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• Immune signature of malignant melanoma in pregnancy

  Melanoma is a highly immunogenic malignancy and there is a deep-rooted notion among clinicians that a probable systemic immunosuppressed state during pregnancy would negatively influence melanoma related prognosis. To test this hypothesis on a more fundamental level, we collected a unique set of melanoma tumor samples and performed RNAseq to draw comparisons between the immune cell infiltrate of pregnant patients and non-pregnant matched controls. We found that there is indeed no differential expression of any immune cell subset. This underscores the notion that the supposed immunosuppressive state of pregnancy does not hamper the anti-tumor immune response.

  Study EGAS50000000492

• Age related Macular Degeneration (AMD)-- Michigan, Mayo, AREDS, Pennsylvania (MMAP) Cohort Study: A Joint Genome Wide Association Study

  Age-related Macular Degeneration (AMD) is a leading cause of incurable blindness in people over the age of 65. AMD is a late-onset multi-factorial neurodegenerative disease and its pathogenesis involves interaction of genetic and environmental factors. Several chromosomal regions have been associated with AMD susceptibility through linkage analysis (Swaroop et al., 2009). More recent studies provide strong evidence that variants within the CFH gene cluster on chromosome 1 and at/near LOC387715/ARMS2 on chromosome 10 are strongly associated with disease. Variants at other genes including C2/BF, C3, CFI and APOE4, also contribute to AMD susceptibility. Our primary goals are to identify genetic variants and haplotypes that are associated with AMD. The underlying hypothesis is that DNA variation(s) in multiple genetic susceptibility loci will predispose individuals to AMD pathogenesis, and comparison of DNA of cases and controls should identify these susceptibility variants. Our studies are focused on the genetic analysis of advanced AMD and should provide novel insights into disease diagnosis, progression and pathology. We have assembled a collaborative group of researchers from the University of Michigan, Mayo Clinic, University of Pennsylvania, and the AREDS group including National Eye Institute intramural investigators, who collected clinical data and DNA from a large number of patients affected with AMD and from unaffected controls. The primary source of funding was National Eye Institute. Through this collaborative effort, we submitted and obtained usable genotyping data on 2184 patients and 1155 controls from the Center for Inherited Disease Research (CIDR).

  Study phs000182

• Comprehensive genomic analysis of colorectal cancer with microsatellite instability

  Microsatellite instability-high (MSI-H) colorectal cancers (CRCs) account for 10?15% of all CRCs. MSI-H CRC is characterized by a large number of somatic insertions/deletions (indels) resulting from either mutations within or the silencing of genes involved in the DNA mismatch repair (MMR) system. A subset of MSI-H CRCs is associated with Lynch syndrome (LS), which is caused by germline MMR gene mutations, leading to hereditary cancer predisposition. Other than frequent somatic mutations in BRAF, the transformation mechanisms underlying MSI-H CRC are largely unknown. Here, genomic DNA from 149 MSI-H CRC specimens was analyzed using whole-exome sequencing, and 93 of these samples were subjected to genome-wide DNA methylation analysis. Furthermore, transcriptome sequencing was conducted on 111 samples. Genomic/epigenomic analyses identified three subgroups within our cohort: (1) MSI-H CRCs with silenced MLH1 that share frequent indels, a specific mutation/copy number alteration profile and promoter DNA methylation; (2) LS-associated MSI-H CRCs with MMR genes containing germline mutations; and (3) the remaining MSI-H CRCs with frequent somatic disruptive mutations of MLH1 or MSH2. Unexpectedly, only the first group was found to frequently carry fusion-type protein kinases (15% of this group and 9.9% of all MSI-H CRCs) that are promising therapeutic targets. Thus, MSI-H CRCs can be classified into three subgroups with distinctive genomic as well as epigenomic statuses, probably reflecting the oncogenic processes of these cancers. Fusion-type kinases are enriched in MSI-H CRCs, shedding new light on potential treatment strategies.

  Study JGAS000113

• Deep Sequencing Studies for Cannabis and Stimulant Dependence

  Cannabis and stimulants are among the most widely used illicit drug in the United States, and their use is associated with substantial physical and psychiatric sequelae. Twin studies have shown a substantial genetic component to the etiology of cannabis and stimulant use disorders, but, genome-wide association studies using genotype data obtained from microarrays have yielded few robust results. The advent of increasingly economical whole genome sequencing provides new opportunities to identify trait-associated sequence variations. The present study proposes to identify sequence variants that affect stimulant and cannabis dependence in three cohorts. The three study cohorts were ascertained as part of the Mission Indian Study (PI Cindy Ehlers), the combined Yale-University of Connecticut Addiction Study samples (PI Joel Gelernter) and the San Francisco Family Study (PI Kirk Wilhelmsen). Because three populations with different continental origins were studied, the present study will also ascertain whether the major genetic risk factors for the traits of interest are shared or population-specific.

  Study phs001458

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: Team SAE

  The goal of this project is to develop a smartphone-based platform to monitor and support individuals with COVID-19 symptoms (who may need testing) and those who have already tested positive. The app will integrate a Bluetooth-enabled thermometer and pulse oximeter into an approach uniquely designed for low-resource settings and underserved populations. This project will focus on the American Indian/Alaskan Native (AI/AN) underserved population and will determine the feasibility of the digital health solution to collect symptom survey data and vital data including temperature, pulse, and oxygen saturation level. The complete study will include 300 participants 100% medically underserved with at least 51% from the AI/AN community. A combination of hard and soft data will be collected consisting of vital data, medical history and questionnaire data, and participant COVID-19 viral and antibody testing results collected during the study.DOI: https://rapids.ll.mit.edu/10.57895/wv88-by98

  Study phs002534

• Single-cell RNA-Seq analysis of thymic ILC1 progenitors and NK cell differentiation This analysis involved a multiplexed sequencing run to study thymic innate lymphoid cells (ILCs) and NK progenitors. The generated data requires a demultiplexing file to separate and identify the individual sample tags for downstream analysis.

  This dataset contains multiplexed single-cell RNA sequencing (scRNA-seq) data from human thymic tissue, focusing on ILC1 progenitors and NK cell differentiation. The data were generated using the BD Rhapsody system and sequenced on the Illumina NovaSeq S4 platform. A demultiplexing file is required to assign sample identities.

  Dataset EGAD50000001157

• Congenital anosmia 1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002210

• NHGRI Genome Integrity of iPSCs Study

  The purpose of this study is to compare mutation load in induced pluripotent stem cells derived from skin fibroblasts.

  Study phs001277

• Single Cell Targeted Sequence Capture

  This study is to ascertain whether it is feasible to extract single cell from a tumour, perform amplification, generate a library and sequence a targeted pulldown.

  Dataset EGAD00001001450

• Bruno et al.: Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring

  Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production. Here, we show that myeloid innate immune cells of CGD patients are transcriptionally and functionally reprogrammed to a hyperactive inflammatory status, displaying an impaired in vitro induction of trained immunity. CGD monocytes have reduced intracellular amino acids concentrations and profound functional metabolic defects, both at the level of glycolysis and mitochondrial respiration. Ex vivo and in vivo treatment with IFN-γ restored these metabolic defects and reduced excessive IL-1β and IL-6 production in response to fungal stimuli in CGD monocytes. These data suggest that prophylactic rIFNγ modulates the metabolic status of innate immune cells in CGD. These data shed light on the effects of NADPH-derived ROS deficiency to the metabolic programs of immune cells and pose the basis for targeting this immunometabolic axis, potentially beyond CGD, with IFN-γ immunotherapy.

  Study EGAS00001005463