CIDDI BioBank

• SOP-guided sample processing, handling and storage to support clinical genomics research
• Secure, monitored, ultra-low temperature specimen storage with appropriate environmental controls and power redundancy
• Web-based informatics for sample annotation, barcode-based chain of custody tracking, inventory management and data query

Biobanking activities are centralized in the Precision Diagnostics Lab space in CIEMAS building. This central location serves as the sample receipt and accessioning area, provides dedicated sample processing/QC workspace, and offers short-term specimen storage in monitored ultralow freezers. Long term storage is provided in an on campus dedicated freezer room locations and at an off-site Duke facility in Research Triangle Park. Storage facilities are restricted to authorized personnel only and provide appropriate environmental controls. Each freezer unit has 24-hour wireless temperature monitoring, an active-response notification system, and an emergency generator for back-up power. The Biobank utilizes LabVantage™ electronic LIMS to support all aspects of sample management including data entry, barcode-based chain-of-custody tracking and precise inventory location management, specimen annotation, flexible query and data reporting while providing access controls ensuring data security and integrity.

Research Aims

Participants were enrolled in the Duke Emergency Derpartment with suspected infectious illness, with longitudinal samples and data collections. The overall purpose of this study is to identify biomarkers and aid in the development of better diagnostic tools for patients with acute infectious illness.  

Experimental Design

Subjects: 815

Timepoints: variable up to 3

Sample types: 

• plasma:7593
• serum:3119
• PAXgene RNA:2787
• RNA total:195
• nasal lavage:5
• nasal swab:2391
• other whole blood:965
• saliva:1854
• urine:724

Datasets

• Clinical: CRF/clinical data, demographics, EMR 
• Molecular: etiology testing, viral pathogen testing

Publications

• Lydon et al. A Host Gene Expression Approach for Identifying Triggers of Asthma Exacerbations. PLoS One (2019)
• Tsalik et al. Host Gene Expression Classifiers Diagnose Acute Respiratory Illness Etiology. Science Translational Medicine (2016)
• Zaas et al. A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine (2013)

Research Aims

Emergency Department enrollment with suspected infectious illnesses including acute respiratory tract infection (ARI), sepsis, and “sepsis-like illness” (i.e., SIRS), with longitudinal samples and data collections. Supported by ACESO (Austere environments Consortiumfor Enhanced Sepsis Outcomes) and NIH-supported ARLG (Antibacterial Resistance Leadership Group) RADICAL (Rapid Diagnostics in Categorizing Acute Lung Infections) Study.Iincludes acute infection from Duke and other US sites.

Experimental Design

Subjects: 929

Timepoints: variable up to 7

Sample types:

• plasma:8667
• serum:6318
• PAXgene RNA:5913
• RNA total:193
• nasal lavage:1
• nasal swab:4478
• other whole blood:1656
• Lavage, Bronchoalveaolar:4
• saliva:4
• urine:491

Datasets

• Clinical: CRF/clinical data, demographics, microbiology, clinical adjudication
• Molecular: viral pathogen testing, strep antigen, blood RNA microarray, RNAseq RT-PCR, plasma procalictonin, metabolomics, proteomics

Publications

• Liu et al. Average Weighted Accuracy: Pragmatic Analysis for a Rapid Diagnostics in Categorizing Acute Lung Infections (RADICAL) Study. Clinical Infectious Diseases (2020)
• Lydon et al. A Host Gene Expression Approach for Identifying Triggers of Asthma Exacerbations. PLoS One (2019)

Research Aims

RADICAL II (Rapid Diagnostics in Categorizing Acute Lung Infections-II) is a multi-site investigation designed to evaluate the performance of a blood-based host response gene expression signature for its ability to discriminate bacterial, viral or non-infectious etiologies in patients with acute respiratory symptoms. The study prospectively enrolled subjects who present to the emergency department with acute upper respiratory tract symptoms.

Experimental Design

Subjects: 754

Timepoints: 1

Sample types:

• plasma:2626
• serum:1982
• PAXgene RNA:5329
• nasal swab:2958
• other whole blood:490
• urine:697

Datasets

Clinical: CRF/clinical data, demographics, microbiology, clinical adjudication

Molecular: blood RNAseq and RT-PCR, plasma cytokines, plasma procalcitonin, strep antigen 

Publications

• Liu et al. Average Weighted Accuracy: Pragmatic Analysis for a Rapid Diagnostics in Categorizing Acute Lung Infections (RADICAL) Study. Clinical Infectious Diseases (2020)
• Lydon et al. A Host Gene Expression Approach for Identifying Triggers of Asthma Exacerbations. PLoS One (2019)

Research Aims

A biorepository study conducted at UNC-Chapel Hill that enrolled patients presenting to the UNC emergency department with suspected infectious illness.

