15017 results for "cancer studies using rna-seq"

in 20.17 milliseconds.

• Characterization of the oral and gut microbiome of melanoma patients before initiation of ant-PD-1 therapy, and confirmation of the phenotype in germ-free mice

  The oral and gut microbiomes of melanoma patients were characterized before the initiation of ant-PD1 immunotherapy, and compared to treatment response. Validation studies were performed in germ-free mice using stool from patients who responded/did not respond to ant-PD1 immunotherapy. All baseline oral(n=86) and gut (n=43) microbiome samples were subject to 16S sequencing - V4 region ( merged fastq files have been made available through this portal). Whole genome shotgun sequencing (WGS) was performed on a subset of fecal samples (n=25)- these files are also available( paired end reads). Also available are 16S sequencing results of stool samples from donors (n=2) used in fecal microbiota transplant and murine samples (n=12) from germ-free mice transplanted with stool from responder/non-responder patients. The fastq files associated with this dataset are stored at ENA under the following links: Fecal 16S – PRJEB22894 https://www.ebi.ac.uk/ena/browser/view/PRJEB22894 Oral 16S – PRJEB22874 https://www.ebi.ac.uk/ena/browser/view/PRJEB22874 Murine 16S – PRJEB22895 https://www.ebi.ac.uk/ena/browser/view/PRJEB22895 Fecal WGS – PRJEB22893 https://www.ebi.ac.uk/ena/browser/view/PRJEB22893

  Dataset EGAD00001003943

• Whole exome sequencing (WES) of EBV- primary central nervous system lymphoma (PCNSL)

  This dataset contains whole exome sequencing (WES) of 29 HIV- EBV- primary central nervous system lymphoma (PCNSL) tumors and 5 activated B-cell-like PCNSL (ABC-PCNSL) and activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) cell lines (TK, HKBML, OCI-Ly3, HBL-1, TMD-8). Cases with secondary involvement of the CNS were excluded. DNA was extracted with AllPrep DNA/RNA FFPE kit and libraries were prepared using the Agilent SureSelect Human All Exon v6 + UTR kit. Paired end reads were aligned to GRCh37 using bwa mem v.0.7.17, and reads were sorted and duplicated were marked in the final BAM files. Access to this data is controlled. There are a number of steps that a researcher must take to obtain access to this data, including execution of a Data Access Agreement between the institutions. The process is overseen by the Technology Development Office; please contact our general email address TDOadmin@phsa.ca. Please only click the "request data" button on the EGA website after a Data Access Agreement is fully executed.

  Dataset EGAD50000000451

• 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

• Dataset for MCPlus_WES

  WES/WGS sequencing data of 75 chromothriptic tumor and control runs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001009276

• The impact of mutational clonality in predicting the response to anti-PD-L1/PD-L1 in advanced urothelial cancer

  The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit. In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.

