13384 results for ""60+mice"+"6+weeks"+diet+study+2014+2017+DOI"

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• Analysis of mechanisms of CD19- relapse following novel low affinity CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in a Phase I clinical study in paediatric ALL: CARPALL

  Phase I clinical study (CARPALL, NCT02443831) utilizing a novel low affinity CD19CAR CAR in patients age <25 with high risk CD19+ ALL. Seventeen patients were enrolled and 14 received an infusion of CAR T cells. Among those achieving complete remission, 6 subsequently relapsed, 5 with CD19- disease, 1 with CD19+ disease. Whole exome sequencing of bone marrow DNA from patients with CD19- relapse showed mutations in the CD19 gene predicted to result in loss of surface expression in 4/5 patients. These mutations were not detectable prior to CAR T cell therapy. With a median follow-up of 14 months, 5/14 patients (36%) are alive and disease-free. Overall survival was 84% at 6 months and 63% at 12 months and by the criteria used in the ELIANA study, event-free survival was 67% and 46%. Using more stringent criteria where an event is defined as molecular relapse, molecular EFS was 55% and 29 %. The median duration of remission in responding patients was 7.4 months.

  Study EGAS00001003733

• This study explored and validated the clinical application of targeted NGS of circulating tumor DNA in identifying tumor-specific mutations and uncovering clinical actionable targets in a variety of solid tumors in large patient cohorts.

  Cancer is a disease of genetic alterations. Comprehensive genetic diagnosis is needed to match each patient to appropriate cancer therapy. However, acquisition of representative tumor samples is invasive and often infeasible. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for cancer mutational profiling. Here we implemented targeted next generation sequencing (NGS) with a customized pan-cancer gene panel on 605 clinical ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients have at least one clinical actionable mutation with 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients, which could be used to guide treatment decision and monitor the appearance of drug-resistant mutations. Taken together, our study demonstrated the clinical utility of target NGS-based ctDNA mutational profiling to guide cancer treatment decision.

  Study EGAS00001002251

• Molecular Sub-grouping of CNS-PNET

  In our study we aimed to define CNS-PNET subgroups. We performed Expression, Genotyping and/or Immunohistochemistry on 142 samples from 20 worldwide centers. Using these techniques, we have identified three molecular subgroups with distinct expression and copy number patterns, as well as, unique clinical characteristics. Specifically, these molecular subgroups were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Our report underscores the importance of concerted, collaborative efforts to study large retrospective cohorts of tumours and patients to accelerate biological and ultimately therapeutic studies of rare tumours. The outcome of such a collaboration allowed us to identify LIN28 and OLIG2 as promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.

  Study EGAS00000000116

• Differential Gene Expression in Cryptorchid Testes

  Differential Gene Expression in Cryptorchid Testes Study uses whole-genome RNA profiling of testicular biopsies to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA-sequencing (RNA-seq). Fifteen patients were selected based on the histological results and were divided into two groups. Seven were classified as belonging to the high infertility risk (HIR) and eight to the low infertility risk (LIR) group. Cryptorchid boys in the high infertility risk group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini puberty. This group of patients will be infertile despite successful surgery.

  Study phs001275

• Center for Common Disease Genomics [CCDG] - Cardiovascular ATVB: Atherosclerosis Thrombosis and Vascular Biology

  Italian Atherosclerosis Thrombosis and Vascular Biology study is a prospective, nationwide, case-control study involving 125 coronary care units in Italy. The cases were patients who were hospitalised for a first MI before the age of 45 years and underwent coronary angiography. Acute MI was defined as resting chest pain lasting more than 30 minutes, accompanied by persistent electrocardiographic changes, and confirmed by an increase in total creatine kinase or in the MB fraction to more than twice the upper normal limits. The controls were healthy subjects without a history of thromboembolic disease who were unrelated to the patients, but individually matched with them by age, gender and geographical origin. They were enrolled from among the blood donors or staff of the same participating hospitals. Recruitment of cases and controls took place between 1994 and 2007. This site hosts data from ~60 whole exomes.

  Study phs001592

• Natural History of and Genetic Modifiers in Spinocerebellar Ataxias

  Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCA and this study will focus on types 1, 2, 3, and 6 (SCA 1, SCA 2, SCA 3, also known as Machado-Joseph disease and SCA 6). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease. The research questions are: How does the disease progress over time? What are the best ways to measure disease progression? Do some genes, other than the gene that is abnormal in the SCA disease, have any effect on the way the disease behaves?