Experimental Design

Subjects: 617 

Timepoints: variable up to 4

Sample types:

• plasma:6316
• serum:2396
• PAXgene RNA:1757
• nasal lavage:243
• nasal swab:2398
• saliva:1858
• RNA total:92
• urine:748

Datasets

Clinical: CRF/clinical data, demographics, EMR

Molecular: viral pathogen testing

Publications

• Lydon et al. A Host Gene Expression Approach for Identifying Triggers of Asthma Exacerbations. PLoS One (2019)

• Tsalik et al. Host Gene Expression Classifiers Diagnose Acute Respiratory Illness Etiology. Science Translational Medicine (2016)

• Zaas et al. A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine (2013)

Research Aims

Emergency Department infectious illness biospecimen and data collections from multiple sites including Northwestern and UCLA, as well as research participants from Melbourne, AUS who were exposed or vaccinated to influenza (including novel 2009 Pandemic H1N1 influenza). 

Experimental Design

Subjects: 247

Timepoints: 1

Sample type:

• PAXgene RNA:514

Datasets

Clinical: CRF/clinical data, demographics, clinical adjudication

Molecular:  host blood RNA microarray, host blood RNAseq, etiology testing

Publications

• Lydon et al. A Host Gene Expression Approach for Identifying Triggers of Asthma Exacerbations. PLoS One (2019)

• Tsalik et al. Host Gene Expression Classifiers Diagnose Acute Respiratory Illness Etiology. Science Translational Medicine (2016)

• Zaas et al. A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine (2013)

Research Aims

Molecular and Epidemiological Study of Suspected Infection (MESSI) is an observational multi-visit study enrolling patients in outpatient clinic, emergency department or hospital, as well as patients in the community with suspected symptoms of infection (bacterial, viral, parasitic or tick-borne infection, or with symptoms that mimic infectious illness). The primary objective is to identify biomarkers for early diagnosis, or for prognosis of poor outcome. Since March 2020, MESSI includes subjects with confirmed or suspected SARS-CoV-2 (COVID-19) infection or known exposure. 

Experimental Design

Subjects: 466

Timepoints: Variable up to 10

Sample types:

• NPOP:5442
• serum:12050
• PAXgene RNA:2122
• plasma:13655
• PBMC:7159
• whole blood:51
• saliva:472
• urine:29

Datasets

Clinical: CRF/clinical data, demographics, symptom survey, clinical adjudication

Molecular: Blood RNAseq, PBMC bulk and single-cell RNAseq, PBMC bulk and single-cell ATACseq, whole exome seq, pathogen etiology testing, SARS2 qPCR, SARS2 serology and quant immune assays

Publications

• McClain et al. Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches. medRxiv (2020)

Research Aims

Experimental Human Rhinovirus (HRV serotype 39) challenge study in healthy volunteers. The purpose of this study is to determine specific biomarker signatures predictive of an impending respiratory illness before the onset of symptoms. Participants were inoculated with HRV, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed in collaboration with the University of Virginia (2007).

Experimental Design

Subjects: 20

Timepoints: 1

Sample Types: 

• Plasma:1869
• Serum:1286
• PAX gene RNA:95
• RNA total:106
• Nasal lavage:280
• Urine: 200
• Exhaled Breath Condensate:140

Data Sets

Clinical: CRF/clinical, demographics

Molecular: viral pathogen testing, Blood RNA microarray, plasma metabolomics, plasma and nasal wash proteomics

Publications

• McClain et al. Longitudinal Analysis of Leukocyte Differentials in Peripheral Blood of Patients With Acute Respiratory Viral Infections. Journal of Clinical Virology (2019)
• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Burke et al. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine (2017)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)
• Rose et al. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One (2015)
• Carin et al. High-Dimensional Longitudinal Genomic Data: An Analysis Used for Monitoring Viral Infections. IEEE Signal Process Magazine (2012)
• Chen et al. Detection of Viruses via Statistical Gene Expression Analysis. IEEE (2010)
• Zaas et al. Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans. Cell Host & Microbe (2009)

Research Aims

Experimental Human Rhinovirus (HRV serotype 39) challenge study in healthy volunteers. The purpose of this study is to determine specific biomarker signatures predictive of an impending respiratory illness before the onset of symptoms. Participants were inoculated with HRV or saline control (blinded), and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed at the Duke University (2010).

