Davenport Group | Functional Genomics

Davenport Group | Functional Genomics

Davenport Group

patienthetexpexperiments.jpg

Our Research and Approach

We combine genomic analysis with clinical data to understand how genetics contributes to the variation between patients in their disease severity and response to treatments.

Through clinical and industry collaborations, we analyse gene expression datasets from cohorts of patients with diseases that involve systemic inflammation such as sepsis and autoimmune diseases. The main aim is to identify gene expression signatures for predicting disease severity and treatment response as well as using expression quantitative trait locus (eQTL) mapping to understand the role of regulatory DNA in patient heterogeneity.

Patient stratification from transcriptomic profiling

Sepsis is a life-threatening condition that occurs when the body's immune system damages it's own tissues and organs while trying to fight an infection. There is great individual variation in the way that people respond making sepsis a challenging disease to diagnose and treat. The underlying infection can be treated with antibiotics and failing organs can be supported but we still don't have treatments that tackle the immune response that is damaging the organs. We use transcriptomic profiling to stratify patients and further our understanding of the individual response to sepsis. We are exploring the transcriptomic response in patients presenting to the emergency room with suspected infection (BioAID) and in patients with sepsis admitted to the ICU (GAinS).

Role of regulatory DNA variants in patient heterogeneity

We integrate genetic information with our transcriptomic profiles to understand the role of genetics in the variation that we observe. We map expression quantitative trait locus (eQTL) in cohorts of patients and use eQTL interactions to understand how the environment can modulate these regulatory effects. We are interested in interactions both with disease severity and treatment with a drug.

Drug target prioritisation from single-cell eQTL mapping

SLE is an autoimmune disease that can affect virtually any organ system in the body. This clinical heterogeneity has made the development of new drugs for treatment very challenging. To enable the development of new therapies, we are interested in better understanding the molecular mechanisms contributing to the disease pathophysiology. In collaboration with Open Targets, we are generating single-cell RNA-sequencing for a cohort of SLE patients. This will allow us to map eQTL at the single-cell level and gain mechanistic insights that can inform novel target identification for future drugs.

People

Davenport, Emma
Dr Emma Davenport
Group Leader

Emma Davenport's research focuses on integrating functional genomics and clinical data in order to understand how genetics contributes to the patient-to-patient heterogeneity in treatment response.

Research Programmes and Faciltites

Partners and Funders

Internal Partners
External Partners and Funders

Publications

  • Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial.

    Davenport EE, Amariuta T, Gutierrez-Arcelus M, Slowikowski K, Westra HJ et al.

    Genome biology 2018;19;1;168

  • Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia.

    Burnham KL, Davenport EE, Radhakrishnan J, Humburg P, Gordon AC et al.

    American journal of respiratory and critical care medicine 2017;196;3;328-339

  • Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study.

    Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P et al.

    The Lancet. Respiratory medicine 2016;4;4;259-71

  • Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

    van Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B et al.

    Clinical immunology (Orlando, Fla.) 2015;160;2;301-14

  • Transcriptomic profiling facilitates classification of response to influenza challenge.

    Davenport EE, Antrobus RD, Lillie PJ, Gilbert S and Knight JC

    Journal of molecular medicine (Berlin, Germany) 2015;93;1;105-14

  • IMPACT: Genomic Annotation of Cell-State-Specific Regulatory Elements Inferred from the Epigenome of Bound Transcription Factors.

    Amariuta T, Luo Y, Gazal S, Davenport EE, van de Geijn B et al.

    American journal of human genetics 2019;104;5;879-895

  • Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial.

    Davenport EE, Amariuta T, Gutierrez-Arcelus M, Slowikowski K, Westra HJ et al.

    Genome biology 2018;19;1;168

  • A community approach to mortality prediction in sepsis via gene expression analysis.

    Sweeney TE, Perumal TM, Henao R, Nichols M, Howrylak JA et al.

    Nature communications 2018;9;1;694

  • Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study.

    Scicluna BP, van Vught LA, Zwinderman AH, Wiewel MA, Davenport EE et al.

    The Lancet. Respiratory medicine 2017;5;10;816-826

  • Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia.

    Burnham KL, Davenport EE, Radhakrishnan J, Humburg P, Gordon AC et al.

    American journal of respiratory and critical care medicine 2017;196;3;328-339

  • Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility.

    Dhalla F, Fox H, Davenport EE, Sadler R, Anzilotti C et al.

    Clinical and experimental immunology 2016;184;2;216-27

  • Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study.

    Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P et al.

    The Lancet. Respiratory medicine 2016;4;4;259-71

  • Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

    van Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B et al.

    Clinical immunology (Orlando, Fla.) 2015;160;2;301-14

  • Factors influencing success of clinical genome sequencing across a broad spectrum of disorders.

    Taylor JC, Martin HC, Lise S, Broxholme J, Cazier JB et al.

    Nature genetics 2015;47;7;717-726

  • Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study.

    Rautanen A, Mills TC, Gordon AC, Hutton P, Steffens M et al.

    The Lancet. Respiratory medicine 2015;3;1;53-60

  • Transcriptomic profiling facilitates classification of response to influenza challenge.

    Davenport EE, Antrobus RD, Lillie PJ, Gilbert S and Knight JC

    Journal of molecular medicine (Berlin, Germany) 2015;93;1;105-14

  • A common haplotype of the TNF receptor 2 gene modulates endotoxin tolerance.

    Fairfax BP, Davenport EE, Makino S, Hill AV, Vannberg FO and Knight JC

    Journal of immunology (Baltimore, Md. : 1950) 2011;186;5;3058-65