659 results for ""option,com_discussions"+y+19"

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• P647_Targeted_resequencing_project

  In collaboration with Dr Robert Semple we have identified a family harbouring an autosomal dominant variant, which leads to severe insulin resistance (SIR), short stature and facial dysmorphism. This family is unique within the SIR cohort in having normal lipid profiles, preserved adiponectin and normal INSR expression and phosphorylation. DNA is available for 7 affected and 7 unaffected family members across 3 generations. All 14 samples have been genotyped using microsatellites and the Affymetrix 6.0 SNP chip. Linkage analysis identified an 18.8Mb haplotype on chromosome 19 as a possible location of the causative variant. However, Exome sequencing of 3 affected and 1 unaffected family members has not identified the causative variant suggesting the possibility of an intronic or intergenic variant in this region or elsewhere in the genome. We propose to conduct whole genome sequencing of 5 members of the pedigree at a depth of 20X. The chosen samples are two sets of parents plus one member of an unaffected branch of the pedigree who shares the risk haplotype on chromosome 19. Sequencing of the two sets of parents will be used along with the genome-wide SNP data to impute 4 affected children giving an effect sample size of 6 affected individuals.

  Study EGAS00001000305

• Botswana 15 autosomal unlinked microsatellites

  Population structure was investigated in 990 Botswana individuals according to ethno-linguistics, Bantu and Khoisan, and geography (the nine administrative districts) using the AmpFLSTR Identifiler autosomal microsatellite markers. Genetic diversity and forensic parameters were calculated for the overall population, and according to ethno-linguistics and geography. The overall combined power of exclusion (CPE) was 0.9999965412 and the combined match probability 6,28 x 10-19. CPE was highest for the Khoisan Tuu ethnolinguistic group and the Northeast District at 0.9999582029 and 0.9999922652 respectively. CMP ranged from 6.28 x 10-19 (Khoisan Tuu) to 1,02 x 10-18 (Northwest district). Using pairwise genetic distances (FST), analysis of molecular variance (AMOVA), factorial correspondence analysis (FCA), and the unsupervised Bayesian clustering method found in STRUCTURE and landscape genetics software TESS, ethno-linguistics were found to have a greater influence on population structure than geography. FCA showed clustering between Bantu and Khoisan, and within the Bantu. This Bantu sub-structuring was not seen with STRUCTURE and TESS, which detected clustering only between Bantu and Khoisan. The patterns of population structure revealed highlight the need for regional reference databases that include ethno-linguistic and geographic location information. These markers have important potential for bio-anthropological studies as well as for forensic applications.

  Study EGAS00001002380

• Genomic Landscape of Cutaneous Diffuse Large B Cell Lymphoma

  Cutaneous diffuse large B cell lymphomas (DLBCL) are aggressive lymphomas with a poor prognosis. To elucidate their genetic bases, we performed whole exome capture and massively parallel sequencing on 19 tumor samples of diffuse large B cell lymphoma, leg type (DLBCL-LT) and 6 samples of secondary cutaneous diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS). Tumor specimens and their associated sequencing data were from multiple institutions, including Northwestern University (Chicago, IL), Massachusetts General Hospital (Boston, MA), and Medical University of Graz (Graz, Austria).

  Study phs001645

• Detecting PKD1 variants in Polycystic Kidney Disease patients by single-molecule long-read sequencing

  A genetic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is challenging. However, long-read single-molecule sequencing has been shown to be a reliable alternative strategy that could overcome PKD1 complexities. Using long-read sequencing to characterize a cohort of 19 patients with ADPKD, we developed an approach that provided high sensitivity in identifying PKD1 pathogenic variants, with a diagnostic yield of 94.7%. Reliable screening of ADPKD patients in a single test without interference of PKD1 homologous sequences is now possible.

  Study EGAS00001002106

• KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population

  The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 818 Finnish biobank samples genotyped for 5774 KIR-region SNPs and analysed for KIR gene content with targeted sequencing.

  Study EGAS00001005457

• Oesophageal adenocarcinoma RNAseq from LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19)

  This dataset contains bulk transcriptomes from the inoperable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19). Transcriptomes were prepared from pre-treatment oesophageal tumour biopsies using a ribodepletion approach in order to assess both previously reported (e.g. PD-L1 expression) and novel predictive expression-based biomarkers for immunochemotherapy treatment in this setting. On-treatment and post-treatment biopsies were generated as well to characterize response to therapy, and samples were also prepared from paired normal GI tissues for a subset of patients. scRNA-seq based deconvolution was also applied to bulk transcriptomes in this study to estimate the cell composition of tumour biopsies and assess the link between the presence of specific cell types with immunochemotherapy outcomes.