Experimental Design

Subjects: 35

Timepoints: 10

Sample types:

• plasma:4421
• serum:2467
• PAXgene RNA:1073
• nasal lavage:1002
• nasal swab:7
• saliva:1613

Datasets

Clinical: demographics

Molecular: viral pathogen testing 

Publications

• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Burke et al. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine (2017)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)
• Rose et al. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One (2015)
• McClain et al. Longitudinal Analysis of Leukocyte Differentials in Peripheral Blood of Patients With Acute Respiratory Viral Infections. Journal of Clinical Virology (2013)
• Carin et al. High-Dimensional Longitudinal Genomic Data: An Analysis Used for Monitoring Viral Infections. IEEE Signal Processing Magazine (2012)
• Chen et al. Detection of Viruses via Statistical Gene Expression Analysis. IEEE (2011)
• Zaas et al. Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans. Cell Host & Microbe (2009)

Research Aims

Experimental Human Rhinovirus (HRV serotype 39) challenge study in healthy volunteers. The purpose of this study is to determine specific biomarker signatures and/or biometric measures predictive of an impending respiratory illness before the onset of symptoms. Participants were equipped with wearable physiologic monitoring devices and inoculated with HRV, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed in collaboration with the University of Virginia (2010).

Experimental Design

Subjects: 24

Timepoints: 4

Sample types:

• plasma:2588
• serum:69
• PAXgene RNA:76
• RNA total:428
• nasal lavage:985
• nasal swab:180
• other whole blood:346
• DNA total:19

Datasets

Clinical: CRF/clinical, demographics, symptom survey, cognitive survey, wearable device

Molecular: viral pathogen testing, microRNA transcriptomics, exome sequencing, plasma cytokines, proteomics

Publications

• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples.  BMC Bioinformatics (2016)
• Burke et al. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine (2017)

Research Aims

Experimental Influenza H1N1 (A/Brisbane/59/2007) challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with H1N1, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence (2008).

Experimental Design

Subjects: 31

Timepoints: 3

Sample types:

• plasma:3864
• serum:1651
• PAXgene RNA:966
• nasal lavage:505
• saliva:830

Datasets

Clinical: demographics

Molecular: viral pathogen testing, Blood RNA microarray, proteomics

Publications

• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)
• Rose et al. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One (2015)
• Zaas et al. A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine (2013)
• Woods et al. A Host Transcriptional Signature for Presymptomatic Detection of Infection in Humans Exposed to Influenza H1N1 or H3N2. PLoS One (2013)
• Carin et al. High-Dimensional Longitudinal Genomic Data: An Analysis Used for Monitoring Viral Infections. IEEE Signal Processing Magazine (2012)

Research Aims

Experimental Influenza H1N1 (A/Brisbane/59/2007) challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with H1N1, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. This study included an intervention group with anti-viral to compare effects of early treatment on clinical symptoms and molecular signature response (2009).

Experimental Design

Subjects: 55

Timepoints: 7

Sample types:

• plasma:7438
• serum:4013
• PAXgene RNA:2375
• nasal lavage:1068
• saliva:2195

Datasets

Clinical: demographics

Molecular: viral pathogen testing, Blood RNA microarray, proteomics

Publications

• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)

Research Aims

Experimental Influenza A/H1N1 challenge study in healthy volunteers. The purpose of this PROMETHEUS flu challenge study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were equipped with wearable physiologic monitoring devices and inoculated with HRV, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed in collaboration with Imperial College London (2017).

Experimental Design

Subjects: 39

Timepoints: 2

Sample types:

• buffy coat:662
• PBMC:811
• plasma:3278
• serum:307
• PAXgene RNA:1629
• other whole blood:9
• RNA total:538
• nasal lavage:4400
• nasal swab:477
• throat swab:541
• nascal scrape tissue:7
• feces:275

Datasets

Clinical: CRF/clinical data, demographics, symptom surveys, screening data, wearable phsiologic monitoring data

Molecular: viral pathogenic testing, host blood RNAseq, PBMC single-cell RNAseq, nasal tissue RNAseq, plasma and nasal wash cytokines, plasma proteomics, PBMC PTM proteomics, plasma p180 metabolomics, 

Research Aims

Experimental Influenza A (H3N2 A/Wisconsin/67/2005) challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with HRV, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence (2008).

