two screens: first, we screened NP swabs collected at Yale New Haven Hospital (YNHH) in January 2017 from patients with undiagnosed respiratory viral infections and identified patients infected with seasonal coronaviruses and the relatively uncommon influenza C virus. Second, we screened samples from the beginning of March 2020 in the weeks before YNHH tested for SARS-CoV-2 and identified four patients that had undiagnosed SARS-CoV-2 infections. Sequences uploaded as part of this study include samples with rhinovirus, human coronavirus NL63, and 8 samples as part of the January 2017 screen for undiagnosed respiratory viral infections.

  Study phs002442

• Glioma International Case Control Study (GICC)

  The main goals of the GICC Study were: 1) to identify novel genetic risk variants for glioma, as well as validate variants implicated by previous genome-wide association studies of glioma; and 2) to explore biologically relevant gene-gene and gene-environment interactions in glioma susceptibility. The GICC Study includes participants from the following centers: Brigham and Women&#39;s Hospital (Boston, Massachusetts), Case Western Reserve University (Cleveland, Ohio), Columbia University (New York, New York), the Danish Cancer Society Research Centre (Copenhagen, Denmark), Duke University (Durham, North Carolina), the University of Texas MD Anderson Cancer Center (Houston, Texas), Memorial Sloan Kettering Cancer Center (New York, New York), the Mayo Clinic (Rochester, Minnesota), NorthShore HealthSystem (Chicago, Illinois), Umea University (Umea, Sweden), the University of California, San Francisco (San Francisco, California), the University of Southern California (Los Angeles, California), and the Institute of Cancer Research (London, United Kingdom).

  Study phs001319

• A Multimodal Atlas of Human Brain Cell Types

  "A multimodal atlas of human brain cell types" includes sample data targeting two cell types that show species differences between mouse and human. First, it includes a detailed transcriptomic, morphological, and electrophysiological characterization of cell types in layer 1 of human middle temporal gyrus, focusing primarily on different inhibitory cell types. This project also includes gene expression data collected from nuclei in layer 5 of human fronto-insula, with a goal of identifying transcriptomic signatures of Von Economo neurons. Control samples collected as part of the same experiment are also included in the data set. This study was conducted as part of a collaboration between the Allen Institute for Brain Science, the University of Szeged, and the J. Craig Venter Institute. Collaborators request that publications resulting from these data cite their original publication: Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (PMID: 30150662).

  Study phs001791

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Cleveland Clinic 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 collected by the Cleveland Clinic. 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, &#34;early age&#34; is defined as men 60 years of age or younger and women 70 years of age or younger.

  Study phs001871

• Validation of Gene Array to Predict Bacterial Co-infection In Adults Hospitalized with Viral Lower Respiratory Tract Infections (LRTI)

  Accurate tests for microbiologic diagnosis of lower respiratory tract infections (LRTI) are needed. Gene expression profiling of whole blood represents a powerful new approach for analysis of the host response during respiratory infection that can be used to supplement pathogen detection testing. Using qPCR, we prospectively validated the differential expression of 10 genes previously shown to discriminate bacterial and non-bacterial LRTI confirming the utility of this approach. In addition, a novel approach using RNAseq analysis identified 141 genes differentially expressed in LRTI subjects with bacterial infection. Using "pathway-informed" dimension reduction, we identified a novel 11 gene set (selected from lymphocyte, &#945;-linoleic acid metabolism, and IGF regulation pathways) and demonstrated a predictive accuracy for bacterial LRTI (nested CV-AUC=0.87). RNAseq represents a new and an unbiased tool to evaluate host gene expression for the diagnosis of LRTI.

  Study phs001248

• NIDDK International IBD Genetics Consortium Repository Global Screening Array

  The purpose of this GWAS meta-analysis is to assess IBD risk alleles using data collected by members of the International IBD Genetics Consortium and their collaborators around the world. Data from over 30 cohorts have been identified and are being combined for analysis. Genotyping has been conducted using a variety of chips with most samples genotyped using GSAMD-24v1-0 or GSA-CHO-Custom. Individual level genotype data will be made available whenever possible (some groups are only able to provide summary statistics due to institutional and/or governmental restrictions on data sharing), together with information on sex, self-reported ancestry, IBD affection status and diagnosis. This first batch includes data from North American sites who are members of the NIDDK-funded IBD Genetics Consortium. Additional data will be provided in an update as soon as they have gone through the QC process.

  Study phs002336

• Center for Common Disease Genomics (CCDG) - Cardiovascular: eMERGE - Northwestern 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 the NUgene Project biobank at Northwestern University. 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. In this study "early age" is defined as men 60 years of age or younger and women 70 years of age or younger.