  Study EGAS00001007086

• Multiomic Landscape of Multiple Myeloma Precursor and Relapsed Disease

  Multiple myeloma (MM) is a treatable, though incurable, plasma cell malignancy. The molecular mechanisms driving disease onset and the emergence of drug resistance remain elusive. To better characterize the mutational, transcriptional, and epigenetic alterations that accompany MM disease evolution, we accessed molecular data from MM patients treated at Moffitt Cancer Center, with bone marrow biopsies collected between 2011 and 2023.We performed scMultiome (single-cell, paired RNA/ATAC-Seq, 10x Genomics) on 18 CD138+-selected bone marrow aspirate samples, including: 2 healthy donors, 3 patients with monoclonal gammopathy of undetermined significance (MGUS), 4 with smoldering myeloma (SMM), 3 with newly diagnosed MM (NDMM), 1 with early relapse MM (ERMM, 1 to 3 lines of therapy), and 5 with late relapse MM (LRMM, 4 or more lines of therapy). Our dataset includes a sequential sample: a patient with a premalignant condition ("scMultiome_SMM_4") that progressed to active myeloma ("scMultiome_NDMM_3"). These data allow for the assessment of transcriptional and epigenetic dysregulation at the cellular level. Our findings illustrate the dynamic epigenetic and transcriptional landscapes that accompany MM disease progression.We also conducted CUT&Tag analysis on 4 NDMM and 4 LRMM samples to map histone modifications, specifically H3K27ac, to investigate their role in transcriptional reprogramming observed in advanced stages of MM. This analysis revealed sample heterogeneity in terms of super-enhancer-regulated genes associated with active transcription.This cohort also includes samples from the clinical trial NCT04151667, “Daratumumab-Based Response-Adaptive Therapy for Older Adults With Newly Diagnosed Multiple Myeloma.” We performed scRNAseq (single-cell RNA sequencing, 10x Genomics) on 30 CD138+-selected bone marrow aspirate samples and 31 pre-sort samples featuring bone marrow mononuclear cells of various cell types from 5 healthy donors and 11 patients with newly diagnosed MM (NDMM). Our dataset includes sequential samples for all 11 NDMM patients, both prior to induction therapy (denoted by ‘a') with Daratumumab and Dexamethasone, and at cycle 2 day 22 (C2D22, i.e., 60 days after induction therapy start, denoted by ‘b'). For three NDMM patients, we also have samples at relapse (denoted by ‘c'). These data allow for the assessment of transcriptional dysregulation at the single-cell level in both the tumor and immune-tumor microenvironment, associated with Daratumumab treatment in NDMM patients.In addition to the molecular data, demographic, and phenotypic information for all samples is provided.

  Study phs003892

• Count Me In (CMI): The Metastatic Breast Cancer (MBC) Project (CMI-MBCproject)

  Count Me In - The Metastatic Breast Cancer Project: A Patient-Driven Research Initiative to Accelerate Metastatic Breast Cancer Research The Metastatic Breast Cancer Project is a research study that directly engages patients with metastatic breast cancer via social media and advocacy groups and empowers them to accelerate cancer research by sharing their samples and clinical information. Our goal is to create a publicly available dataset of genomic, molecular, clinical, and patient-reported data to enable research. Patients in the US or Canada may register online. Registered patients are sent an online consent form that asks for permission to obtain and analyze their medical records, tumor tissue, saliva, and blood samples. Once enrolled, patients are sent a saliva kit and asked to mail back a saliva sample, which is used to extract germline DNA. Study staff contact participants' medical providers and obtain medical records and a portion of their stored tumor biopsies. Patients may be asked to mail in a blood sample, which is used to extract cell free DNA (cfDNA). Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing is performed on tumor RNA. Clinically annotated genomic data are used to study specific patient cohorts (including outliers) and to identify mechanisms of response and resistance to therapies. All de-identified data, including genomic, clinical, and patient-reported data, are shared via public databases on a pre-publication and recurring basis as it is generated. The latest data release in cBioPortal is available here. Study updates are shared with participants regularly.

  Study phs001709

• Next gen seq of eye cancers (2019-08-14)

  Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. The Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms: 1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used. 2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development. 3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies. The aim of this study is to assist finding targeted diagnostic techniques and treatments for RB. . This dataset contains all the data available for this study on 2019-08-14.

  Dataset EGAD00001005251

• Mucociliary Clearance Consortium (MCC) Rare Genetic Disorders of the Airways: Cross-section Comparison of Clinical Features, and Development of Novel Screening and Genetic Test