Experimental Design

Subjects: 19

Timepoints: 3

Sample types:

• plasma:2896
• serum:1699
• PAXgene RNA:669
• nasal lavage:442
• urine: 344
• exhaled breath condensate: 198

Datasets

Clinical: demographics, microbiology, screening data

Molecular: viral pathogen testing, host blood RNA microarray, plasma and nasal cytokines

Publications

• Fourati et al. A Crowdsourced Anaylsis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Burke et al. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine (2017)
• Leonard et al. The Effective Rate of Influenza Reassortment is Limited During Human Infection. PLoS Pathogens (2017)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)
• Leonard et al. Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification. Journal of Virology (2016)
• Rose et al. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One (2015)
• McClain et al. Differential Evolution of Peripheral Cytokine Levels in Symptomatic and symptomatic responses to Experimental Influenza Virus Challenge. Clinical & Experimental Immunology (2015)
• Bagga et al. Comparing Influenza and RSV Viral and Disease Dynamics in Experimentally Infected Adults Predicts Clinical Effectiveness of RSV Antivirals. Antiviral Therapy (2013)
• McClain et al. Longitudinal Analysis of Leukocyte Differentials in Peripheral Blood of Patients With Acute Respiratory Viral Infections. Journal of Clinical Virology (2013)
• Zaas et al. A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine (2013)
• Woods et al. A Host Transcriptional Signature for Presymptomatic Detection of Infection in Humans Exposed to Influenza H1N1 or H3N2. PLoS One (2013)
• Carin et al. High-Dimensional Longitudinal Genomic Data: An Analysis Used for Monitoring Viral Infections. IEEE Signal Process Magazine (2012)
• Moody et al. H3N2 Influenza Infection Elicits More Cross-Reactive and Less Clonally Expanded Anti-Hemagglutinin Antibodies Than Influenza Vaccination. PLoS One (2011)
• Huang et al. Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection. PLoS Genetics (2011)
• Chen et al. Detection of Viruses via Statistical Gene Expression Analysis. IEEE (2011)
• Zaas et al. Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans. Cell Host & Microbe (2009)

Research Aims

Experimental Influenza A (H3N2 A/Wisconsin/67/2005) challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with HRV, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. This study included an early treatment group with anti-viral to compare effects of early (day one) versus late (day five) treatment on clinical symptoms and molecular signature response (2011).

Experimental Design

Subjects: 21

Timepoints: 2

Sample types: 

• pbmc:869
• plasma:3936
• serum:163
• PAXgene RNA:565
• nasal lavage:845
• nasal swab:1146
• saliva:734

Datasets

Clinical: demographics, microbiology, screening data

Molecular: viral pathogen testing, host blood RNA microarray, plasma and nasal cytokines

Publications

• Poore et al. A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies. Frontiers Microbiology (2018)
• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Burke et al. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection. EBioMedicine (2017)
• Leonard et al. The Effective Rate of Influenza Reassortment Is Limited During Human Infection. PLoS One Pathogens (2017)
• McClain et al. A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses. Open Forum Infectious Disease (2016)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)

Research Aims

Experimental Respiratory Syncytial Virus (RSV serotype A)  challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with RSV, a common respiratory pathogen, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence (2008).

Experimental Design

Subjects: 20

Timepoints: 21

Sample types:

• plasma:3272
• serum:1919
• PAXgene RNA:761
• nasal lavage:621
• urine:437
• exhaled breath condensate:258

Data Sets

Clinical: demographics

Molecular: viral pathogen testing, RNA microarray, viral load, metabolomics, proteomics