  Study phs001913

• Infant Immune Responses to Early Life Vaccinations

  Infants are vulnerable to life-threatening infections due to an immature immune system. For this reason, vaccinations are provided early in life to increase protection against infectious agents. However, there is a limited understanding on how routine vaccinations alter the different immune cell populations in infants. Here, we profiled peripheral blood mononuclear cells (PBMCs) from six 2-month-old infants at the time of their routine vaccinations. Infants received the standard vaccinations including DTaP (diphtheria, tetanus and acellular pertussis), IPV (inactivated polio vaccine), Hep B (hepatitis B), Hib (Haemophilus influenzae type B), Rotavirus, and PCV13 (pneumococcus conjugate vaccine). Samples were obtained before vaccination, and subsequently around one week, and two-month post-vaccination (n=18 samples). This study sheds light on the dynamic nature of the infant peripheral immune cell transcriptome upon initial routine vaccine exposure. The processed data is available on GEO under GSE204716.

  Study phs002926

• NHLBI TOPMed - NHGRI CCDG: Malmo Preventive Project (MPP)

  The Malm&#246; Preventive Project (MPP) was a community-based disease prevention program including 33,346 inhabitants from the city of Malm&#246; in Southern Sweden. Complete birth cohorts between 1921-1949 were invited, and the participation rate was 71%. Participants underwent screening between 1974 to 1992 for cardiovascular risk factors, alcohol abuse, and breast cancer. Between 2002-2006, surviving participants were invited to a reexamination which included blood sampling from which DNA has been extracted. Subjects with prevalent or incident AF were identified from national registers as previously described, and cases with DNA were then matched in a 1:1 fashion to controls with DNA from the same cohort by sex, age (&#177;1 year), and date of baseline exam (&#177;1 year). Also, controls required a follow-up exceeding that of the corresponding AF case.

  Study phs001544

• Transfer Learning Associates CAFs with EMT and Inflammation in Tumor Cells in Human Tumors and Organoid Co-Culture in Pancreatic Ductal Adenocarcinoma

  This study examined the transcriptional changes induced by cancer associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma patient-derived tumor organoids. We hypothesized that cancer associated fibroblasts impacted tumor cell transcription to promote tumorigenic behavior. Using patient-matched cells from 3 patients, we compared the transcriptional profiles of patient-derived organoids in monoculture to patient-derived organoids co-cultured with CAFs. Similarly, we looked at the transcriptional changes in matched patient-derived cancer associated fibroblasts grown in monoculture or co-cultured with patient-derived organoids. With a focus on intercellular crosstalk, we identified crosstalk between cancer associated fibroblasts and patient-derived organoids through VEGFA and NRP1. This was identified by bulk RNA sequencing and examined dynamically in organoid-CAF co-culture. This dbGaP deposit is the bulk RNA sequencing data for these 3 patients.

  Study phs003563

• Genetic Analysis of Skin Cells

  Cutaneous squamous cell carcinoma (cSCC) is a form of skin cancer originating from keratinocytes in the skin. They have high mutation burdens, primarily driven by UV-radiation-induced DNA damage. The order in which mutations undergo selection during the evolution of cSCC is not known. A subset of cSCCs grow out of benign neoplasms called actinic keratoses. To better understand the evolution of cSCC, we identified cases of cSCCs adjacent to actinic keratoses. From these cases, we separately microdissected the surrounding normal skin, the actinic keratosis, and the cSCC, and we performed targeted DNA-sequencing on the tissue from each area. We reconstructed tumor phylogenies and performed spatial transcriptomics on the 10X FFPE Visium platform on a subset of cases. Collectively, these studies revealed the mutational and gene expression changes that arise during the evolution of cSCC.

  Study phs003282

• Long-Read Sequencing to Identify Inherited Mutations Predisposing to Breast Cancer

  We aimed to detect deeply intronic mutations within genes linked to breast/ovarian cancer that are potentially under-reported in clinical testing due to technical limitations. Current DNA and RNA tests typically exclude these regions, which harbor many variants within complex repetitive sequences that short-read sequencing cannot align. By employing targeted long read sequencing together with recent in silico prediction tools, we assessed the implications of rare deep intronic variants in severely affected patients with breast, ovarian, and/or metastatic prostate cancer, who had previously tested negative using standard genomic or cDNA methods. Through this approach, we identified participants who carried deep intronic mutations in tumor suppressor genes, resulting in abnormal transcripts causing premature truncations and loss of gene function. This study underscores the potential of long read DNA and cDNA sequencing in enhancing mutation discovery efforts.

  Study phs003638

• Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer: DNA Sequencing

  This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. All participants in this study were female. RNA sequencing data from the same patients were published under phs001863. Subject aliases are the same in the two datasets.

  Study phs003801