  We have established a consortium of 7 geographically-dispersed clinical research sites that are designed to study rare diseases of the airways, which involve defects in clearance of mucus secretions from the airways (defective "mucociliary clearance"). These sites will collaborate in diagnostic, genetic, and other studies in patients with impairments of mucociliary clearance, including primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF), and pseudohypoaldosteronism (PHA). These disorders reflect genetic defects in airway host-defense, and typically result in chronic infection of the airways. Patients with these disorders of the conducting airways and sinuses have delayed (or incorrect) diagnoses, because diagnostic tests are not readily available. These patients may also have sub-optimal management of their clinical disease, because the cause of these disorders is not well-defined, and treatment regimens are usually not driven by evidence-based medicine. This current protocol is designed to employ a systematic approach to the diagnostic evaluation of these patients with chronic airways disease, which will yield precise diagnoses in individual patients, and will be associated with development of better diagnostic techniques, including genetic testing. In addition, we will compare/contrast clinical features (phenotype) across these disorders. A rigorous cross-sectional comparison of the clinical features will provide better understanding of the clinical disease of these disorders; in turn, this will lead not only to a better standard of clinical care, but will also assist in the identification of novel therapeutic approaches. The patient population for these studies includes individuals carrying a tentative diagnosis of the three disorders (PCD, variant CF or PHA), plus individuals suspected to have one of these disorders, but with inadequate or inconclusive diagnostic tests. Individuals in this latter category must have a preliminary clinical evaluation to evaluate for other more common disorders that may have similar manifestations including classical CF, immunodeficiency, asthma, and severe gastroesophageal reflux. We have an informal agreement with a network of pulmonologists across the United States to perform clinically-indicated (not research) preliminary clinical testing, if not directly available to patients who inquire about these studies. Blood will be collected for DNA to test for genetic mutations. The blood samples will be processed to establish a cell line (lymphocyte transformation) for a source of DNA for future genetic studies, in participants with disease. For participants unable to provide a blood sample, a buccal sample will be obtained for DNA.

  Study phs000595

• DNA and RNA sequencing of single human haploid germ cells

  Our goal was to look at allele-specific gene expression in single spermatids from two human donors. We first genotyped and phased each donor using a combination of linked-read sequencing (one sample per donor, 10X Chromium), and single haploid whole genome sequencing (53 spermatids for the first donor, and 19 for the second). We then sequenced mRNA from single spermatids (302 from the first donor, and 164 from the second), using the Smart-Seq2 protocol. We used these gene expression data, in combination with the haplotype data, to look for gene products that exhibit allele-specific bias reflecting the haploid genotype of the cell. We find a large class of human genes that show such allele-specific bias in spermatids, indicating that these gene products are not fully shared across the cytoplasmic bridges that connect spermatids. We term these genes “genoinformative markers” (GIMs).

  Study phs002279

• Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid in severe COVID-19 and SARS-CoV-2 stimulated classical blood monocytes

  We analyzed pulmonary monocyte and macrophage responses as well as and pulmonary pathology in two cohorts of patients with COVID-19 associated ARDS. Monocyte-derived macrophages accumulated in the lung during ARDS and acquired a profibrotic signature, characterized by high expression of known fibrogenic factors like TGFB1, SPP1 and LGMN. COVID-19 associated macrophages showed highly significant transcriptional similarity with profibrotic macrophage populations identified in idiopathic pulmonary fibrosis (IPF). Notably, overnight exposure to SARS-CoV-2, but not influenza A virus or viral RNA analogues, induced a similar phenotype in human monocytes from healthy volunteers in vitro. Patients with severe COVID-19 associated ARDS showed clear clinical, radiographic and histopathological features of scarring and fibrotic tissue remodeling. In conclusion, SARS-CoV-2 triggers profibrotic macrophage responses, fibroproliferative ARDS, and lung fibrosis

  Study EGAS00001004928

• Genome-Wide associations of Lung Health Study (LHS)

  The 'Genome-Wide Associations Environmental Interactions in the Lung Health Study' at Johns Hopkins University aims to test for association between lung function decline as a primary outcome associated with chronic obstructive pulmonary disease (COPD) using banked DNA and phenotype data on 4,287 European Americans from the longitudinal, multicenter Lung Health Study (LHS). The broad goals of the LungGO/ESP-GO falls into two general categories: (i) discovery of all variants (i.e., common and rare) in all protein-coding regions of the human genome (i.e., the exome) conferring risk to complex pulmonary diseases including COPD, in a subset of the LHS cohort. The Johns Hopkins University LHS cohort offers a unique opportunity to elucidate genetic variants that cause COPD. The Lung Health Study I was a randomized multicenter clinical trial with 5887 participants carried out from October 1986 to April 1994, designed to test the effectiveness of smoking cessation and bronchodilator administration in smokers aged 35 to 60 with mild lung function impairment. Participants were randomly assigned to one of three groups: usual care, who received no intervention smoking intervention with the inhaled bronchodilator ipratroprium bromide smoking intervention with an inhaled placebo. The effect of intervention was evaluated by the rate of decline of forced expiratory volume in one second (FEV1). For the GWAS, only the subset of European American LHS participants for whom lung function data from three time points or more are available. Thus, the GWAS represents 73% of the 5,887 volunteers who participated in the LHS study. Importantly, LHS subjects included had similar demographics (including age, gender and BMI) and rates of lung function decline (mean annual change in FEV1% predicted: -0.96 %/yr vs. -0.99 %/yr, p=0.57) compared with those not included in the GWAS, reflecting little selection bias for our primary outcome. They were, however, more likely to have quit smoking after 5 years. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to lung function through large-scale genome-wide association studies of smokers enrolled in a multicenter clinical trial. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000335

