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• Genome-Wide Characterization of Pancreatic Adenocarcinoma Patients Using Next Generation Sequencing

  In this study, we whole genome sequenced tumor/normal pairs from three pancreatic adenocarcinoma patients to separately characterize each patient with respect to somatic alterations. For 2 patients for whom tumor RNA was available, we also performed RNA sequencing to evaluate gene expression changes. While additional sequencing is needed to improve our understanding of the disease, the information acquired from this study contributes to our knowledge base on pancreatic cancer and helps to establish a foundation for identifying and developing more efficacious treatments for patients.

  Study phs000550

• Prediction of DNA Repair Inhibitor Response in Short Term Patient-Derived Ovarian Cancer Organoids

  In this study, 34 ovarian tumor organoids generated from 23 patients underwent paired DNA damage repair defect functional analyses and whole exome sequencing analysis to compare genetic mutational status to DNA repair functional capacity. 22 of the patients had high grade serous cancer and 1 of the patients had low grade serous cancer. A normal control, fresh parent tumor, and cells from the organoid culture generated from the parent tumor underwent whole exome sequencing analysis and the data from the sequencing analysis is provided here.

  Study phs001685

• In Vivo Cytokine eQTL Interactions from a Lupus Clinical Trial

  The purpose of this study is to discover in vivo cytokine expression quantitative trait locus (eQTL) interactions from a cohort of patients with systemic lupus erythematosus. 157 lupus patients were enrolled in a clinical trial to test the efficacy and safety of an anti-IL-6 monoclonal antibody. At three time points, we measured interferon (IFN) status, anti-IL-6 drug exposure and genome-wide gen expression. We identified 4,818 cis-eQTLs and then observed a statistically significant enrichment of in vivo eQTL interactions with IFN status and anti-IL-6 exposure.

  Study phs001702

• Germline Genome Sequencing from Patients with Early-Onset Merkel Cell Carcinoma

  Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer associated with advanced age. Approximately 5% of cases are early-onset MCC, occurring in individuals younger than 50 years. This study used genome sequencing to identify germline risk factors among patients with early-onset MCC. The available data in the database of Genotypes and Phenotypes (dbGaP) includes genome sequencing of peripheral blood mononuclear cell (PBMC) DNA from 37 patients with early-onset MCC (age ATM = 2, BRCA1 = 2, BRCA2 = 1, TP53 = 1, and MAGT1 = 1).

  Study phs003485

• Protracted Neuronal Recruitment in the Temporal Lobe of Young Children

  This study describes a stream of migrating neurons directed to the human entorhinal cortex. This migration is among the most protracted in the developing human brain, with young neurons still arriving at 2-3 years of age. We did not observe a similar migratory process in the early postnatal macaque brain, which suggests that this migration may be uniquely delayed or extended into early postnatal human life. Using immunohistochemistry and single‐cell RNA sequencing (scRNA‐seq), we identified these late-arriving neurons as being mainly CGE-derived LAMP5+/RELN+ interneurons.

  Study phs003509

• Resistance to Latent Mycobacterium tuberculosis Infection in Uganda: Immunologic Profiling

  Despite significant exposure to Mycobacterium tuberculosis (Mtb), some humans remain uninfected, as defined by persistently negative immune sensitization tests (tuberculin skin test, TST; interferon gamma release assays, IGRA). To explore mechanisms of natural resistance to Mtb infection, we profiled tissues from highly-exposed Mtb contacts from Uganda. The cohort from this submission were household contacts of pulmonary tuberculosis cases who were followed longitudinally over 8 years and maintained negative TST and IGRA testing on serial evaluations. This cohort is well-described (Stein et al. 2019, PMID: 30165605).

  Study phs002445

• Multivalent State Transitions Shape the Intratumoral Composition of Small Cell Lung Carcinoma

  Small cell lung carcinoma (SCLC) is an aggressive, tobacco-associated tumor characterized by rapid growth, early metastases, and initial response followed by almost invariable resistance to chemotherapy. Studies to date have not resolved the extent that diverse transcriptional programs drive SCLC and contribute to its lethality. We combined patient-derived xenograft (PDX) (n = 64) resources with multi-omic profiling, single-cell fluorescence tracking of ex vivo tumor cells, and mathematical and statistical models to study the topology of the SCLC transcriptional state space and its plasticity.

  Study phs003102

• Single-Cell Analysis of the Multiple Myeloma Microenvironment after Gamma-Secretase Inhibition and CAR T-Cell Therapy

  We examined the effects of gamma-secretase inhibition (GSI) on the bone marrow microenvironment in multiple myeloma patients before anti-B-cell maturation antigen (BCMA) CAR T-cell therapy. Single-nuclei RNA and ATAC sequencing revealed significant changes in gene expression and chromatin accessibility, especially in monocytes and tumor cells, following exposure to GSI. The findings suggest that GSI influences not only BCMA signaling but also broader cellular interactions within the tumor microenvironment. De-identified sequencing data from the study is available through dbGaP.

  Study phs003741

• PARK7/DJ-1 deficiency modulates microglial activation in response to LPS-induced inflammation

  Specific microglia responses are thought to contribute to the development and progression of various neurodegenerative diseases, including Parkinson’s disease (PD). However, the phenotypic acquisition of microglial cells and their role during the underlying neuroinflammatory processes remain largely obscure. Here, according to the multiple-hit hypothesis, which stipulates that PD etiology is determined by a combination of genetics and various environmental risk factors, we investigate microglial transcriptional programs and morphological adaptations under PARK7/DJ-1 deficiency, a genetic cause of PD, during lipopolysaccharide (LPS)-induced inflammation.

  Study EGAS50000000202

• NHLBI TOPMed: Women's Health Initiative (WHI)

  This is Whole Genome Sequencing data from the TOPMed participation of the Women's Health Initiative. Approximately 11,100 subjects were involved in this study: approximately 1,100 cases of VTE, 4,000 cases of ischemic stroke, 900 cases of hemorrhagic stroke, and 5,100 controls. Summary level phenotypes for the WHI Cohort study participants can be viewed at the top-level study page phs000200 WHI Cohort. Individual level phenotype data and molecular data for all WHI top-level study and substudies are available by requesting Authorized Access to the WHI Cohort study phs000200.

  Study phs001237