15174 results for "cancer studies using rna-seq"

in 24.38 milliseconds.

• Whole transcriptome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer

  All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).

  Study EGAS00001004232

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__Targeted_

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003321

• Breast Cancer - Subtype defined by an amplification of the HER2 gene

  Clinically positive HER2 (cHER2+) breast cancers (BC) are defined by the amplification and overexpression of the human epidermal growth factor receptor (HER2/ERBB2) gene on chromosome region 17q12 and represent 15% of all BCs. Although anti-HER2 targeted therapies have improved BC’s natural history, the magnitude of their benefit varies widely between patients and deciphering the genomic heterogeneity of cHER2+ BC may provide a basis to better understand patients’ outcome. As part of the ICGC Breast Cancer Working Group effort, we combined whole genome sequencing and transcriptomic analyses of 64 cHER2+ primary invasive carcinomas.

  Study EGAS00001001431

• Spatial and temporal intra-tumoural heterogeneity in advanced High-Grade Serous Ovarian Cancer: implications for surgical and clinical outcomes

  Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront. Our data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this complexity relates to surgical and clinical outcome and its consequences on clinical decision-making.

  Study EGAS00001007164

• Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.

  CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene independent manner. In contrast, amplifications caused by whole chromosomal duplications have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.

  Dataset EGAD00001004124

• Virginia PrIMeD Study

  The goal of this study was to determine whether screening children (2-16 yrs) in pediatric waiting rooms for genetic risk of type 1 diabetes (T1D) could be applied to diverse (by geography, genetic ancestry) communities, and for those at "high genetic risk," if barriers prevent subsequent screening for presence of islet autoantibodies. A total of 3,818 children were recruited from eight general pediatric and specialty clinics across Virginia. Clinical Research Coordinators were stationed at each clinic and obtained informed consent/assent, a brief medical history, and a saliva sample for DNA extraction and determination of their genetic risk using a T1D Genetic Risk Score (T1D GRS). Children were present in the clinic for a "healthy" visit, although children with and without a history of T1D were recruited into the study. Age, sex, self-reported ancestry/race, T1D history, and other medical history information was obtained. DNA was extracted from the saliva samples and genotyping with a T1D-focused array using 74 SNPs (including 26 SNPs in the HLA region) provided data to generate a T1D GRS for each individual. Of the 3,818 children recruited, there was a slight excess of males (1,959, 51.3%), a majority of white and Hispanic/Latino ancestry (82.8%), and 91 (2.4%) with prevalent T1D. A total of 542 (14.2%) had "high T1D genetic risk" (T1D GRS > 5). Although the T1D GRS included non-HLA genetic variants, 80% of those with "high genetic risk" would have been classified using only those SNPs in the HLA region alone. Of children with "high genetic risk" and without pre-existing T1D (n=494), 7.0% (34/494) consented for islet autoantibody screening. Among children with pre-existing T1D (n=91), 52% (n=48) also had a "high genetic risk." The HLA-focused T1D GRS was not significantly associated with age at onset of T1D. Of those at high genetic risk that consented for autoantibody testing (n=34) and completed the blood collection (n=28), two (2/28, 7.1%) tested positive for multiple autoantibodies and were at significant risk of developing T1D. Follow up of 55% of parents/guardians identified 2 (of 2,096, 0.095%) participants who developed T1D, one at "high genetic risk" and one with a first-degree relative with T1D. A major factor in obtaining islet autoantibody testing was concern over SARS-Cov-2 exposure and an independent non-scheduled blood collection.Individual-level data at each SNP (genotyped and imputed) for T1D genetic risk and affiliated data are provided in dbGaP.

  Study phs003609

• DNA methylomes of monozygotic twins clinically discordant for multiple sclerosis

  Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although genetic susceptibility is important, a modest concordance rate for MS in monozygotic (MZ) twins suggests that interaction with other risk factors is required to develop clinical symptoms. In this study, we examined whether DNA methylation differences contribute to the discordant clinical manifestation of MS in MZ twins, and studied the impact of MS treatments on the DNA methylome. Genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) of 45 MZ twins clinically discordant for MS were generated using the Illumina HumanMethylationEPIC array. Repetitive element methylation and selected differentially methylated positions (DMPs) were validated using targeted deep bisulfite sequencing (TDBS). In addition, we performed whole genome bisulfite sequencing (WGBS) to profile CD4+ memory T-cells of a subset of four MS discordant MZ twins. Our results show that interferon treatment causes robust DNA methylation changes and several epigenetic biomarkers for interferon treatment response were identified. However, overall the PBMC-based methylomes of the MS discordant MZ twins were highly similar, since large systematic methylation differences (>5%) were absent in the data. This suggests that previously reported large methylation changes are probably caused by genetic rather than epigenetic differences. In addition, our data does not support the hypothesis that the observed maternal parent-of-origin effect in MS is due to genomic imprinting errors, and no evidence was found that copy number variations explain the discordant phenotype in these MZ twins. Although not genome-wide significant, a couple of DMPs associated with the MS phenotype were identified and successfully technically replicated using TDBS, including a differentially methylated region (DMR) in the promoter of the transmembrane protein encoding gene TMEM232. Another MS-associated DMP, located in an enhancer in the gene body of the transcription factor ZBTB16, was also associated with medium-term glucocorticoid treatment history. WGBS analysis confirmed this DMP as a promising epigenetic biomarker for glucocorticoid treatment. In conclusion, this epigenome-wide association study (EWAS) in genetically identical twins identified a DMR in the TMEM232 promoter as a candidate loci associated with the clinical manifestation of MS. In addition, epigenetic biomarkers for MS treatments were identified, revealing that not only short-term, but also medium-term treatment effects are detectable in immune cells, which should be taken into account in future EWAS designs.

  Study EGAS00001003147

• Carbamazepine-induced hypersensitivity reactions in Europeans

  An antiepileptic drug carbamazepine is well tolerated by the majority of patients, but can cause severe and potentialy fatal hypersensitivity reactions in a small number of individuals. The aim of this study was to identify genetic predictors of hypersensitivity reactions to carbamazepine. We undertook a genome-wide association study (GWAS) in 22 patients of European ancestry with carbamazepine-induced hypersensitivity syndrome (HSS) and compared our data with genotypes from a healthy population within the WTCCC. We performed imputation of classical HLA alleles according to a recently described method (Science. 2010 Dec 10;330(6010):1551-7. Epub 2010 Nov 4). GWAS statistical analysis was performed using logistic regression with an additive model of inheritance.

  Study EGAS00000000037

• Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS)

  Advances in antiretroviral therapies (ART) and patient management have improved survival of people living with HIV (PLWH). However, with exposure to ART and associated side effects and toxicities as well as to the virus itself, PLWH are at an increased risk of several chronic diseases. The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) research network integrates longitudinal clinical data and treatment management of PLWH and provides research infrastructure to support HIV-associated clinical, social, and behavioral outcomes and comparative effectiveness research using data collected from 8 Centers for AIDS Research clinical sites across United States. For detailed study description, see Kitahata et al. (2008, PMID:18263650).

  Study phs001788

• Children's Hospital of Philadelphia: GWAS of Left-Sided Cardiac Defects

  This is a family-based genome-wide association study of congenital left-sided cardiac lesions (LSLs). Cases with LSLs and their parents were recruited from the Cardiac Center at The Children's Hospital of Philadelphia between 1997 and 2010. The discovery dataset included 405 LSL case-parent triads. DNA was extracted from blood or saliva samples from these subjects and genotyping was conducted using the Illumina Infinium II HumanHap550K array (V3). This study was conducted with approval from the Institutional Review Board for the Protection of Human Subjects of The Children's Hospital of Philadelphia and all research subjects provided either written informed consent or, when appropriate, assent.

  Study phs000781

• Clinical and genetic analysis of retinopathy of prematurity - GWAS

  This project aims to identify genetic variants that contribute to the development of retinopathy of prematurity (ROP). ROP is a leading cause of childhood blindness worldwide. We have performed a genome wide association study (GWAS) using Illumina Global Screening Array (GSA) BeadChip. For this GWAS design we assembled the largest group of ROP patients described to date: around 1000 ROP patients in total. Demographic and phenotypic information associated with each sample includes gestational age, gender, ethnicity, multiple birth status, presence of ROP, and birth weight. The results of this study will help advance our understanding of the genetic susceptibility to ROP and may result in novel treatment options to slow the progression of the disease.

  Study phs002020

• Paired Acute Myeloid Leukemia (AML) Epigenetics Study on Epialleles and Clonality

  We describe methclone, a novel method to identify epigenetic loci that harbor large changes in the clonality of their epialleles (epigenetic alleles). Methclone efficiently analyzes genome-wide DNA methylation sequencing data. We quantify the changes using a composition entropy difference calculation and also introduce a new measure of global clonality shift, loci with epiallele shift per million loci covered, which enables comparisons between different samples to gauge overall epiallelic dynamics. Finally, we demonstrate the utility of methclone in capturing functional epiallele shifts in leukemia patients from diagnosis to relapse. Methclone is open-source and freely available at https://code.google.com/p/methclone. Reprinted with permission from BMC Publishing (Genome Biology).