• North American Mitochondrial Disease Consortium Patient Registry and Biorepository

  Mitochondrial diseases are caused by dysfunction of the mitochondria, which are specialized compartments that are present in every cell of the body except red blood cells. Mitochondria generate more than 90% of the energy that the body needs to sustain life and support growth. When they fail, less and less energy is generated within the cell. This injures the cell and can cause its death. If this process is repeated throughout the body, whole organ systems begin to fail, and the life of the person in whom this is happening is severely compromised. Mitochondrial diseases primarily affect children, but adult onset is becoming more and more common. Mitochondrial diseases are probably the most diverse human disorders at every level: clinical, biochemical, and genetic. Some affect only the nervous system but most affect many body systems, including the brain, heart, liver, skeletal muscles, kidney, and the endocrine and respiratory systems. Although mitochondrial disorders vary in severity, they are usually progressive, and often crippling. They can cause paralysis, seizures, mental retardation, dementia, hearing loss, blindness, weakness and premature death. Because of the range of symptoms and the frequent involvement of multiple body systems, mitochondrial diseases can be a great challenge to diagnose. Even when accurately diagnosed, they pose an even more formidable challenge to treat, as there are very few therapies and most are only partially effective. About this Study The first objective of this study is to establish a clinical registry of patients with suspected or confirmed mitochondrial diseases. We are collecting medical and family history, diagnostic test results, and prospective medical information for these patients and, using agreed procedures developed by the leading research clinicians in the field, providing, for the first time, standardized diagnoses of these complex disorders for the patients. The clinical information we collect from the participants will be used to learn about the spectrum of mitochondrial disorders and their prevalence. We will also develop studies which allow us to better understand how these diseases progress, which we do not understand well enough. When we begin clinical trials for mitochondrial diseases, patients enrolled in the registry who are identified as potentially eligible will be offered enrollment. Patients will only be included in studies if they give their consent in advance. The second objective of this study is to establish a biorepository for specimens and DNA from patients with mitochondrial diseases, in order to make materials easily available to consortium researchers.

  Study phs001538

• Heart Failure Network Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure (HFN IRONOUT-BioLINCC)

  ObjectivesTo test the hypothesis that, compared to placebo, oral iron repletion in heart failure patients with iron deficiency improves exercise capacity after 16 weeks of therapy.Background Iron deficiency affects approximately one half of patients with symptomatic heart failure. The presence of iron deficiency in patients with heart failure is associated with reduced functional capacity, poorer quality of life, and increased mortality. Despite growing recognition of the significance of iron deficiency, randomized multicenter trials exploring the utility of oral iron supplementation, a therapy that is inexpensive, readily available, and safe, have not been performed in patients with heart failure. Moreover, patient characteristics and biochemical profiles that may influence responsiveness to oral iron in patients with heart failure have not been defined. Results of intravenous iron repletion trials have been favorable, but regularly treating patients with intravenous iron products is expensive and poses logistical challenges for outpatients. Therefore, the HFN-IRONOUT study was initiated to investigate the efficacy of oral iron in patients with heart failure with reduced ejection fraction (HFrEF). ParticipantsA total of 225 participants were enrolled, 111 randomized to receive oral iron and 114 randomized to receive the placebo. Design The HFN-IRONOUT study was a phase 2, double-blind, placebo-controlled randomized clinical trial that enrolled participants at 23 sites in the United States. Participants were randomly assigned, in a 1:1 ratio, to receive either oral iron polysaccharide or placebo with the use of an automated web-based system. A permuted block randomization method (with 4 participants per block) was stratified by enrolling site and anemia status (defined as hemoglobin At baseline, 8 weeks, and 16 weeks participants underwent studies including history and physical examination, cardiopulmonary exercise testing (CPET), Kansas City Cardiomyopathy Questionnaire (KCCQ), and 6-minute walk test. CPETs were performed using a 10 Watt/minute incremental ramp protocol and breath-by-breath measures of oxygen uptake were uniformly analyzed by the CPET Core Lab. Participants also underwent phlebotomy for biomarkers. Iron studies, including iron, total iron binding capacity, and ferritin, were measured at baseline and after 16 weeks to determine the extent to which oral iron led to iron repletion. The primary end point was the change in peak oxygen uptake (peak VO2) after 16 weeks of therapy. Conclusions Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks.