Publications

• Fourati et al. A Crowdsourced Analysis to Identify Ab Initio Molecular Signatures Predictive of Susceptibility to Viral Infection. Nature Communications (2018)
• Liu et al. An individualized predictor of health and disease using paired reference and target samples. BMC Bioinformatics (2016)
• Rose et al. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLos One (2015)
• McClain et al. Longitudinal Analysis of Leukocyte Differentials in Peripheral Blood of Patients With Acute Respiratory Viral Infections. Journal of Clinical Virology (2013)
• Bagga et al. Comparing Influenza and RSV Viral and Disease Dynamics in Experimentally Infected Adults Predicts Clinical Effectiveness of RSV Antivirals. Antiviral Therapy (2013)
• Carin et al. High-Dimensional Longitudinal Genomic Data: An Analysis Used for Monitoring Viral Infections. IEE Signal Processing Magazine (2012)
• Chen et al. Detection of Viruses via Statistical Gene Expression Analysis. IEEE (2011)
• Zaas et al. Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans. Cell Host & Microbe (2009)

Research Aims

Experimental Respiratory Syncytial Virus (RSV serotype A)  challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to influenza. Participants were inoculated with RSV, a common respiratory pathogen, and dense, longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed in collaboration with Imperial College London (2013).

Experimental Design

Subjects: 21

Timepoints: 1

Sample types:

• plasma:241
• PAXgene RNA:1109
• nasal lavage:542

Datasets

Clinical: CRF/clinical data, demographics

Molecular: viral pathogen testing, RNA microarray

Research Aims

Experimental ETEC Challenge (Enterotoxigenic E. coli; strain H10407) challenge study in healthy volunteers. The purpose of this study is to investigate the early pre-symptomatic period following exposure to ETEC. ETEC is a bacterial pathogen that causes diarrhea, largely in children living in developing countries and in travelers to those countries. Participants were inoculated with ETEC, and longitudinal sample and data collections were performed spanning pre-inoculation baseline through infection and convalescence. Subjects were enrolled and study was performed in collaboration with Johns Hopkins University (2011).

Experimental Design

Subjects: 31

Timepoints: 3

Sample types:

• plasma:2978
• PAXgene RNA:525

Datasets

Clinical: 

Molecular: 

Publications

• Yang et al. Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia Coli Infection in Humans. Journal of Infectious Diseases (2016)

Research Aims

Experimental Streptococcus pneumoniae challenge in non-human primate (NHP) model of respiratory infection. The purpose of this study is to develop and refine host-derived biomarkers and classification models capable of diagnosing bacterial pneumonia.

Experimental Design

Subjects: 27

Timepoints: 5

Sample types:

• plasma:467
• PAXgene RNA:258
• nasal swab:357
• other whole blood:595
• lavage, bronchoalveaolar:219
• urine:517

Datasets

Clinical: Clinical data including vitals, demographics, CBC, chest X-ray

Molecular: microbiology, viral pathogen testing, microRNA transcriptomics, plasma and BAL cytokines, plasma discovery and targeted proteomics

Publications

• Kraft et al. Development of a Novel Preclinical Model of Pneumococcal Pneumonia in Nonhuman Primates. American Journal of Respiratory Cell and Molecular Biology (2014)

Research Aims

This study aims to develop a predictive model and diagnostic test for detecting pre-symptomatic exposure and illness utilizing a unique index-cluster design. We prospectively enrolled undergraduate students at Duke University over five academic years. Students were monitored daily for the presence and severity of symptoms of respiratory tract infection. Index cases were identified by presence of symptoms and samples were collected and infection confirmed. We then identified close contacts who were presumed to be at increased risk of developing infection while under observation. We monitored each close contact for five days for symptoms and viral shedding, and collected blood and respiratory samples daily.

Experimental Design

Subjects: 1340

Timepoints: variable up to 31

Sample Types:

• plasma:22718
• serum:20432
• PAXgene RNA:6277
• nasal lavage:10141
• nasal swab:6547
• other whole blood:320
• RNA total:38
• urine:266
• DNA total:32
• saliva: 1090

Datasets

Clinical: CRF, demographics 

Molecular: pathogen testing, blood RNA microarray, plasma cytokines 

Publications

• McClain et al. A blood-based host gene expression assay for early detection of respiratory viral infection: an index-cluster prospective cohort study. The Lancet Infectious Diseases (2020)

Research Aims

This study investigates the pre-symptomatic period after potential exposure to an infectious agent. Participants include families with young children or families with an adult as a health care worker. Participants are monitored daily through electronic symptom survey and wearable physiologic monitoring devices. Upon illness event, biospecimens and additional data are collected from symptomatic index case, and close family contacts are monitored and samples collected daily to identify individuals as they transition from exposure to naturally-acquired infection. We use these well-characterized cases and chains of transmission to identify and characterize the contagious phenotype, and to validate wearable data and other biomarkers of impending ARI.

