12322 results for ""statistically+reactive"+taxa+in+microbial+community"

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• Genomic Characteristics of Myeloproliferative Neoplasms in Patients Exposed to Ionizing Radiation following the Chernobyl Nuclear Accident

  The study "Genomic Characteristics of Myeloproliferative Neoplasms in Patients Exposed to Ionizing Radiation following the Chernobyl Nuclear Accident" was designed as case-control study. We studied genomic characteristics of chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPNs) in Ukrainian patients who were previously exposed to Ionizing Radiation (IR) due to Chernobyl accident in comparison to unexposed MPN patients and controls (previously exposed to IR due to Chernobyl accident and unexposed people who were not diagnosed with any oncological condition at the moment of DNA sampling).

  Study phs001761

• In Vivo Cytokine eQTL Interactions from a Lupus Clinical Trial

  The purpose of this study is to discover in vivo cytokine expression quantitative trait locus (eQTL) interactions from a cohort of patients with systemic lupus erythematosus. 157 lupus patients were enrolled in a clinical trial to test the efficacy and safety of an anti-IL-6 monoclonal antibody. At three time points, we measured interferon (IFN) status, anti-IL-6 drug exposure and genome-wide gen expression. We identified 4,818 cis-eQTLs and then observed a statistically significant enrichment of in vivo eQTL interactions with IFN status and anti-IL-6 exposure.

  Study phs001702

• Patient Microbiome and Surgical Site Infection in Spine Surgery

  Single center, prospective cohort study on the contribution of the preoperative patient microbiome and resistome to surgical site infection (SSI) and resistance to surgical antibiotic prophylaxis in spine surgery. The samples in this entry comprise a subset of patients for whom paired preoperative microbiome samples and postoperative wound culture isolates were obtained. These samples were analyzed by Illumina-based sequencing of metagenomic libraries enriched for the SSI pathogen of interest using the GenCap-Seq methodology (PMID: 36121157) to identify instances of endogenous infection with strains present in the preoperative microbiome.

  Study phs003358

• Spermidine/spermine N1-acetyltransferase controls tissue-specific regulatory T cell function in chronic inflammation

  In this project we wanted to understand the role of tissue resident regulatory T cells with the aim of finding commonalities between multiple inflammatory diseases namely psoriasis, sarcoidosis and inflammatory bowel disease. Using single cell sequencing data we found that specifically in the skin, Spermidine/spermin N1-acetyltransferase seems to mediate a „fragile“ Treg phenotype. To test the influence of the tissue on this phenotype we also sought to charactierize a similar population in patient PBMCs for which we generated this data.

  Study EGAS50000000745

• High Resolution Analysis of Spatial Interactions of Hundreds of Promoters in HeLa Cells

  In this study we developed a new hybridisation-based promoter Capture-C protocol that makes use of biotinylated dsDNA probes and allows high-resolution promoter interactome description. Experiments aimed to describe spatial interactions of set of 861 promoters were performed in HeLa cells. We have found that enrichment efficiency and quality of final libraries in our study is on a par with established promoter Capture-C protocols. Meanwhile, our version of the probe preparation protocol is reasonably simple and makes Capture-C experiments more affordable and flexible.

  Study phs002014

• Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing

  Taxanes are key drugs in the treatment of breast cancer, but some breast cancers are resistant to taxanes. Obtaining extensive genomic information in a short time has recently become possible. We used whole exome-sequencing (WES) to investigate mechanisms of taxane resistance in human breast cancer. We selected six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy. We then performed WES of these samples and identified somatic mutations of candidate genes that are thought to affect taxane resistance.

  Study JGAS000370

• ctDNA Quantification in Blood Plasma Using Deep Learning Based Fragle Tool

  The project aims to develop an easy to use software named Fragle that can quantify ctDNA in blood plasma. This can help in cancer screening and progress monitoring from simple blood test without any need for tumor biopsy. We aim to make Fragle usable for both low pass whole genome sequencing and targeted sequencing data of cell free DNA. Fragle can work directly on the raw bam files mapped to hg19/GRCh37. We are uploading the bam files used in this study for Fragle evaluation.