  Study phs003557

• Molecular Signature of Saudi Thyroid Cancer Using whole exome sequencing

  In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries also. Differentiated thyroid cancer, which includes papillary thyroid cancer (PTC) and follicular subtypes, accounts for 90% of all thyroid malignancies. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. With the goal of better understanding the pathobiology of thyroid carcinogenesis we will use Whole Exome Sequencing to decipher the molecular and genetic signature of Saudi PTC based on International Cancer Genome Consortium (ICGC) Guidelines. The study will provide a better understanding of PTC and should have important clinical implications in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC

  Study EGAS00001000680

• EXPRESSION OF ANTIBODY-DRUG CONJUGATE TARGETS IN BREAST CANCER METASTASES AND NORMAL TISSUE

  Using bulk mRNA sequencing, we investigated the expression of 72 ADC targets, which are clinically approved or under investigation, in 909 samples (64 primary untreated, 749 metastatic, 96 normal) from 30 female patients from our post-mortem tissue donation program UPTIDER (NCT04531696). The study explores changes in target expression across multiple samples to identify novel targets of clinical interest and validation

  Study EGAS50000001334

• Amplicon_based_sequencing_of_drug_resistant_lung_cancer_cell_lines

  A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature.

  Study EGAS00001001675

• Ultrasensitive Detection and Monitoring of Circulating Tumor DNA using Structural Variants in Early-Stage Breast Cancer

  Circulating tumor DNA (ctDNA) detection has an emerging role in the management of breast cancer, offering a non-invasive means to monitor disease status and detect recurrence. This study demonstrates that longitudinal monitoring of tumor-specific structural variants - frequent alterations observed across many tumor types including all subtypes of breast cancer derived from Whole Genome Sequencing data - allows for ctDNA detection in nearly all participants in this cohort with untreated early breast cancer prior to starting neoadjuvant therapy. On-treatment ctDNA monitoring enabled the early identification of patients at high risk of recurrence and ctDNA was detected prior to relapse in participants across all receptor subtypes. These findings demonstrate the clinical validity of this assay approach for ultrasensitive ctDNA monitoring.

  Study EGAS50000000799

• A super-enhancer associated with CD47 links pro-inflammatory signaling to CD47 upregulation in breast cancer

  CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels in normal cells, however, in cancer cells, CD47 transcript and protein expression is aberrantly increased. Here we sought to uncover the regulators of CD47 transcription, including active enhancers that increase its aberrant expression in cancer cells, in order to reveal mechanisms by which different neoplastic cells generate this dominant 'don't eat me' signal. Enhancers are genomic regions, often referred to as "switches", that can turn on or off the transcription of target genes. Recently the discovery of super-enhancers (SEs) has given more insight into the regulatory architecture of key genes that are highly expressed in a specific cell type, during a particular developmental stage or in disease. By analyzing the CD47 regulatory genomic landscape, we discovered: i) A distinct super-enhancer (SE) is associated with CD47 upregulation in breast cancer cells ii) Disruption of CD47 SEs by using the BRD4 inhibitor JQ1 robustly reduces CD47 gene expression; and iii) The TNF-NFKB1 signaling pathway is directly involved in the regulation of CD47 by interacting with a distal downstream constituent enhancer located within a CD47-associated SE specific to breast cancer. Our results describe a novel mechanism that cancer cells have evolved to drive CD47 overexpression to escape immune surveillance.

  Study phs001264