  Study phs000793

• Phylogenetic Analyses of Melanoma Reveal Complex Patterns of Metastatic Dissemination

  Subpopulations of cells in a primary melanoma can disseminate and establish metastases. Still, the precise ancestral relationship between primary tumors and their metastases is not well understood. Using whole-exome sequencing (for discovery) and targeted sequencing (for validation), we analyzed mutation patterns of primary melanomas and two or more metastases in each of 8 patients to determine their phylogenetic relationships, profiling a total of 31 total tumors. The resulting data show that in 6 of 8 cases, genetically unique cell populations in the primary metastasized in parallel to distinct anatomic sites, rather than sequentially. These data also indicate that individual metastases were sometimes founded by multiple cell populations of the primary that were genetically distinct.

  Study phs000941

• Diabetes Multi-Omic Investigation of Drug Response (DIAMOND)

  The Diabetes Multi-omic Investigation of Drug Response (DIAMOND) cohort is a population-based cohort of individuals with type-2 diabetes (T2D) who receive their care through a large health system serving southeast Michigan and metropolitan Detroit. The cohort represents the diversity of the population from which it was created. Because of their health plan membership, participants have a rich dataset of longitudinal clinical health information related to their care. The intent of the DIAMOND study is to use genomic profiling, drug exposure information, and electronic health record (EHR) derived outcome data to identify genetic predictors of treatment response. Genome-wide genotyping was performed using the AxiomTM Precision Medicine Research Array (ThermoFisher Scientific Inc.).

  Study phs003350

• A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms

  We developed an artificial intelligence (AI)-model applied to histological images using CDH1 biallelic mutations, pathognomonic for breast invasive lobular carcinoma (ILC), as ground truth. We evaluated the performance of the AI-model to predict the presence of CDH1 biallelic mutations and to diagnose ILC. Subsequently, we investigated the molecular underpinning cases of predicted by the model to harbor a CDH1 biallelic mutations but lacking these alterations according to targeted sequencing. Among this analyses, we subjected to whole genome sequencing (WGS) one ILC case lacking CDH1 biallelic mutations by targeted sequencing and lacking CDH1 promoter methylation to determine the molecular basis of its lobular phenotype.

  Study EGAS50000000485

• CpG methylation changes associated with hyperglycemia in type 1 diabetes occur at angiogenic glomerular and retinal gene loci.

  Retinal and glomerular microangiopathy, and cardiovascular disease, contribute to the morbidity and mortality observed in adults with type 1 diabetes (T1D). While the level and duration of hyperglycemia are primary factors influencing these complications, the underlying molecular mechanisms behind glucose-induced organ damage remain poorly understood. In this study, blood samples from young T1D patients at diagnosis and three years later in average were analyzed for DNA methylation using whole-genome bisulfite sequencing. Significant DNA methylation changes in critical angiogenic gene loci were associated with HbA1c, a direct hallmark of chronic hyperglycemia. This finding may offer novel epigenetic insights for a better understanding of T1D complications.

  Study EGAS50000000370

• Lessons learned from the exome sequencing of nine cases of infertility and the way forward

  This study investigated the role of exome sequencing in the diagnosis of male and female infertility. Nine unrelated cases referred between 2019 and 2024 were analysed using exome sequencing, with segregation confirmed by Sanger sequencing and functional assays for splicing variants. We identified nine causative variants in genes including TUBB8, PATL2, CCDC39, STAG3, KIAA0319, FBXO43, AGBL5/BBS7, PLCZ1, and HS6ST1, six of which were novel. The findings highlight diverse reproductive phenotypes such as oocyte maturation arrest, early embryonic arrest, spermatogenic failure, and syndromic infertility. This work demonstrates the value of combining genetic, functional, and clinical approaches to improve diagnostic yield and patient care in reproductive failure.

  Study EGAS50000001320

• The role of gut microbiota in metabolic diseases

  Diabetes is a major disease in the elderly and is responsible for increased risk of myocardial infarction and stroke. Recently, the relationship between microbiota and diabetes has been reported in animals and humans. In this study, blood, stool, and saliva samples were collected from examinees at the University of Tokyo Health Screening Center, and 16S rRNA and metagenomic analyses were performed to determine the variation of microbiota. Furthermore, metabolome analysis and transcriptome analysis (CAGE analysis) using blood were performed to reveal changes in host metabolites and gene expression. By comparing the host- and bacteria- derived information with the metabolic parameters, we analyzed whether microbiota can be a predictor of metabolic diseases.