  Study EGAS50000000122

• A New CA19-9 Cut-Off Value Identifies Lewis Antigen Status and Refines Prognostic Stratification in PDAC

  This study investigates the clinical utility of serum CA19-9 levels in pancreatic ductal adenocarcinoma (PDAC), with a focus on identifying patients with Lewis antigen–negative status due to germline FUT3 variants. Using data from multicenter prospective cohorts in Taiwan, we analyzed CA19-9 classification, FUT2/FUT3 genotypes, and clinicopathological annotations. The goal of this study is to refine prognostic stratification and reduce false-negative interpretation of CA19-9 in PDAC patients. All participants provided informed consent, and the study was approved by the relevant institutional review boards.

  Study EGAS50000001575

• We screened 2.5 million SNPs in 161 individuals from 13 Sahelian populations from Western, Central and Eastern parts of the belt, and including both nomadic and sedentary groups

  We confirmed the role of the Sahel belt as a main corridor for human migrations across the African continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection.

  Study EGAS00001001610

• Pediatric tumor in a single child of three large nuclear families

  We identify three nuclear families in which a pediatric tumor had been diagnosed in a single child and neither parent had been diagnosed with cancer. These families had 4, 5, and 7 children, respectively. Diagnoses included Wilms tumor, low-grade astrocytoma, and Burkitt’s lymphoma, respectively. We used whole-genome sequencing to profile normal cells from each family member and a linked-read technology for genomic phasing, which enabled us to identify compound-heterozygous and de novo variants in addition to simple-heterozygous and homozygous-alternate variants.

  Study EGAS00001005321

• CUT&RUN of AML1-ETO binding occupancy following miR-130a KD in Kasumi-1 cells

  We performed CUT&RUN assay with control Ig , anti-Flag and anti-ETO antibodies in Flag-tag AML1-ETO Kasumi-1 cells to determine binding occupancy of AML1-ETO following miR-130a KD. Kasumi-1 cells were transduced in 3 independent replicates for control and miR-130a KD samples with lentiviruses containing GFP reporter gene. GFP+ cells were sorted 3 days post-transduction and the cells were used in the CUT&RUN assay. Three antibodies were used for each biological sample.

  Study EGAS00001005867

• Gene signature for predicting homologous recombination deficiency in triple-negative breast cancer

  We developed a gene expression-based classifier for homologous recombination deficiency (HRD) in breast cancer patients using WES and RNA-seq data obtained from 94 TNBC samples from a Malaysian hospital-based cohort (MyBrCa). This classifier was able to predict for high levels of a mutational signature associated with HRD in an additional MyBrCa TNBC validation cohort (this EGA study) as well as in TNBCs from TCGA. We also validated the classifier on a NanoString platform with both fresh frozen and FFPE tissue.

  Study EGAS00001006518

• Somatic mutation in edited cholangiocyte organoids

  Primary human cells cultured in organoid format have great promise as potential regenerative cellular therapies. However, their immunogenicity and mutagenic profile remain unresolved, impeding effective long-term translation to the clinic. In this study we report, for the first time, the generation of human leukocyte antigen (HLA)-I and HLA-II knock-out human expandable primary cholangiocyte organoids (PCOs) using CRISPR-Cas9 as a potential ‘universal’ low-immunogenic therapy for bile duct disorders. HLA-edited PCOs (ePCOs) displayed the same phenotypic and functional characteristics as parental unedited PCOs. Despite minimal off-target edits, duplex sequencing approaches demonstrated that ePCOs and PCOs acquire mutations in culture at similar rates, but without evident selection for cancer-driver mutations. ePCOs induced reduced T cell-mediated immunity and donor-dependent NK cell cytotoxicity in vitro and evaded cytotoxic responses with increased graft survival in humanized mice in vivo. Our findings have important implications for assessment of safety and immunogenicity of primary cell-derived organoid cellular therapies.

