Emma E. Davenport
A5033170243- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Metabolomics and Mass Spectrometry Studies
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Genetic Associations and Epidemiology
- COVID-19 Clinical Research Studies
- Gut microbiota and health
- Single-cell and spatial transcriptomics
- Pneumonia and Respiratory Infections
- vaccines and immunoinformatics approaches
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Immunodeficiency and Autoimmune Disorders
- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Atherosclerosis and Cardiovascular Diseases
- Adrenal Hormones and Disorders
- Long-Term Effects of COVID-19
- Genomics and Rare Diseases
- interferon and immune responses
- Burkholderia infections and melioidosis
- Adipokines, Inflammation, and Metabolic Diseases
Wellcome Sanger Institute
2020-2025
Centre for Human Genetics
2011-2024
University of Oxford
2011-2024
European Bioinformatics Institute
2023
Brigham and Women's Hospital
2016-2020
Harvard University
2016-2020
Center for Systems Biology
2018-2019
Broad Institute
2016-2019
Mass General Brigham
2016-2017
NOAA National Ocean Service
2013
BackgroundEffective targeted therapy for sepsis requires an understanding of the heterogeneity in individual host response to infection. We investigated this by defining interindividual variation transcriptome patients with and related outcome genetic diversity.MethodsWe assayed peripheral blood leucocyte global gene expression a prospective discovery cohort 265 adult admitted UK intensive care units due community-acquired pneumonia evidence organ dysfunction. then validated our findings...
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire,...
Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores available assays such as blood lactate reflect global illness with suboptimal performance, do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset patients....
Heterogeneity in the septic response has hindered efforts to understand pathophysiology and develop targeted therapies. Source of infection, with different causative organisms temporal changes, might influence this heterogeneity.To investigate individual variations transcriptomic sepsis due fecal peritonitis, compare these same parameters community-acquired pneumonia.We performed genome-wide gene expression profiling peripheral blood leukocytes adult patients admitted intensive care...
Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed neutrophils emergency granulopoiesis drove a maladaptive during sepsis. We generated whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune identified populations immunosuppressive mature immature neutrophils. In co-culture, CD66b+ inhibited proliferation activation CD4+ T...
Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim this study was identify genetic variants survival.
Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs highly variable and a genetic causes have been identified in < 5% patients. Here, we performed whole genome sequencing (WGS) 34 CVID patients (94% sporadic) combined them with transcriptomic profiling (RNA-sequencing B cells) from three healthy controls. We variants disease genes TNFRSF13B, TNFRSF13C, LRBA NLRP12 enrichment known novel pathways. The pathways include B-cell...
Dysregulated host responses to infection can lead organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication biomarkers response are urgently needed. We investigated the use whole-blood transcriptomics for stratification patients with severe by integrating data from 3149 samples sepsis due community-acquired pneumonia or fecal peritonitis admitted intensive care healthy individuals into a gene expression reference map. used...
Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry delineate plasma proteome for sepsis comparator groups (noninfected critical illness, postoperative inflammation, healthy volunteers) involving 2612 samples (from 1611 patients) 4553 liquid chromatography–mass analyses acquired...
Despite significant progress in annotating the genome with experimental methods, much of regulatory noncoding remains poorly defined. Here we assert that elements may be characterized by leveraging local epigenomic signatures where specific transcription factors (TFs) are bound. To link these two features, introduce IMPACT, a annotation strategy identifies defined cell-state-specific TF binding profiles, learned from 515 chromatin and sequence annotations. We validate IMPACT using multiple...
Abstract Although alterations in myeloid cells have been observed COVID-19, the specific underlying mechanisms are not completely understood. Here, we examine function of classical CD14 + monocytes patients with mild and moderate COVID-19 during acute phase infection healthy individuals. Monocytes from display altered expression cell surface receptors a dysfunctional metabolic profile that distinguish them monocytes. Secondary pathogen sensing ex vivo leads to defects pro-inflammatory...
Rationale Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery targeting immunomodulatory therapies. Clustering approaches using clinical circulating biomarkers have defined hyper-inflammatory hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar exist sepsis populations where leucocyte transcriptomic-defined been reported. Objectives We...
Cytokines are critical to human disease and attractive therapeutic targets given their widespread influence on gene regulation transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central defining drug mechanisms. One promising strategy use interactions between expression quantitative trait loci (eQTLs) cytokine levels define target genes
Despite increases in vaccination coverage, reductions influenza-related mortality have not been observed. Better vaccines are therefore required and influenza challenge studies can be used to test the efficacy of new vaccines. However, this requires accurate post-challenge classification subjects by outcome, which is limited current methods that use artificial thresholds assign 'symptomatic' 'asymptomatic' phenotypes. We present data from an study 22 healthy adults (11 vaccinated) were...
Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage genome-scale metabolic networks define affect biochemical reaction fluxes across tissues, including skeletal muscle, adipose, liver, brain heart. As proof concept, build personalised organ-specific flux models for 524,615 individuals INTERVAL UK Biobank cohorts perform fluxome-wide association...
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin nails. It can be acquired or caused primary immune deficiencies, particularly those that impair interleukin (IL)-17 IL-22 immunity. We describe a single kindred CMC identification of STAT1 GOF mutation whole exome sequencing (WES). show how detailed clinical immunological phenotyping this family in context WES has enabled...
Abstract Epstein-Barr virus (EBV) reactivation is common in sepsis patients but the extent and nature of this remains unresolved. We sought to determine incidence correlates EBV-positivity a large cohort. also hypothesised that EBV would be increased whom relative immunosuppression was major feature their response. To identify such we aimed use knowledge response subphenotypes based on transcriptomic studies circulating leukocytes, specifically with Sepsis Response Signature endotype (SRS1)...
To identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE).For the study, 673 patients with SLE (diagnosed according American College Rheumatology 1997 updated classification criteria) were matched by age, sex, race (first 3 principal components) 3,272 control subjects without a history connective tissue disease. Smoking status was classified as smoking/having recently quit within 4 years before...
Gene misexpression is the aberrant transcription of a gene in context where it usually inactive. Despite its known pathological consequences specific rare diseases, we have limited understanding wider prevalence and mechanisms humans. To address this, analyzed 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors. We found that while individual events occur rarely, aggregate they were almost all third inactive protein-coding genes. Using 2,821 paired whole-genome...
Abstract Aims The apelin receptor, a G protein-coupled has emerged as key regulator of cardiovascular development, physiology, and disease. However, there is lack suitable human in vitro models to investigate the apelinergic system cell types. For first time we have used embryonic stem cell-derived cardiomyocytes (hESC-CMs) novel inducible knockdown examine role receptor both cardiomyocyte development determine consequences loss function model Methods results Expression its ligands hESCs...