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• Longitudinal Study of Vaginal Flora

  This prospective observational study aims to advance our knowledge of the natural history and abnormal alteration in vaginal microbial flora, and to identify risk factors that are associated with these changes. A total of 5500 healthy, non-pregnant women of reproductive age will be enrolled and followed up in Birmingham, Alabama, for one year (baseline visit plus once every three months afterwards, totaling 5 visits). Detailed information on sociodemographic status, medical history, hygiene practice, sexual behavior and psychosocial stress will be collected through in-person interviews. Routine gynecological and dental examinations will be carried out during the study visits. Samples of vaginal secretion and blood will be collected. Laboratory tests to quantify vaginal microbial flora and to identify infection of bacterial vaginosis as well as common sexually transmitted diseases will be conducted. Future submissions may contain metadata or molecular data from additional subjects.

  Study phs002367

• Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: To determine the sensitivities and specificities of ventillation/perfusion (V/Q) lung scans for acute pulmonary embolism (PE).Participants: A total of 1487 participants were enrolled.Conclusions: Almost all participants with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism. Only in a minority of participants did the clinical assessment combined with the V/Q scan interpretation improve the overall chance of reaching a correct diagnosis of acute PE. Although a high probability scan usually indicated the presence of PE, only a small number of participants with PE had a high probability scan. Reference: PIOPED Investigators, 1990, PMID: 2332918.

  Study phs004020

• Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL

  In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.

  Study EGAS50000000582

• Immunogenomic analysis of tumor infiltrating B cells in gastric cancer

  Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. This study aimed at profiling the global picture of the humoral cancer immunity in view of immune repertoire characteristics of tumor-infiltrating B cells. In this study, we investigated B-cell repertoire (BCR) / immunoglobulin (Ig) sequencing of tumor infiltrating B cells in 102 clinical gastric cancers. First, total RNAs were extracted from frozen gastric cancer tissues and corresponding normal gastric mucosa; then, BCR/Ig repertoires of tumor-infiltrating B cells were amplified by target PCR using multiplex primer sets available from iRepertoire(R), inc. Subsequent next-generation sequencing data obtained by the Illumina platform were aligned onto human BCR/Ig repertoire sequence. This dataset contains the repertoire sequencing data of 102 gastric cancer cases analyzed in this study.

  Study JGAS000242

• The function of circular RMST in neuroendocrine tumours

  Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC using total RNA-seq profiling of patient samples. In addition, circRMST is also abundantly expressed in SCLC. Functional studies using shRNA, siRNA, CRISPR-Cas13 and Cas9 consistently demonstrate that circRMST is essential for tumour growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription.

  Study EGAS50000000897

• Analysis of the co-occurrence of LOY and CHIP in Alzheimer's disease patients and control individuals using whole-exome sequencing (WES)

  We performed deep whole-exome sequencing of FACS-isolated CD4+ T lymphocytes, NK and myeloid cells from men with AD and controls exhibiting either LOY or retention of Y chromosome (ROY). We found 39 sequence variants in known (canonical) myeloid driver genes of clonal hematopoiesis (MD-CH) and known lymphoid driver genes (LD-CH), and maximally 14 (35%) of these could co-exist with LOY within the same clone. We further describe 192 unknown drivers of clonal hematopoiesis (UD-CH), which were markedly enriched in AD-LOY individuals (odds ratio=4.8, Benjamini-Hochberg-adjusted p=0.041), and over 20% of these variants were protein-truncating. In myeloid cells, the total burden of all detected drivers correlated with the percentage of LOY cells (Spearman ρ=0.52, adjusted p=0.00041).

  Study EGAS00001008234

• Functional_genomics_approaches_to_understand_osteoarthritis

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics). We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression. 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 EGAS00001002322

• Genome-wide DNA methylation profiles by MeDIP-seq of cord blood cells and cord blood mononuclear cells obtained from twins conceived through in vitro fertilization and naturally conceived controls

  The study included 47 newborn twins conceived though in vitro fertilisation (IVF) and 60 non-IVF-conceived twins from the Peri/postnatal Epigenetic Twins Study (PETS). Cord blood was collected at birth and used to process mononuclear cells. Whole blood cells (WBCs) from cord blood of 98 twins (40 IVF and 58 non-IVF) and cord blood mononuclear cells (CBMCs) of 82 twins (35 IVF and 47 non-IVF) were subjected to DNA methylation profiling. Methylated DNA immunoprecipitation followed by deep sequencing (MeDIP-seq) was applied to generate genome-wide DNA methylation profiles in a total of 180 samples. Single-end reads were mapped onto hg19 using BWA. Methylation levels were quantified using MEDIPS and used to identify IVF-associated differentially methylated regions.

  Study EGAS00001002248

• Functional_genomics_approaches_to_understand_osteoarthritis

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics). We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression. 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 EGAS00001002255

• Genomic Heterogeneity and the Small Renal Mass

  Tumor heterogeneity is believed to represent a barrier to pre-operative genomic characterization in kidney cancer. Previous studies of heterogeneity in clear cell renal cell carcinoma (ccRCC) evaluated only large and metastatic tumors. In small renal tumors in which multiple biopsies are not feasible, the extent of heterogeneity remains unknown. In this study, we evaluated how the extent of genomic heterogeneity in small and large ccRCC. A total of 23 small (<4cm ) and 24 large (>7cm ) ccRCC had 3 regions sampled for evaluation of copy number, clear-cell A/clear-cell B (ccA/ccB) classification, and cell cycle progression (CCP) score. Small tumors have less genomic complexity and significantly fewer subclonal events. Pre-treatment genomic characterization based on a single biopsy in small ccRCC can provide insight into biologic potential to make clinical decisions.

  Study EGAS00001002919