  Dataset EGAD00001015455

• Transcriptional consequences of SETBP1 variants in developmental disorders and malignancies

  The SETBP1 gene encodes a DNA-binding nuclear protein that regulates gene expression across multiple tissues. Precise control of SETBP1 dosage is essential for normal cellular function, as both loss- and gain-of-function variants of SETBP1 can lead to severe phenotypic consequences. De novo germline gain-of-function point mutations that prolong SETBP1 half-life result in Schinzel-Giedion syndrome (SGS), an ultra-rare and severe congenital disorder associated with extensive developmental abnormalities and health complications. These SGS-associated variants cluster within a hotspot in the SKI-homology domain of SETBP1, overlapping with somatic mutations recurrently observed in myeloid leukaemia with poor prognosis. Thus far, the precise mechanisms by which these SETBP1 mutations drive disease remain largely unclear. Here, through single-cell and single-nucleus mRNA sequencing of a rare collection of primary patient samples with SGS and myeloid leukaemia, we examined the transcriptional consequences of SETBP1 gain-of-function variants in haematopoietic cells, comparing their impacts when acquired in the germline and somatically in malignancies.

  Dataset EGAD00001015482

• Exome-seq data of two non-obstructive azoospermia patients

  Azoospermia, characterized by the absence of spermatozoa in the ejaculate is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in SPINK2, encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings we observed that homozygous Spink2 KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest. We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit towards the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.

  Dataset EGAD00001003326

• The landscape of somatic mutation in normal colorectal epithelial cells

  The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic events and consequent clonal expansions leading to cancer. As for most cancer types, however, understanding of the earliest phases of colorectal neoplastic change, which may occur in morphologically normal tissue, is comparatively limited because of the difficulty of detecting somatic mutations in normal cells. Each colorectal crypt is a small clone of cells derived from a single recently-existing stem cell. Here, we sequenced hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed, some ubiquitous and continuous, others only found in some individuals, in some crypts or during some phases of the cell lineage from zygote to adult cell. Likely driver mutations were present in ~1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium.

  Dataset EGAD00001004192

• Somatic mutations and clonal dynamics in healthy and cirrhotic human liver

  Chronic liver injury predisposes to cirrhosis and hepatocellular carcinoma, but how somatic mutations accumulate in liver disease is unexplored. We sequenced whole genomes of 400 microdissections of 100-500 hepatocytes from 5 normal and 6 cirrhotic livers. Compared to normal liver, cirrhotic liver had higher mutation burden, especially structural variants, including chromothripsis. Cirrhotic nodules were oligoclonal; sometimes entirely derived from a single, recent common ancestor. Clonal expansions millimeters in diameter occurred in cirrhosis in the absence of known driver mutations. Endogenous mutational processes predominated, although signatures of polycyclic aromatic hydrocarbon and aristolochic acid exposure occurred in some samples. Up to 10-fold within-patient variation in activity of exogenous signatures existed between adjacent cirrhotic nodules, with both clone-specific and microenvironmental forces shaping this heterogeneity. Synchronous hepatocellular carcinomas drew from the same repertoire of mutational signatures as background cirrhotic liver, but with higher burden. Somatic mutations chronicle the exposures, toxicity, regeneration and clonal structure of liver tissue as it progresses from health to disease.

  Dataset EGAD00001004578

• Somatic mutation in edited cholangiocyte organoids

  Primary human cells cultured in organoid format have great promise as potential regenerative cellular therapies. However, their immunogenicity and mutagenic profile remain unresolved, impeding effective long-term translation to the clinic. In this study we report, for the first time, the generation of human leukocyte antigen (HLA)-I and HLA-II knock-out human expandable primary cholangiocyte organoids (PCOs) using CRISPR-Cas9 as a potential ‘universal’ low-immunogenic therapy for bile duct disorders. HLA-edited PCOs (ePCOs) displayed the same phenotypic and functional characteristics as parental unedited PCOs. Despite minimal off-target edits, duplex sequencing approaches demonstrated that ePCOs and PCOs acquire mutations in culture at similar rates, but without evident selection for cancer-driver mutations. ePCOs induced reduced T cell-mediated immunity and donor-dependent NK cell cytotoxicity in vitro and evaded cytotoxic responses with increased graft survival in humanized mice in vivo. Our findings have important implications for assessment of safety and immunogenicity of primary cell-derived organoid cellular therapies.