  Study phs001332

• Genetic Analysis of Psoriasis and Psoriatic Arthritis: GWAS of Psoriatic Arthritis

  This study is a genome-wide study of genetic associations with psoriatic arthritis (PsA), an inflammatory musculoskeletal condition that develops in up to 30% of people who have chronic psoriasis skin lesions. 1,526 cases affected with psoriatic arthritis and 1,508 unaffected controls were recruited and typed on the Illumina HumanOmni1-Quad BeadChip array. After application of quality control measures to both samples and SNPs, genotypes for 791,217 autosomal SNPs were available for 1,430 PsA cases and 1,417 controls. Imputation using phased haplotypes for the EUR subpopulation of release 3, phase 1 of the 1000 Genomes Project as a reference, resulted in genotypes for 11,532,644 SNPs and 918,976 indels passing our imputation quality threshold (Mach r2 ≥ 0.3) that were available for downstream analysis. Association at a genome-wide threshold of significance was found for five regions (near genes TNIP1, IL12B, HLA-C, TRAF3IP2, and TYK2).

  Study phs000982

• The CHOP Pediatric Genetic Sequencing (PediSeq) Project : Applying Genomic Sequencing in Pediatrics

  The purpose of this research study is to learn more about newer types of genetic testing called whole exome sequencing and whole genome sequencing. Current genetic testing usually examines one gene or a few genes at a time. Exome and genome sequencing allow us to test most of a person's genes at one time with a single test. This testing might identify the reason for a person's unexplained condition or diagnosis. We hope this study will help us identify the best methods for: Educating patients and families about exome and genome sequencing Analyzing exome and genome sequencing data to identify results relevant to patients Giving results to families in a clear, appropriate, and informative manner The current data only includes WES for 159 samples. The WGS samples for 20 samples will be uploaded in the near future.

  Study phs000935

• Center for Common Disease Genomics (CCDG) - Cardiovascular: eMERGE - Northwestern Cohort

  The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases. This study contains variant calls derived from the whole genome sequence data of an early-onset coronary artery disease case-control cohort selected from the NUgene Project biobank at Northwestern University. Case status was assigned based on the presence of myocardial infarction, coronary artery stenosis greater than 70% in at least one coronary artery, and/or revascularization (coronary angioplasty with or without stent placement or coronary artery bypass grafting) at an early age. In this study "early age" is defined as men 60 years of age or younger and women 70 years of age or younger.

  Study phs001913

• PLCO - Limited Use Pilot Test Data

  This is a sample of Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial data for limited use in a pilot test for remote data access. The PLCO is a randomized, controlled trial of screening tests for prostate, lung, colorectal and ovarian cancers. Approximately 155,000 participants were enrolled between November 1993 and July 2001. Participants were individually randomized to the control arm or intervention arm in equal proportions. Participants assigned to the control arm received usual care, whereas participants assigned to the intervention arm were invited to receive screening exams for prostate, lung, colorectal and ovarian cancers as outlined in the study protocol. The goal of the study was to assess whether these screening exams reduce mortality from prostate, lung, colorectal and ovarian cancers. Data were collected on cancer diagnoses and deaths from all causes that occurred through December 31, 2009. Median follow-up time was 12.4 years.

  Study phs002011

• Combinatorial Indexed 10x Genomics Single-Cell ATAC-seq on Human Cerebral Cortex

  Single-cell chromatin accessibility profiling (scATAC) using droplet fluidics (10x Genomics) is inherently limited in throughput due to the number of available indexed droplets. This study leverages single-cell combinatorial indexing workflows with modified adapter designs to enable indexed tagmentation and superloading of pre-indexed nuclei into the 10x Genomics scATAC workflow, enabling a substantial increase in the number of cell profiles that can be obtained per channel. This workflow, 10x single-cell combinatorial indexed ATAC-seq (txsciATAC), is demonstrated on human brain tissue (middle frontal gyrus), along with mouse brain tissue to enable doublet and crosstalk assessment. This study includes all human data and includes a single preparation taken through nuclei isolation and indexed tagmentation using 96 indexes then split to produce two datasets, one targeting 20k cells and one targeting 70k, each using a single channel of the 10x Chromium controller.

