1217 results for ""initial+cohort"+"mid-2020s"+"consortium"+"scholarly+exchange"+"university""

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• Skin Microbiome in Disease States: Atopic Dermatitis and Immunodeficiency

  The NIH Intramural Skin Microbiome Consortium (NISMC) is a collaboration of investigators with primary expertise in genomics, bioinformatics, large-scale DNA sequencing, dermatology, immunology, allergy, infectious disease, and clinical microbiology. Atopic dermatitis (AD, "eczema") is a chronic relapsing skin disorder that affects ~15% of U.S. children and is associated with $1 billion of medical costs annually. AD is characterized by dry, itchy skin, infiltrated with immune cells. Colonization by Staphylococcus aureus (S. aureus) is ten-fold more common in AD patients and is associated with disease flares. We hypothesize that, in addition to S. aureus, AD may also be associated with additional novel microbes and/or selective shifts of commensal microbes that are relevant to disease progression. The NISMC seeks to define the microbiota that resides in and on the skin and nares of three patient groups, all of whom have eczematous lesions and are currently seen at the NIH Clinical Center: (1) AD patients; (2) Wiskott-Aldrich syndrome (WAS) patients; and (3) Hyper IgE syndrome (HIES) syndrome patients. Examination of the microbiome of patients with WAS or HIES syndromes, both rare immunodeficiencies, will advance our understanding of how an individual's immune system shapes their cutaneous microbial community. We are performing a prospective longitudinal study that follows these groups of patient thorough the cycles of eczema flares, ascertaining clinical data and samples at each stage.

  Study phs000266

• North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES)

  North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. Participants are patients who were either seen in the UNC Cancer and Adult Genetics Clinic or referred to the study by their physician. They will be approached by their physician or a genetic counselor for recruitment. Once enrolled, a clinical geneticist or genetic counselor will obtain consent and collect blood samples to be analyzed using WES. Results may include information related to a diagnosis and incidental information. Medically actionable incidental findings will be CLIA-certified and returned to participants in a routine genetic counseling session, along with diagnostic findings. Eligible adult participants will be randomized to have the opportunity to choose to get certain types of non-medically actionable incidental findings, as well. Their decisions will be investigated, as will psychosocial and behavioral responses to sequencing and receiving sequencing information. This is a longitudinal, mixed methods study (i.e., multiple assessments pre- and post-return of results, with both quantitative and qualitative methods used to gather data). Because only the quantitative component of the study uses randomization, only measures and procedures associated with that component are included here. The third study release includes data of additional n=189 subjects.

  Study phs000827

• BRAIN Cell EncyclOpeDia of Transcribed Elements (BRAINcode)

  BRAINCODE: How Does the Human Genome Function in Specific Brain Neurons? The human brain comprises about 86 billion neurons whose function is central to human biology. How does the human genome program high performing neurons and neural networks in response to experience? What subprograms does the genome express in physiologically and morphologically distinct brain cells? The goal of the BRAIN Cell encyclOpeDia of transcribed Elements Consortium (BRAINcode) is to provide a map of gene expression - both protein-coding and non-coding - in specific cell types, not in culture, but in situ in brains of people. Going beyond traditional mRNA sequencing, polyadenylated and non-polyadenylated transcripts were ultra deeply sequenced using ribo-depleted RNA from neurons laser-captured from human post-mortem brains. Three prototypical neuron types, dopamine neurons, pyramidal neurons, and Betz cells, were prioritized because of their key biologic roles and differential vulnerability to important neurodegenerative diseases such as Parkinson's or Alzheimer's disease. Genetic variation between individuals was examined for correlation with differences in transcribed sequences to identify regions of the genome that influence whether, how, and how much a transcript is expressed in specific cell types in human brains. Our results indicate a vast universe of annotated and novel non-coding RNAs expressed in brain cells and suggest a more diverse and much more complex transcriptional architecture than previously imagined.

