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• Detection of ctDNA in Plasma of Patients with Clinically Localised Prostate Cancer is Associated with Rapid Disease Progression

  Dac EGAC00001001718

• Ampliseq library dataset

  This is the dataset for Ampliseq sequencing

  Dataset EGAD50000000536

• Degradation of Cyclin K/CDK12 is a druggable vulnerability of colorectal cancer (H012)

  Study EGAS00001004517

• Increased trunk fat is associated with altered gene expression in breast tissue of normal weight women

  Study EGAS00001005138

• Navarrabiomed DAC for XPAND project

  This DAC is created for the XPAND project by the Translational Bioinformatics unit.

  Dac EGAC50000000462

• DAC Fondazione Michelangelo

  This is the DAC responsible for granting access to sequencing data generated by Fondazione Michelangelo

  Dac EGAC50000000179

• Enrichment of Lung Microbiome with Supraglottic Taxa which is Associated with Increased Pulmonary Inflammation

  Background: The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that micro-aspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. Methods: We sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (9 never-smokers, 14 former-smokers and 6 current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes and neutrophils. Results: BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT. Smoking had no effect on pneumotype allocation, alpha or beta diversity. PneumotypeSCT was associated with higher BAL lymphocyte-count (p = 0.007), BAL neutrophil-count (p = 0.034) and eNO (p = 0.022). Conclusion: A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation.

  Study phs000633

• Oxidative phosphorylation is a key ontogenetic feature of monocyte immunometabolism promoting myeloid differentiation after birth

  Neonates primarily rely on innate immunity, yet their inflammatory responses to microbes, particularly those of monocytes, are usually restricted compared to adults. This is controversially interpreted as immaturity increasing the risk of sepsis or essential programming allowing immune adaptation after birth. Which changes the cellular immunometabolism undergoes after birth and its role in these concepts are poorly defined. Here, we applied transcriptomic, metabolic, and immunological approaches and found that monocytes exhibit an inverse ontogenetic balance of immunometabolism. Our data show that glycolysis in monocytes increases within the first year of life and fuels their inflammatory responsiveness. In contrast, oxidative phosphorylation (OXPHOS) is high in neonatal monocytes supporting myeloid differentiation but declines only gradually during the first five years of life. Treatment of neonatal monocytes with lipopolysaccharide induces an adult-like immunometabolic phenotype. Ketogenic diet restricts glycolysis in adult monocytes, but cannot reactivate OXPHOS and revive a neonatal-like immunometabolic phenotype, suggesting that neonatal metabolism is hardwired and cannot be restored by simple dietary changes. Transcriptional network and population-wide human variation analyses identified E2F1, MYB, STAT1 and FLI1 as important regulators of age-dependent cell functions and related energy demands in human monocytes. Collectively, our findings show that restricted glycolysis and increased OXPHOS are a physiological programming in neonatal monocytes. Premature switching to an adult-like metabolism could untimely enhance inflammatory responses and disrupt important myeloid differentiation, whereas microbial challenges accumulating during childhood seem to induce an essential gradual metabolic switch.

  Study EGAS00001007555

• Exome Sequencing of a family with thrombocytopenia, red cell macrocytosis, and lymphoblastic leukemia predisposition

  A family with a history of bleeding, variable thrombocytopenia, red cell macrocytosis and two cases of pre B-cell acute lymphoblastic leukemia was studied in a single visit. The family was assessed for bleeding history using a bleeding questionnaire. Additionally, complete blood counts were measured and whole blood was collected from five affected individuals and three unaffected individuals for DNA extraction and whole exome sequencing. The goal of this study is to determine the genetic cause of thrombocytopenia, red cell macrocytosis, and predisposition to leukemia in a family. It is hoped that the information obtained from this study will help researchers understand the genetic and molecular basis of platelet and red cell production, as well as leukemia predisposition.

  Study phs000873

• Pharmacogenomics of Metformin Dose Response in T2DM Patients

  Type 2 Diabetes Mellitus (T2DM) is a chronic and sometimes debilitating disease that affects millions of adults in the USA. Metformin is commonly prescribed for T2DM; yet some T2DM patients do not tolerate it or respond well. This pharmacogenomics study will examine response, as both change in T2DM patients' weight and hemoglobin A1c (HbA1c) levels, to different doses of metformin, by extracting this data from the electronic health record (EHR), for T2DM subjects taking metformin found by prescription orders in the EHR, and identified as cases with the EHR phenotype algorithm published by Kho et. al. in 2012 (PMID: 22101970 as part of the eMERGE (electronic Medical Records and Genomics; dbGaP phs000237, phs000297, phs000360, phs000368, phs000888, and phs000948) project.

  Study phs000984