  Study phs003497

• Combined PDCD1, BRAF and MAP2K7 Inhibition in BRAFV600E Colorectal Cancer: A Phase 2 Trial

  In this study, we evaluated the clinical efficacy of combined PDCD1, BRAF, and MAP2K7 inhibition in metastatic BRAFV600E Colorectal Cancer (CRC) patients (NCT03668431). We performed bulk whole exome sequencing (WXS) and bulk RNA sequencing (RNA-Seq) in 35 pre-treatment tumor biopsies and matching germline for tumor mutational burden (TMB), BM1/BM2 transcriptional subtypes, and consensus molecular subtypes (CMS) analysis, which were previously reported to affect prognosis and response to therapy (PMIDs: 32047001, 27354468, and 26457756). Analysis of bulk data showed that TMB, BM1/BM2 subtypes, and CMS did not correlate with clinical response in this study. Analysis of single cell RNA sequencing (scRNA-Seq) data of tumor epithelial cells from 23 paired day 0 and day 15 tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome.

  Study phs003178

• NHLBI TOPMed - NHGRI CCDG: Genes-Environments and Admixture in Latino Asthmatics (GALA II)

  This is a case-only pharmacogenetic study of bronchodilator drug response among racially admixed Latino children with asthma. Each participant had two spirometry measurements using the KoKo PFT System. With the first spirometry test, participant was administered with 4 puffs of HFA Albuterol. The second albuterol measurement was based on age, for participants under 16 years of age, additional 2 puffs were administered and for those over 16 years of age, additional 4 puffs were administered. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants are 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications. Comprehensive phenotypic data for GALAII study participants are available through dbGaP phs001180.

  Study phs000920

• Whole-genome sequencing of BRCA-mutant breast cancer patient samples from tumour, germline tissue and plasma

  The use of circulating tumor DNA (ctDNA) to profile mutational signatures presents a non-invasive opportunity for understanding cancer mutational processes. In this study we developed MisMatchFinder, a liquid biopsy approach for mutational signature detection using low- coverage whole-genome sequencing of ctDNA. Through analysis of plasma samples across multiple different cancers, we demonstrated that MisMatchFinder accurately infers single-base and doublet-base substitutions as well as indels to enhance detection of ctDNA and clinically relevant mutational signatures. This study contains fastq files from whole-genome sequencing of temporally matched tumour (fresh frozen biopsies), blood germline and plasma samples collected from a BRCA1-mutant breast cancer patient to directly compare mutation signature analysis using gold-standard tumour-germline paired variant calling with our novel ctDNA-based method (MisMatchFinder).

  Study EGAS50000000569

• Genomic Sequencing of Ewing Sarcoma

  Pediatric Ewing sarcoma is a pediatric cancer that primarily arises from the bone. It is characterized by chimeric fusions of the EWS gene and an ETS family transcription factor. In this study, we performed massively parallel sequencing of a larger collection of Ewing sarcoma tumors to define the genomic landscape of this disease. We found that these tumors are among of the most genetically normal cancers currently characterized. There was also a marked absence of recurrent mutations in immediately targetable signaling transduction pathway genes. In this study we answer outstanding questions about ETS transcription factor expression, effects of treatment on mutational burden in Ewing sarcoma tumors, and describe patterns of tumor evolution. We also found that loss-of-function mutations in STAG2 were present in approximately 15% of Ewing sarcoma tumors and loss of STAG2 expression was associated with disease metastasis in this patient cohort.

  Study phs000804

• SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population

  The SweGen project represents a comprehensive map of genetic variation in the Swedish population. This Study contains four datasets where the first one contains whole-genome sequencing data in CRAM-format for 942 individuals from the Swedish Twin Registry, the second one contains genetic variant frequencies in VCF-format for the same individuals, the third one contains whole-genome sequencing data in CRAM-format for 58 individuals from the Northern Sweden Population Health Study and the fourth one contains genetic variant frequencies in VCF-format for the same individuals. The data, serving as a reference dataset, is a valuable and national resource for genetics research and clinical diagnostics and can be used, for instance, to increase understanding of both rare and complex disorders. It also serves as an international resource for larger studies of human population genetics.

  Study EGAS50000000906

• Dysregulation of Alternative Splicing Is a Transcriptomic Feature of Patient Derived Fibroblasts From CAG Repeat Expansion Spinocerebellar Ataxias

  The aim of this study was to characterize transcriptomic changes in patient-derived cell lines of CAG repeat expansion spinocerebellar ataxias (SCAs), using RNA-sequencing (RNA-Seq), to help us better understand disease pathogenesis. The data consists of two SCA1, two SCA3, and one SCA7 cell lines with 5 unaffected controls. Widespread alternative splicing dysregulation was identified across all SCA cell lines. Alternative splicing analysis also revealed that the dysregulation affected disease-relevant pathways with novel skipped-exon splicing events from the RNA-Seq data validated with RT-PCR. These findings are consistent with a previous study that identified robust transcriptomic dysregulation, specifically at the splicing level, in SCA1, -3, and -7 mouse models even at presymptomatic ages. Therefore, alternative splicing has the potential to be used as a biomarker not only in mouse models, but also patient models of repeat expansion SCAs.