  Study phs001556

• Aurora US Metastatic Breast Cancer Retrospective Project

  The AURORA US Metastatic Breast Cancer project is funded by the Breast Cancer Research Foundation (BCRF) Evelyn H. Lauder Founder's Fund for Metastatic Breast Cancer Research. This multi-center effort conducted within the Translational Breast Cancer Research Consortium (TBCRC) and cancer researchers to better understand the metastatic process through the study of both the primary and metastatic tissue. In the retrospective phase, TBCRC sites submitted matched primary and metastatic tissues and blood from previous collections for piloting the process. Samples were profiled using whole genome DNA sequencing, whole exome DNA sequencing, DNA methylation arrays, and RNA sequencing. The final freeze set for samples with successful nucleic acid extraction and molecular assays included 55 patients with 31 primary tissues and 102 metastases. Twenty patients had tissue collected at autopsy and included 19 with more than one metastasis. Metastases were from 20 different tissue locations with the most common sites being liver, lung, lymph node, and brain. The median age at primary diagnosis was 49 years. The clinical subtypes of the primary tumors were 34% Triple Negative, 30% ER+HER2-, 11% ER+HER2+, and 7% ER-HER2+. Patients received an average of 3 lines of therapy in the metastatic setting. The median overall survival from primary diagnosis was 4.5 years and overall survival from metastatic diagnosis was 2 years.

  Study phs002622

• Epigenetic profiling of human CD4+ memory T cells reveals their proliferative history and argues in favor of a progressive differentiation model driven by epigenetically controlled master regulators.

  A key element of adaptive immunity is the development of long-lived memory cells, which protect against recurring infection by providing a highly enriched pool of antigen-specific cells ready to react to the pathogen. Different classes of memory T cells occur upon primary activation of naive T cells, however, their detailed differentiation pathway is not entirely clear. As part of the IHEC consortium, we generated genome-wide epigenetic maps of a number of CD4+ T cell memory (Tmem) stages including rare subsets such as terminally differentiated (TEMRA) and bone marrow-resident Tmem. We found that CD4+ T cells show progressive global DNA demethylation with differentiation into memory stages, which reflects their proliferative history and likely indicates their decline in differentiation and proliferation potential. Furthermore, transcriptomic profiling combined with co-regulation network analyses arranged different Tmem subsets into a successive differentiation pathway. In addition, we identified a number of epigenetically controlled candidate master regulators for Tmem formation, of which we functionally validated a new methylation-sensitive promoter for the known 'naive-keeper' transcription factor Foxp1. Our study highlights the power of epigenomic datasets in the elucidation of the cellular history but also of the functional potential of T cell populations including the identification of epigenetically controlled master regulators.

  Study EGAS00001001624

• Myocardial Infarction Genetics Exome Sequencing Consortium: Malmo Diet and Cancer Study

  The Malmo Diet and Cancer Study (MDCS) is a community-based prospective epidemiologic cohort of 28,449 subjects who were recruited for baseline examination between 1991 and 1996. From this cohort, 6103 subjects were randomly selected to participate in a cardiovascular cohort (MDCSCC), which seeks to investigate risk factors for cardiovascular disease. This study is a subset of those samples. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Illumina's ICE Capture reagent and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs001101

• TSO500 STJAN33, BRAF mutated CUP

  The data set contains FASTQ files (filetype) of a NEXTSEQ550DX run (instrument). De FASTQ files are from DNA and RNA sample. The Library prep is a NGS TSO500 library prep (Illumina) (technology). A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre (BALLETT) This 2-year study involves the consortium of 9 cooperating Belgian NGS laboratories and will enroll 936 metastatic or locally advanced cancer patients coming from 13 different Belgian hospitals and cancer centers. Upon inclusion, all cancer patients will be offered 'comprehensive genomic profiling' (CGP) using Illumina's TSO500 NGS panel. This targeted NGS panel of 523 genes allows for the detection of single nucleotide variants, small indels, copy number variations and fusions, as well as for the determination of the 'tumor mutational burden' (TMB) and the 'microsatellite-instability' status (MSI). Both the wet lab execution of the CGP as well as the biological and clinical classification of the variants will be performed in a fully standardized way among the 9 participating Belgian local NGS laboratories.

  Dataset EGAD50000000689

• Singapore Gastric Cancer Consortium GeoMx DSP tissue microarray (SGCC TMA) cohort

  Gastric cancer (GC) remains a significant global health challenge due to its high heterogeneity, with intratumoral heterogeneity (ITH) posing a major obstacle to effective patient outcomes. In this study, utilizing GeoMx Digital Spatial Profiler (DSP) technology, we specifically investigated ITH within GC patients by comparing tumor core regions to tumor edge regions. Our findings indicate that tumor edge regions exhibit more advanced tumor activity, akin to the G2-like progressed state, compared to tumor core regions. The findings confirm the spatial locations of G2 RNA-ITH subregions and support the conclusions drawn from the discovery cohort.

