Scholars@Duke
Thomas Burke

Thomas Burke

Manager, Systems Project
The Precision Medicine Program
Duke Box 3382, Durham, NC 27710
101 Science Drive, CIEMAS Bldg. Rm. 2177B, Durham, NC 27708

Selected Publications

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.

Journal Article Nat Commun · March 10, 2025 Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized ... Full text Open Access Link to item Cite

A Rapid Host Response Blood Test for Bacterial/Viral Infection Discrimination Using a Portable Molecular Diagnostic Platform.

Journal Article Open Forum Infect Dis · January 2025 BACKGROUND: Difficulty discriminating bacterial versus viral etiologies of infection drives unwarranted antibacterial prescriptions and, therefore, antibacterial resistance. METHODS: Utilizing a rapid portable test that measures peripheral blood host gene ... Full text Link to item Cite

Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Journal Article Open Forum Infect Dis · March 2024 BACKGROUND: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implement ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Open Access Link to item Cite

Integrated epigenomic exposure signature discovery.

Journal Article Epigenomics · 2024 Aim: The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis.Materials & methods: Here we developed and implemented a machine learning algorithm, the exposure ... Full text Link to item Cite

Dynamics of cytokine and antibody responses in community versus hospital SARS-CoV-2 infections.

Journal Article Front Immunol · 2024 INTRODUCTION: Dysregulated host cytokine responses to SARS-CoV-2 infection are a primary cause of progression to severe disease, whereas early neutralizing antibody responses are considered protective. However, there are gaps in understanding the early tem ... Full text Link to item Cite

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Journal Article Sci Rep · December 18, 2023 Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant ... Full text Link to item Cite

Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.

Journal Article J Clin Invest · October 2, 2023 Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where the ... Full text Link to item Cite

COVID-19 Diagnosis and SARS-CoV-2 Strain Identification by a Rapid, Multiplexed, Point-of-Care Antibody Microarray.

Journal Article Anal Chem · April 4, 2023 Antigen tests to detect SARS-CoV-2 have emerged as a promising rapid diagnostic method for COVID-19, but they are unable to differentiate between variants of concern (VOCs). Here, we report a rapid point-of-care test (POC-T), termed CoVariant-SPOT, that us ... Full text Open Access Link to item Cite

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Journal Article Cell Rep Methods · February 27, 2023 Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stabi ... Full text Open Access Link to item Cite

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Journal Article PLoS One · 2023 Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to d ... Full text Link to item Cite

Pre-exposure cognitive performance variability is associated with severity of respiratory infection.

Journal Article Sci Rep · December 30, 2022 Using data from a longitudinal viral challenge study, we find that the post-exposure viral shedding and symptom severity are associated with a novel measure of pre-exposure cognitive performance variability (CPV), defined before viral exposure occurs. Each ... Full text Link to item Cite

Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature.

Journal Article Cell Syst · December 21, 2022 The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we ... Full text Link to item Cite

Host Gene Expression to Predict Sepsis Progression.

Journal Article Crit Care Med · December 1, 2022 OBJECTIVES: Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection pre ... Full text Link to item Cite

Single-cell genome-wide association reveals that a nonsynonymous variant in ERAP1 confers increased susceptibility to influenza virus.

Journal Article Cell Genom · November 9, 2022 During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human in vitro susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and ... Full text Link to item Cite

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

Journal Article Sci Rep · July 9, 2022 SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG ... Full text Open Access Link to item Cite

SARS-CoV-2 reinfection across a spectrum of immunological states.

Journal Article Health Sci Rep · July 2022 PURPOSE: Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved unders ... Full text Open Access Link to item Cite

Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes.

Journal Article Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · May 2022 BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with coronavirus disease 2019 (COVID-19), but it is not clear whether this RNAemia reflects viremia (ie, virus ... Full text Open Access Cite

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Journal Article JAMA Netw Open · April 1, 2022 IMPORTANCE: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacter ... Full text Open Access Link to item Cite

Rapid test to assess the escape of SARS-CoV-2 variants of concern.

Journal Article Sci Adv · December 3, 2021 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are concerning in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a rapid test, termed CoVariant-SCAN, that detects neutralizing antibodies (nAbs) capable of ... Full text Link to item Cite

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.

Journal Article Crit Care Med · October 1, 2021 OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response b ... Full text Open Access Link to item Cite

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

Journal Article JCI Insight · September 8, 2021 As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or m ... Full text Link to item Cite

Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.

Journal Article JAMA Netw Open · September 1, 2021 IMPORTANCE: Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation. OBJECTIVE: To evaluate the feasibility of usin ... Full text Open Access Link to item Cite

Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.

