1248 results for ""halted+early"+"slower-than-anticipated+enrollment"+hospitalized+oral+adaptive+platform"

in 6.24 milliseconds.

• 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

• Single-cell roadmap of immune cell responses in chronic myeloid leukemia

  To study the innate and adaptive immune responses in CML, we profiled 25 samples from CML patients including samples at diagnosis (n = 7, N = 9, where n is the number of subjects and N the number of samples if different from n) and before and after TKI-cessation with imatinib (n = 6, N = 15) with paired single-cell RNA and T cell receptor (TCR) αβ chain sequencing (scRNA+TCRαβ-seq) and compared our data to different cancers (n = 29) and healthy donors (n = 7). This dataset contains the samples from before and after TKI-cessation, please see the manuscript for info related to the other datasets.

  Study EGAS00001005044

• BLUEPRINT EpiVar ChIP-seq in lineage specifying transcription factors

  The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise "experimental noise" and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.

  Dataset EGAD00001004571

• Picuris Pueblo oral history and genomics reveal continuity in US Southwest

  Following the decision of Picuris Pueblo to study their population history using DNA, this project generated 16 ancient and 13 present-day genomes from the Pueblo, spanning 1,000 years of history.

  Study EGAS50000000855

• Whole Exome sequencing of Gingivo-buccal Cancer - ICGC India Project Batch04

  This dataset pertains to whole exome sequencing of paired DNA samples of Gingivo-buccal oral cancer patient.DNA was isolated from the tumor and blood tissues of 47 patients (94 samples).We have performed Nextera exome capture and sequenced exome libraries in Illumina HiSeq platform.We have uploaded BWA-ALN aligned BAM files.

  Dataset EGAD00001003987

• MCRI-WEHI GRREAT Ataxia Sequencing Cohort

  This study evaluated the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Long-read adaptive sequencing (LR-AS) was performed to identify pathogenic RE in 67 genes.

  Dataset EGAD50000000815

• Bulk RNASeq of metastatic colorectal cancer organoids treated with crenigacestat alone or in combination with cetuximab

  Bulk RNA sequencing was performed on mCRC organoids cultured under untreated conditions or treated with crenigacestat alone or in combination with cetuximab. This dataset was generated to investigate the transcriptional changes associated with combination therapy and to compare these profiles with the adaptive responses observed following cetuximab monotherapy in the corresponding ATOH1 wild-type and knockout organoid models.

  Dataset EGAD50000002061

• Enrichment of Lung Microbiome with Supraglottic Taxa which is Associated with Increased Pulmonary Inflammation

  Background: The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that micro-aspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. Methods: We sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (9 never-smokers, 14 former-smokers and 6 current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes and neutrophils. Results: BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT. Smoking had no effect on pneumotype allocation, alpha or beta diversity. PneumotypeSCT was associated with higher BAL lymphocyte-count (p = 0.007), BAL neutrophil-count (p = 0.034) and eNO (p = 0.022). Conclusion: A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation.

  Study phs000633

• scRNAseq for patients with immunodeficiency and HCs

  The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.

  Study EGAS00001007271

• Genomic evolution of pancreatic cancer at single-cell resolution

  This project assesses genomic evolution of pancreatic cancer using the Mission Bio Tapestri platform and Whole Exome Sequencing. The Mission Bio Tapestri platform is a single-cell DNA sequencing platform using a targeted gene panel to assess SNV/CNV. Several samples, including primary and metastatic tissue, were used to investigate changes at single-cell resolution.

  Study EGAS50000001351