  Dataset EGAD00001009399

• Small molecule inhibitors of LOXL synergize with 5-AZA to restore erythropoiesis in myeloid neoplasms

  Objectives: Bone marrow (BM) stroma and microenvironmental factors in the BM milieu of myeloid neoplasms are increasingly being recognized as novel perspective therapeutic targets. Lysyl oxidases (LOX/LOXL) are crucial enzymes that cross-link collagen and contribute to the deposition of aberrant stiff extracellular matrix (ECM) in the BM of patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). Here, we studied whether inhibition of LOX/LOXL enzymes produced by BM-derived MSCs favors the differentiation of MDS/MPN hematopoietic stem cell and progenitor cells (HPSCs) and enhances the effects of 5-azacytidine (5-AZA). Methods: Primary co-cultures of MSCs and HPSCs were established from n=31 MDS/MPN patients and treated with the pan-LOX/LOXL inhibitor PXS-5505, 5-AZA or the combination of both for 4 days. At the end of co-culture, HSPC differentiation was assessed by CFU assays and flow cytometry. In some of the experiments, MSCs monolayers were pre-treated or not with PXS-5505 for 6 days and decellularized using 20 mM ammonia. Subsequently, autologous HSPCs were cultured on ECM matrices in the presence of 5-AZA or PXS-5505 + 5-AZA combination with or without inhibitors of integrin signaling such as blebbistatin, Y-27632 and αvβ3-integrin blocking antibodies. Patient-derived xenografts (PDX) were established in NSG mice based on intrafemoral co-injection of HSPCs and autologous MSCs. PDX were treated with 3 cycles of 5-AZA (75 mg/m2), PXS-5505 (30 mg/kg on alternate days for the duration of 5-AZA treatment) or combination of both. Results: MSCs of MDS and MPN patients displayed significant overexpression of LOX/LOXL transcripts as compared to healthy age-matched controls. Remarkably, LOX/LOXL inhibition in MSCs/HSPCs co-cultures increased erythroid differentiation of patient HSPCs that had suboptimal or no response to 5-AZA alone. From a total of n=31 advanced stage MDS/MPN patients, n=11 (35.5%) responded to the combination treatment, which was evidenced by a significant increase of CD235a+CD45- erythroid cell production compared to 5-AZA/PXS/untreated arms (p<0.05). Of note, combination treatment with 5-AZA + PXS-5505 facilitated differentiation of CD235+ erythroid progenitors from HSPCs sub-clones with low mutational VAFs. The presence of MSCs was necessary for the effects of the combination treatment and required direct cell contacts between MSCs and HSPCs. Moreover, PXS-5505-mediated alterations of the ECM composition alone were sufficient to induce erythroid differentiation. Inhibition of integrin-mediated signaling using blebbistatin, Y-27632 and αvβ3-integrin antibodies completely abrogated the effects of PXS-5505 induced erythroid differentiation. In vivo, the combination of PXS-5505 + 5-AZA favored erythroid differentiation of HSPCs and confirmed the in-vitro results. The combination treatment of 5-AZA + PXS-5505 induced the greatest reduction of disease burden as assessed by decrease of spleen indexes, total engraftment rates, BM fibrosis and mutational VAF profiles. Conclusions: The combination of 5-AZA + LOX/LOXL inhibitor PXS-5505 in MDS and MPN synergistically restores erythropoietic differentiation of primary HSPCs. The effect is dependent of contact interaction between HSPCs and niche components, such as MSCs and MSCs-derived ECM. Our data propose a strong rationale for a BM niche targeted combination treatment with 5-AZA + PXS-5505 in transfusion dependent MDS and MPN, which will be assessed in forthcoming clinical trials.

  Study EGAS00001006174

• Total RNAseq in the sporadic ALS and healthy control motor cortex

  The motor cortex is the earliest affected brain region in ALS. This dataset contains total RNA sequencing (stranded, 2x101bp) data derived from the motor cortex of 11 sporadic ALS patients and 8 healthy controls.

  Dataset EGAD00001006022

• Cohort of NGS lymphoma samples used as control

  Control cohort of lymphoma samples sequenced with a hybrid capture panel designed to be able to detect translocations and mutations in lymphoma samples. used in the paper "Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing"

  Dataset EGAD00001007711

• Pacbio HiFI Whole-Genome Sequecing of Trios with Intellectual Disability

  6 trios and 1 proband were whole genome sequenced with PacBio Sequel II to a depth of 30X, using the HiFi chemistry. For each trio the proband was affected with severe ID, and the parents were unaffected. Samples are grouped by trio.

  Dataset EGAD00001009109

• RNA sequencing of 12 NSCLC samples from 4 patients at MDACC

  Multi-region RNAseq from 4 NSCLC patients, totaling 12 tumor samples and 7 matched control samples.

  Dataset EGAD00001008482

• Single-Cell Data from "Spatiotemporal T-cell tracking for personalized T-cell receptor T-cell therapy designs in childhood cancer"

  This dataset contains the FASTQ files from the Single-Cell GEx+TCR 10X Genomics data from the study "Spatiotemporal T-cell tracking for personalized T-cell receptor T-cell therapy designs in childhood cancer" (EGAS00001008174)

  Dataset EGAD00001015632

• Alopecia and Vitiligo

  exome sequencing data captured with agilent v4 (71k) and sequenced on illumina technology. data from a total of 40 samples, of which 14 are vitiligo cases with familial history of vitiligo or immune disease, and the remaining are alopecia areata cases.