Experimental Design

Subjects: 84

Timepoints: variable 

Sample types:

• PAXgene RNA:870
• plasma:1061
• serum:431
• urine:6
• nasal swab:2077
• buffy coat:55

Datasets

Clinical: CRF, demographics, symptom survey, wearable physiologic monitoring devices

Molecular: Pathogen etiology testing

Research Aims

This study will develop biomarker assays that are capable of distinguishing viral versus bacterial infection using the host response. The spectrum of pathogens to be explored ranges from common respiratory illnesses present in the continental United States to emerging global infections, and includes international cohort collections from Tanzania, Nicaragua, Sri Lanka and Nepal.

Experimental Design

Subjects: 2582

Timepoints: 2

Sample types:

• serum:421
• PAXgene RNA:2895
• RNA total:266
• nasal swab:261
• other whole blood:510
• urine:458

Datasets

Clinical: CRF/clinical data, demographics, clinical adjudication

Molecular: viral pathogen testing, microRNA transcriptomics, nanostring RNA, serum discovery and targeted proteomics, serum p180 metabolites

Research Aims

The overall goal of this project is to utilize host-derived biomarkers to define the etiology and severity of acute respiratory illness in at-risk hosts with Cystic Fibrosis and/or lung transplantation. Through examination of host molecular responses, we will develop and refine biomarker signatures capable of diagnosing acute respiratory infection, identifying broad pathogen class, distinguishing infection from rejection, and predicting disease severity.

Experimental Design

Subjects: 106

Timepoints: 1

Sample types:

• plasma:68
• serum:325
• nasal swab:438
• PAXgene RNA:318

Datasets

Clinical: CRF/clinical data, demographics, clinical adjudication

Molecular: microbiology, blood RNAseq, plasma cytokines, pathogen etiology test, procalcitonin

Research Aims

To work towards developing a clinico-molecular signature comprised of clinical variables and host response profiles (transcriptome and proteome) that 1) distinguishes VAP from non-infected ventilated subjects, 2) distinguishes VAP from other types of HAI, and 3) identifies patients in the pre-symptomatic phase who will go on to develop VAP.

Experimental Design

Subjects: 220

Timepoints: 10

Sample types:

• plasma:5599
• serum:2959
• PAXgene RNA:715
• nasal lavage:10
• nasal swab:787
• whole blood, EDTA:178
• DNA total:1
• lavage, bronchoalveaolar: 68
• urine:1177

Datasets

Clinical: CRF, EHR data, demographics, clinical adjudication

Molecular: MicroRNA Transcriptopmics, blood RNAseq, blood miRNAseq, plasma procalcitonin, plasma metabolomics

Research Aims

An experimental challenge study involving administration of different aspirin doses or ticagrelor to healthy volunteers, patients with diabetes or coronary artery disease with longitudinal data and sample collections to investigate potential role of platelet aggregation in atherothrombotic risk. Using this approach, we successfully performed peripheral blood or platelet gene expression profiling methods to identify genomic pathways indicative of the response to antiplatelet agents.

Experimental Design

Subjects: 203

Timepoints: variable up to 5

Sample types: 

• plasma:6655
• serum:3875
• PAXgene RNA:2826
• buffy coat:718
• feces:339

Datasets

Clinical: CRF/clinical data, platelet function assays

Molecular: Peripheral blood microarrays 

Publications

• Friede, et al. Influence of Sex on Platelet Reactivity in Response to Aspirin. J Am Heart Assoc. (2020)
• Poore et al. A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies. Frontiers in Microbiology (2018)
• Voora et al. Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer. EBioMedicine (2016)
• Voora et al. Aspirin Exposure Reveals Novel Genes Associated With Platelet Function and Cardiovascular Events. Journal of the American College of Cardiology (2013)
• Ahn et al. Gene Expression-Based Classifiers Identify Staphylococcus Aureus Infection in Mice and Humans. PLoS One (2013)
• Voora et al. Time-dependent Changes in non-COX-1-dependent Platelet Function With Daily Aspirin Therapy. Journal of Thrombosis and Thrombolysis (2012)

Research Aims

This pilot study enrolled patients with and without a history of statin-associated myopathy in order to collect a skeletal muscle biopsy and blood for ex vivo testing.  The primary study aims are 1) to characterize myobundle performance in patients with and without a history of statin-induced myopathy, and 2) to identify molecular changes associated with ex vivo statin-induced myopathy.  