  Study JGAS000569

• Human periportal liver assembloids recapitulate periportal liver tissue in vitro

  In vitro expansion of human hepatocytes from fresh patient tissues has not yet been achieved, limiting the possibility of modelling liver composite structures in vitro. Here, we developed human hepatocyte organoids from patient-donors that sustain the long-term expansion of hepatocytes in vitro. We profiled them using RNAseq to determine their gene expression pattern and compared this with the original native fresh isolated liver cell. Then, we used them to generate periportal liver assembloids by combining them with portal mesenchyme and cholangiocyte organoids. By increasing the number of mesenchymal cells we obtained structures with a fibrotic ratio of portal mesenchyme and we performed scRNAseq analysis to determine their gene expression and cell-cell interactions.

  Study EGAS50000000994

• Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability

  Intellectual disability is a common condition that carries lifelong severe medical and developmental consequences. The causes of intellectual disability (ID) remain unknown for the majority of patients due to the extensive clinical and genetic heterogeneity of this disorder. De novo mutations may play an important role in ID as most individuals with ID present as isolated cases without family history and/or clear syndromic indication. In addition, the involvement of such mutations have recently been demonstrated in a small number of individuals with ID. Here we evaluate the diagnostic potential and role of de novo mutations in a cohort of 100 patients with ID of unknown cause using family-based exome sequencing.

  Study EGAS00001000287

• Whole-genome-Sequencing of adult medulloblastoma

  Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.

  Study EGAS00001000393

• Proteomic Characterization of Intrahepatic Cholangiocarcinoma Identifies Risk-Stratifying Subgroups, Proteins Associated with Time-To-Recurrence, and mTOR Effector Molecule EIF4A1 as a Druggable Therapeutic Target

  Using mass spectrometry-based proteomics, we analyzed two independent cohorts comprising 80 and 62 treatment-naive ICC tumors, 67 adjacent non-malignant tissues, and 9 patient-derived xenografts (PDX). In the first cohort, we identifed two subclusters with distinct times-to-recurrence (TTR). A 4-protein classifier trained on our data cohort accurately stratifies these ICC clusters in the Dong et al. dataset (2022) and in our independent second cohort, revealing similar associations between proteomic motifs and clinical outcomes. The Translation regulator EIF4A1 emerges as a therapeutic target, as its inhibition with novel drug eFT226 significantly reduces tumor growth in an ICC PDX model.

  Study EGAS50000001343

• STREP GENE: Genetics and Severe Streptococcal Infections

  This study investigated host genetic susceptibility to invasive group A streptococcal disease in the UK. Cases were either survivors recruited retrospectively through a patient group or identified from the a tissue bank at Imperial College London. Those recruited through the patient group had survived an episode of invasive GAS disease at a UK hospital since 1980 with microbiological confirmation obtained either through Public Health England or from the treating hospital. Those identified from the tissue bank had been diagnosed with invasive GAS disease at the Hammersmith Hospital, London, UK, since 2006. All cases aged less than 65 years without long-term medical conditions genome-wide genotyped using either the Illumina HumanCore or the Global Screening Array platform.

  Study EGAS00001003421

• Comprehensive analysis of the (epi)genome of pediatric atypical teratoid/rhabdoid tumours (AT/RTs)

  Whole exome sequencing of atypical teratoid /rhabdoid tumors (AT/RTs) revealed recurrent mutations only in SMARCB1, a gene involved in chromatin remodeling. However, preliminary data from our lab using gene expression and DNA methylation arrays shows that there are three distinct molecular subgroups of AT/RTs, suggesting that other molecular alterations underlying the development of these aggressive pediatric brain tumors must be found outside the coding genome or at the epigenomic level. Identification of these (epi)genomic alterations, which we intend to address in this project, may lead to novel treatment strategies for these tumors and reveal options for meaningful patient stratification.

  Study EGAS00001001297

• Identifying causative mutations for Thrombocytopenia with Absent Radii

  Thrombocytopenia with Absent Radii is an inherited disorder that manifests itself with major limb skeletal abnormalities and low platelet count (and therefore a bleeding diathesis). The syndrome is well-characterised and defined phenotypically and there is a well-established database of UK-based families affected with ths disorder. The causative mutation for the disorder is yet to be identified. If known, it would allow for pre-natal screening and counselling avoiding life-long care for patients who are affected and are therefore severely disabled. We postulate that exon sequencing of 4 unrelated affected individuals would give enough power to narrow down potential candidate mutations which would thereafter be confirmed using DNA from other affected families.

  Study EGAS00001000054