Journal Article Clin Infect Dis · August 16, 2021 BACKGROUND: Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host-response tests remains unknown. We evaluated a host-respons ... Full text Open Access Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · June 11, 2021 BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ... Full text Open Access Link to item Cite

Multiplexed, quantitative serological profiling of COVID-19 from blood by a point-of-care test.

Journal Article Sci Adv · June 2021 Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage coronavirus disease 2019 (COVID-19). Here, we report on a microfluidic POC test that can profile the antibody response against multiple severe acute resp ... Full text Link to item Cite

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.

Journal Article Genome Med · May 17, 2021 BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challeng ... Full text Open Access Link to item Cite

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

Journal Article medRxiv · April 20, 2021 As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or m ... Full text Link to item Cite

A blood-based host gene expression assay for early detection of respiratory viral infection: an index-cluster prospective cohort study.

Journal Article Lancet Infect Dis · March 2021 BACKGROUND: Early and accurate identification of individuals with viral infections is crucial for clinical management and public health interventions. We aimed to assess the ability of transcriptomic biomarkers to identify naturally acquired respiratory vi ... Full text Open Access Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat Commun · February 17, 2021 SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ... Full text Open Access Link to item Cite

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.

Journal Article Front Immunol · 2021 Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the sha ... Full text Open Access Link to item Cite

A comparison of host response strategies to distinguish bacterial and viral infection.

Journal Article PLoS One · 2021 OBJECTIVES: Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). METHODS: In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expressi ... Full text Open Access Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches.

Journal Article medRxiv · July 26, 2020 In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial ... Full text Open Access Link to item Cite

Previously Derived Host Gene Expression Classifiers Identify Bacterial and Viral Etiologies of Acute Febrile Respiratory Illness in a South Asian Population.

Journal Article Open Forum Infect Dis · June 2020 BACKGROUND: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI i ... Full text Open Access Link to item Cite

Nasal microbiota exhibit neither reproducible nor orderly dynamics following rhinoviral infection

Journal Article · April 17, 2020 ABSTRACTBackgroundHow human-associated microbial communities resist and respond to perturbations remains incompletely understood. Viral challenge provides one opportunity to test how human ... Full text Cite

Rapid, Sample-to-Answer Host Gene Expression Test to Diagnose Viral Infection.

Journal Article Open Forum Infect Dis · November 2019 OBJECTIVE: Distinguishing bacterial, viral, or other etiologies of acute illness is diagnostically challenging with significant implications for appropriate antimicrobial use. Host gene expression offers a promising approach, although no clinically useful ... Full text Open Access Link to item Cite

Direct-from-blood RNA sequencing identifies the cause of post-bronchoscopy fever.

Journal Article BMC Infect Dis · October 28, 2019 BACKGROUND: Antibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and freque ... Full text Open Access Link to item Cite

Validation of a host response test to distinguish bacterial and viral respiratory infection.

Journal Article EBioMedicine · October 2019 Featured Publication BACKGROUND: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we v ... Full text Open Access Link to item Cite

A host gene expression approach for identifying triggers of asthma exacerbations.

Journal Article PLoS One · 2019 RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable ... Full text Open Access Link to item Cite

A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.

Journal Article Front Microbiol · 2018 Background: Acute respiratory infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to th ... Full text Open Access Link to item Cite

Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

Journal Article EBioMedicine · March 2017 Featured Publication Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with infl ... Full text Open Access Link to item Cite

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

Journal Article J Infect Dis · May 1, 2016 Featured Publication BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene ex ... Full text Open Access Link to item Cite

An individualized predictor of health and disease using paired reference and target samples.

Journal Article BMC Bioinformatics · January 22, 2016 BACKGROUND: Consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, call ... Full text Link to item Cite

Host gene expression classifiers diagnose acute respiratory illness etiology.

Journal Article Sci Transl Med · January 20, 2016 Featured Publication Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers of ... Full text Open Access Link to item Cite

A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses.

Journal Article Open Forum Infect Dis · January 2016 Featured Publication Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid reso ... Full text Open Access Link to item Cite

Multiplex DNA biosensor for viral infection diagnosis using SERS molecular sentinel-on-chip

Conference Ifmbe Proceedings · January 1, 2015 The development of sensitive and selective techniques for multiplex detection of DNA biomarkers is paramount for clinical diagnosis. Various multiplex DNA detection techniques have been reported. However, most of these techniques require multiple incubatio ... Full text Cite

The current epidemiology and clinical decisions surrounding acute respiratory infections.