  Study EGAS50000000640

• A Multiethnic Genome-wide Scan of Prostate Cancer

  Multiple GWA studies of prostate cancer conducted in European White populations are ongoing. These studies will continue to have a dramatic impact on our understanding of the contribution of common genetic variation on inter-individual susceptibility to this common cancer. Important questions that will remain unanswered, however, are whether all common risk alleles for prostate cancer will be revealed in studies limited to populations of European ancestry. A comprehensive examination of common genetic variation in men of Japanese, Latino, and African ancestry will be required to understand population differences in disease risk and to reveal the full spectrum of causal alleles that exist in these populations. Further, genetic and environmental diversity is likely to contribute to ethnic heterogeneity of genetic effects. Elucidating gene x gene and gene x environment interactions is also likely to provide knowledge that may be critical for understanding the contribution of genetic susceptibility to racial/ethnic disparities in prostate cancer incidence and for translating the findings from GWA studies into interventions. In this study we plan to undertake a genome-wide association study (GWAS) of prostate cancer in the Multiethnic Cohort (MEC) Study. We propose the following hypotheses: (a) that inherited DNA variation influences risk of prostate cancer; (b) that many of the causal alleles will be outside known "candidate genes" requiring an agnostic, comprehensive search; and (c) that performing this search in a multi-ethnic cohort is more powerful than a study limited to a single population to reveal the full range of causal alleles relevant to the U.S. population. The version 1 release of this dataset will include genotype data for the Japanese and Latino populations in the study. The version 2 release will include data for the African ancestry population along with the Japanese and Latino subjects. The version 3 release will include fully-cleaned genotype data for all three populations. 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 prostate cancer through large-scale genome-wide association studies of a well-characterized multi-ethnic cohort. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center and at the University of Southern California. Data cleaning and harmonization were performed at the GEI-funded GENEVA Coordinating Center at the University of Washington. As an add-on to this GWAS we performed a targeted re-sequencing of all known prostate cancer risk loci in the samples from the MEC. Sequencing was performed in Dr. Reich's lab at Harvard Medical School.

  Study phs000306

• NIDA Genetic Epidemiology of Opioid Dependence in Bulgaria (GEODB)

  The study was conducted in Bulgaria as a collaboration between the Molecular Medicine Center (Medical University, Sofia), the Bulgarian Addictions Institute (Sofia), the Initiative for Health Foundation (Sofia) and Washington University School of Medicine (Saint Louis, MO, USA). This is a case-population control study. Participants (N=2,499 interviews; N=1,995 with GWAS data) in our study are primarily active heroin users (78%) aged 18 and over, with a median 8.9 years of daily heroin use (minimum of 12 months). Virtually all participants (99.1%) qualified for a lifetime DSM-IV diagnosis of dependence, symptom endorsement probabilities ranging from 77% to 99.3%; and 61% endorsing all symptoms. 85% were heroin injectors and 97% reported using (or having used) heroin daily. Anonymized, population-representative control samples (no phenotypic data, N = 1,062 with GWAS data) were drawn from the MMC repository. Unlike other studies, where samples are clinically ascertained (e.g., from ORT programs), our participants are primarily untreated. PTSD, major depression, suicidality, mania, alcohol, nicotine and substance dependence (separating heroin and opioids) were assessed using the MAGIC (Todd et al., 2003, PMID: 14627881), a broad semi-structured psychiatric assessment tool with good reliability and prospective stability. The onset of (any) illicit drug use in this sample is not particularly remarkable (age~16), but the age of onset of heroin use is much lower than in the USA: 25% by age 16; 50% by age 19, with no differences between ethnicities or gender. This is consistent with findings from other studies in Bulgaria. In contrast, in 2008, SAMHSA estimated an average age of 23.4 for new heroin initiates in the USA. Further, progression from first use to regular use appears to be more rapid, with the majority of participants reporting onset of dependence problems within one year of initiation. Another unique aspect of this study population are the comparatively low levels of polysubstance use (outside of nicotine and alcohol). This early-use, fast-transition and monosubstance heroin pattern stands in sharp contrast to what is reported in many studies in the Western World. In our study, 47% of Ethnic Bulgarians and 66% of Roma used only opioids, even years after the onset of drug use. 15.4% of Ethnic Bulgarians and 66.2% of Roma reported heroin as the very first illicit drug used. Lifetime, 12.5% of Ethnic Bulgarians and 52.8% of Roma report never having used another illicit drug other than heroin more than five times. While both Roma and Ethnic Bulgarians certainly experiment with other drugs, abuse/dependence rates for these drugs are low in Ethnic Bulgarians (from 8.4% for inhalants to 28% for stimulants) and in the Roma population (from 1.3% for hallucinogens to 11.2% for stimulants).

  Study phs001804