  Dataset EGAD00001005289

• Single-Nuclei RNA-seq of healthy (post-mortem) and temporal lobe epilepsy (biopsy) subjects.

  To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects.

  Dataset EGAD00001006575

• PETAL Network: Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among Inpatients With Symptomatic Disease (ORCHID) Trial

  ORCHID was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US between April 2 and June 19, 2020. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients with five interim analyses; however, the trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.The distribution of the day 14 clinical status score (measured using a 7-category ordinal scale) was not significantly different for patients randomized to receive hydroxychloroquine compared with placebo.Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

  Study phs002299

• IBMsnRNAseq

  snRNA-seq and spatial transcriptomic data and analysis of healthy (CTRL) and inflamed (immune-mediated necrotizing myopathy (IMNM) and inclusion body myositis (IBM)) human quadriceps muscle. This data set includes 19 snRNA-seq (7 CTRL, 4 IMNM, 8 IBM) and 8 ST samples (3 CTRL, 2 IMNM, 3 IBM).

  Dataset EGAD50000000449

• Single-cell RNA-sequencing on malignant and benign tissue samples

  Single-cell RNA-sequencing on malignant and benign tissue samples from untreated donors with colorectal adenocarcinoma and liver metastasis was performed in order to deduce tissue adaptive expression patterns of the disease. Matching tissue from five donors with untreated CRC and liver metastasis were sampled.

  Dataset EGAD50000001203

• Exome data from 154 patients with childhood or adolescent cutaneous melanoma

  This dataset contains sequence data from 154 patients in Australia diagnosed with cutaneous melanoma before the age of 20. Each patient was exome sequenced on the illumina platform. Generated sequence reads were aligned against version 19 of the human genome assembly and stored in bam files made available here.

  Dataset EGAD50000001868

• WGS of multi-centric liver cancers and intra-haptatic metastasis of liver cancer.

  RIKEN collection of WGS read of 59 multi-centric liver cancers or intra-haptatic metastasis and matched blood samples from 19 donors.

  Dataset EGAD00001001643

• Single-cell short-read transcriptomes from CH, MDS and AML patients with splicing factor mutations

  Single-cell RNA sequencing from CH (n = 2), MDS (n = 6, MDS02 in 2 replicates) and AML (n = 1, in 2 replicates) samples with mutations in splicing factors (SF3B1 - n = 8, U2AF1 n = 1). cDNA from 10x Genomics 3' V3.

  Dataset EGAD00001011283

• Italian Primary Biliary Cirrhosis Study

  A Genome-wide association study of primary biliary cirrhosis (PBC) with an Italian cohort and loci meeting suggestive criteria were confirmed using a replication dataset from a previous Canadian study. The results confirmed associations for IL12A, IL12RB2, and HLA (peak between DQA1 and DQB1) and identified novel associations with IKZF3/ORMDL3 on chromosome 17, SPIB on chromosome 19, and IRF5 on chromosome. These studies also provided definition of haplotypic associations, differences between the PBC associated chromosome 17 haplotype and that of pediatric asthma and suggested several other genes as candidates for PBC susceptibility including DENND1B.

  Study phs000444

• "BaTwa" populations from Zambia retain ancestry of past hunter-gatherer groups

  We genotyped and analyzed over two million genome-wide SNPs from two BaTwa populations (40 individuals by population), and from three comparative farming populations (10 to 21 individuals by population) in order to: (i) determine if the Zambian BaTwa carry any genetic material linking them to past hunter-gatherer-groups, and (ii) characterize the genetic affinities of past Zambian hunter-gatherer-groups. We found that both BaTwa populations harbor a hunter-gatherer- like genetic component, representing ∼19% (Bangweulu) and ∼31% (Kafue) of their genetic ancestry, while the rest of their ancestry is similar to western Africans.

  Study EGAS50000000378

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

  Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, <2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.

  Study EGAS00001004510

• COVID_19_UK_CIC_Spatial

  Understanding the immune response to SARS-CoV-2 is critical to our ability to control the coronavirus pandemic. Spatial transcriptomics will be performed on COVID-19 post-mortem tissues in collaboration with the UK - Coronavirus Immunology Consortium (UK-CIC). UK-CIC encompasses a concerted effort by the UK's world-leading immunology community to deliver a co-ordinated and agile national research programme to increase our understanding of how the immune system interacts with SARS-CoV-2. UK-CIC is led by Professor Paul Moss (University of Birmingham) and brings together 20 UK immunology centres of excellence, with support from the British Society for Immunology.

  Study EGAS00001005817

• Clinical utility of combined low-pass whole genome and targeted sequencing in liquid biopsies for diagnosis and monitoring of pediatric solid tumors

  We designed a liquid biopsy (LB) platform employing Low-Pass Whole Genome Sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA isolated from plasma for detecting genome-wide copy number alterations and targeted gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls (patients with non-oncologic diagnoses) and 73 patients, including 44 with bone or soft tissue sarcomas, 12 with renal tumors, 10 with germ cell tumors, 5 with hepatic tumors, and 2 with thyroid tumors.

  Study EGAS00001006913