Journal Article Trends Mol Med · October 2014 Acute respiratory infection (ARI) is a common diagnosis in outpatient and emergent care settings. Currently available diagnostics are limited, creating uncertainty in the use of antibacterial, antiviral, or supportive care. Up to 72% of ambulatory care pat ... Full text Link to item Cite

Comparing reference-based RNA-Seq mapping methods for non-human primate data.

Journal Article BMC Genomics · July 7, 2014 BACKGROUND: The application of next-generation sequencing technology to gene expression quantification analysis, namely, RNA-Sequencing, has transformed the way in which gene expression studies are conducted and analyzed. These advances are of particular i ... Full text Link to item Cite

Multiplex detection of disease biomarkers using SERS molecular sentinel-on-chip.

Journal Article Anal Bioanal Chem · May 2014 Developing techniques for multiplex detection of disease biomarkers is important for clinical diagnosis. In this work, we have demonstrated for the first time the feasibility of multiplex detection of genetic disease biomarkers using the surface-enhanced R ... Full text Link to item Cite

A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

Journal Article Sci Transl Med · September 18, 2013 Featured Publication Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to ... Full text Link to item Cite

Surface-enhanced Raman scattering molecular sentinel nanoprobes for viral infection diagnostics.

Journal Article Anal Chim Acta · July 5, 2013 In this paper, we describe a surface-enhanced Raman scattering (SERS)-based detection approach, referred to as "molecular sentinel" (MS) plasmonic nanoprobes, to detect an RNA target related to viral infection. The MS method is essentially a label-free tec ... Full text Link to item Cite

Human biospecimen research: experimental protocol and quality control tools.

Journal Article Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · April 2009 Full text Cite

Centralized biorepositories for genetic and genomic research.

Journal Article JAMA · March 19, 2008 Featured Publication Full text Link to item Cite

Analysis of Cdc6 function in the assembly of mammalian prereplication complexes.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · February 2002 Eukaryotic DNA replication requires the previous formation of a prereplication complex containing the ATPase Cdc6 and the minichromosome maintenance (Mcm) complex. Although considerable insight has been gained from in vitro studies and yeast genetics, the ... Full text Cite

Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1.

Journal Article The Journal of biological chemistry · May 2001 Featured Publication The minichromosome maintenance (MCM) proteins, together with the origin recognition complex (ORC) proteins and Cdc6, play an essential role in eukaryotic DNA replication through the formation of a pre-replication complex at origins of replication. We used ... Full text Cite

Sp1 activation of a TATA-less promoter requires a species-specific interaction involving transcription factor IID.

Journal Article Nucleic acids research · February 1998 Sp1 is a ubiquitous activator of numerous TATA-containing and TATA-less promoters within the human genome. This transcription factor is distinct from several other mammalian activators because it cannot stimulate transcription of reporter genes when ectopi ... Full text Cite

The DPE, a conserved downstream core promoter element that is functionally analogous to the TATA box.

Conference Cold Spring Harbor symposia on quantitative biology · January 1998 Full text Cite

The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila.

Journal Article Genes & development · November 1997 Featured Publication We analyzed the function of the downstream promoter element (DPE), a distinct 7-nucleotide core promoter element that is approximately 30 nucleotides downstream of the transcription start site of many TATA-box-deficient (TATA-less) promoters in Drosophila. ... Full text Cite

Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters.

Journal Article Genes & development · March 1996 Featured Publication We describe the identification and characterization of a conserved downstream basal promoter element that is present in a subset of Drosophila TATA-box-deficient (TATA-less) promoters by using purified, epitope-tagged TFIID complex (eTFIID) from embryos of ... Full text Cite

Structure of the genes encoding transcription factor IIB and TATA box-binding protein from Drosophila melanogaster.

Journal Article Gene · February 1995 To investigate the structure and regulation of the genes encoding components of the basal RNA polymerase II transcriptional machinery, the Drosophila melanogaster genes encoding transcription factor IIB (TFIIB) and the TATA-box-binding protein (TBP) were i ... Full text Cite

Insulin-like growth factor-I is a serum component stimulating growth of human neuroblastoma.

Journal Article In vitro cellular & developmental biology. Animal · May 1993 Human non-autocrine neuroblastoma cells SK-N-SH and LF require serum for proliferation in vitro. We wished to determine the role of serum-borne insulin-like growth factor I (IGF-I) as mitogen for these cells. Introduction of the monoclonal antibody alpha-I ... Full text Cite

INSULIN-LIKE GROWTH FACTOR-I IS A SERUM COMPONENT STIMULATING GROWTH OF HUMAN NEUROBLASTOMA

Journal Article IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL · May 1, 1993 Link to item Cite