  Dataset EGAD00001015457

• Somatic mutation in edited cholangiocyte organoids

  Primary human cells cultured in organoid format have great promise as potential regenerative cellular therapies. However, their immunogenicity and mutagenic profile remain unresolved, impeding effective long-term translation to the clinic. In this study we report, for the first time, the generation of human leukocyte antigen (HLA)-I and HLA-II knock-out human expandable primary cholangiocyte organoids (PCOs) using CRISPR-Cas9 as a potential ‘universal’ low-immunogenic therapy for bile duct disorders. HLA-edited PCOs (ePCOs) displayed the same phenotypic and functional characteristics as parental unedited PCOs. Despite minimal off-target edits, duplex sequencing approaches demonstrated that ePCOs and PCOs acquire mutations in culture at similar rates, but without evident selection for cancer-driver mutations. ePCOs induced reduced T cell-mediated immunity and donor-dependent NK cell cytotoxicity in vitro and evaded cytotoxic responses with increased graft survival in humanized mice in vivo. Our findings have important implications for assessment of safety and immunogenicity of primary cell-derived organoid cellular therapies.

  Dataset EGAD00001015456

• Analyzing the expression profiles of genes in ureters with and without indwelling stents using RNAseq 

  The objective of the work is to explore the pathways and mechanisms driving inflammation and fibrosis in stented ureters. In total, 6 pigs underwent cystoscopic unilateral ureteral stent insertion for 14 days. Ureteral tissue was harvested in 3 pigs, while the remaining 3 pigs had their stents removed, and were recovered for 7 days. Three separate pigs served as controls. Stents cause significant inflammation and fibrosis of ureters. Gene set enrichment analysis confirmed fibrotic changes and tissue proliferation and suggests that epithelial-mesenchymal transition is a driver of fibrosis.

  Study EGAS00001006855

• Systemic Lupus Erythematosus Serum Stimulation of Human Intestinal Organoids Induces Changes in Goblet Cell Differentiation and Mitochondrial Fitness

  SLE serum stimulation induced a unique expression profile in human colon organoids marked by a reduction in goblet cell marker expression and mucus composition. Transcriptomic analysis of SLE human colon biopsies displayed a downregulation of epithelial secretory markers. Collection of raw sequencing data used in this publication https://doi.org/10.1101/2023.07.04.547690

  Dataset EGAD50000000018

• Paired primary and recurrent patient GBM sample EZH2 binding profiles

  To ascertain the change in PRC2 occupancy at different promoter sets between primary and recurrent tumour, we performed EZH2 ChIPseq in longitudinal GBM samples from one Up and one Down responder from our cohort.

  Study EGAS50000000100

• NeuroCHARGE Consortium GWAS of White Matter Hyperintensities on MRI

  Meta-analysis results of white matter hyperintensities (WMH) volume genome wide association study (GWAS) in older population-based studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium and the UK biobank.

  Study phs002227

• Study of Lyme Immunology and Clinical Events (SLICE)

  The overall objective of this study is to measure risk factors, symptom patterns and severity, longitudinal course, and associated biomarkers in patients who develop symptoms of post treatment Lyme disease (PTLD) in cohort studies.  

  Study phs002793

• Human Autism Genetics

  The goal of this study is to bring together the power of 1) whole exome sequencing, 2) homozygosity mapping in consanguineous families, and 3) transcriptional analysis in brain tissue to identify genetic causes of autism spectrum disorders (ASD).

  Study phs000639