  Study phs003759

• Exome sequencing of samples taken at multipl time points to monitor therapy response in AML

  As part of our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory AML patients based on exome sequencing and ex-vivo drug sensitivity and resistance testing data. In this study, we developed this approach further to take into account clonal heterogeneity and analyzed responses of 13 AML patients to chemotherapy and six patients to targeted treatments by using exome and ultra-deep amplicon resequencing. The data submitted includes fastq files from exome sequencing of multiple time-point samples collected from the 13 patients. In this study we identified rare subclonal variants present at diagnosis or later relapse samples and developed a correlation-based method to compare subclonal responses in serial samples across multiple time-points. Significant subclone-specific responses were observed subsequent to chemotherapy and specifically to targeted therapy in five patients.

  Study EGAS00001001948

• T2D-GENES: Exome sequencing

  The Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) is a large collaboration effort between the University of Michigan, Broad Institute, the Wellcome Trust Centre for Human Genetics, University of Chicago, NIDDK, Texas Biomedical Research Institute, University of Texas Health Science Center, University of North Carolina, Blood Systems Research Institute, and University of Mississippi Medical Center. The goal of this study is to identify genetic variants for type 2 diabetes through multiethnic sequencing studies. In this study, we use next generation sequencing to assess the role of common, low frequency, and rare variants on type 2 diabetes risk. We preformed exome sequencing in 6,546 T2D cases and 6,457 control individuals of multiethnic origin, including individuals of African American, East Asian, South Asian, Hispanic, and European descent.

  Study EGAS00001001460

• RNA-seq, WGS and WES of Hepatocellular carcinomas, enriched in fibrolamellar carcinomas

  DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.

  Study EGAS00001003837

• RNA-sequencing data from 195 B-cell precursor acute lymphoblastic leukemias and mate pair whole genome sequencing data from 15 B-cell precursor acute lymphoblastic leukemias

  Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Using RNA-sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a new subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene expression profile and coexisting ETV6 and IKZF1 alterations. Taken together, this study provides a detailed overview of fusion genes in pediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide novel therapeutic options in this disease.

  Study EGAS00001001795

• Genome-wide DNA methylation profiles by MeDIP-seq of cord blood cells and cord blood mononuclear cells obtained from twins conceived through in vitro fertilization and naturally conceived controls

  The study included 47 newborn twins conceived though in vitro fertilisation (IVF) and 60 non-IVF-conceived twins from the Peri/postnatal Epigenetic Twins Study (PETS). Cord blood was collected at birth and used to process mononuclear cells. Whole blood cells (WBCs) from cord blood of 98 twins (40 IVF and 58 non-IVF) and cord blood mononuclear cells (CBMCs) of 82 twins (35 IVF and 47 non-IVF) were subjected to DNA methylation profiling. Methylated DNA immunoprecipitation followed by deep sequencing (MeDIP-seq) was applied to generate genome-wide DNA methylation profiles in a total of 180 samples. Single-end reads were mapped onto hg19 using BWA. Methylation levels were quantified using MEDIPS and used to identify IVF-associated differentially methylated regions.

  Study EGAS00001002248

• Ongoing_mutagenesis_RNAseq

  One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest were selected, subcloned over a defined period of time and their genomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. To further study the recent observation that some of the clones belonging to a same cell line acquired differencet numbers of mutations over a set period of time, their RNA will be subjected to RNA-sequencing to study their differences.

  Study EGAS00001002364

• Therapeutic Targeting of Ependymoma as Informed by Oncogenic Enhancer Profiling

  Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Here, we mapped active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and slowed proliferation in mouse and neurosphere patient-derived models of ependymomas. This study represents one of the largest enhancer mapping study of any cancer type to date, and provides a framework for target and drug discovery for other cancers recalcitrant to therapeutic development because of their lack of known genetic drivers.

  Study EGAS00001002696

• Autozygosity_pilot___British_Pakistani_from_Birmingham_2

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Study EGAS00001000567