Experimental Design

Subjects: 42

Timepoints: 2

Sample types:

• plasma:135
• PAXgene RNA:123
• whole blood, EDTA:41
• fresh tissue:557

Datasets

Clinical: Demographics, comorbidities, meds, lab data, tissue-engineered myobundle muscle force and immunofluorescence data

Molecular: Plasma metabolomics, tissue-engineered myobundle and media metabolomics

Research Aims

PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) is a prospective, randomized trial comparing two diagnostic testing strategies for coronary artery disease (CAD) - coronary computed tomographic angiography (CTA) relative to standard-of-care functional testing.

Experimental Design

Subjects: 7867

Timepoints: variable

Sample types:

• plasma:20536
• serum:34492
• whole blood, EDTA:2824
• PAXgene blood RNA:8069
• RNA total:4426
• RNA:4017
• packed blood cells:2873

Datasets

Clinical: CRF/clinical, demographics, labs, meds, comorbidities, outcomes, anatomic imaging

Molecular: plasma proteomics, plasma metabolomics, blood RNAseq

Publications

• Meyersohn et al. Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease. Clinical Gastroenterology and Hepatology (2020)
• Sheldon et al. Discordances between predicted and actual risk in obese patients with suspected cardiac ischaemia. Heart (2020)
• Jang et al. Predictive Model for High-Risk Coronary Artery Disease. Circulation: Cardiovascular Imaging (2019)
• Januzzi et al. High-Sensitivity Troponin I and Coronary Computed Tomography in Symptomatic Outpatients With Suspected CAD: Insights From the PROMISE Trial. JACC: Cardiovascular Imaging (2019)
• Januzzi et al. Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain. Journal of the American College of Cardiology (2019)
• Lowenstern et al. Age-Related Differences in the Noninvasive Evaluation for Possible Coronary Artery Disease: Insights From the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial. JAMA Cardiology (2019)
• Pagidipati et al. Sex differences in management and outcomes of patients with stable symptoms suggestive of coronary artery disease: Insights from the PROMISE trial. American Heart Journal (2019)
• Sharma et al. Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease. Journal of the American College of Cardiology (2019)
• Sheldon et al. Effects of obesity on noninvasive test results in patients with suspected cardiac ischemia: Insights from the PROMISE trial. Journal of Cardiovascular Computed Tomography (2019)
• Ferencik et al. Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial. JAMA Cardiology (2018)
• Lu et al. Central Core Laboratory versus Site Interpretation of Coronary CT Angiography: Agreement and Association with Cardiovascular Events in the PROMISE Trial. Radiology (2018)
• Budoff et al. Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Circulation (2017)
• Fordyce et al. Identification of Patients With Stable Chest Pain Deriving Minimal Value From Noninvasive Testing: The PROMISE Minimal-Risk Tool, A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiology (2017)
• Hoffmann et al. Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Circulation (2017)
• Ladapo et al. Quantifying sociodemographic and income disparities in medical therapy and lifestyle among symptomatic patients with suspected coronary artery disease: a cross-sectional study in North America. BMJ Open (2017)
• Lu et al. Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose. Journal of Cardiovascular Computed Tomography (2017)
• Sharma et al. Impact of Diabetes Mellitus on the Evaluation of Stable Chest Pain Patients: Insights From the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Trial. Journal of the American Heart Association (2017)
• Ladapo et al. Changes in Medical Therapy and Lifestyle After Anatomical or Functional Testing for Coronary Artery Disease. Journal of the American Heart Association (2016)
• Mark et al. Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease. Annals of Internal Medicine (2016)
• Mark et al. Quality-of-Life Outcomes With Anatomic Versus Functional Diagnostic Testing Strategies in Symptomatic Patients With Suspected Coronary Artery Disease: Results From the PROMISE Randomized Trial. Circulation (2016)
• Douglas et al. Outcomes of anatomical versus functional testing for coronary artery disease. The New England Journal of Medicine (2016)
• Douglas et al. PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial. American Heart Journal (2014)

Research Aims

STRENGTH (Statin Response Examined by Genetic Haplotype Markers) is a randomized, open label pharmacogenetic study of statin efficacy and safety in outpatient participants with hypercholesterolemia.

Experimental Design

Subjects: 38

Timepoints: 2

Sample types:

• plasma:231

Datasets

Clinical: CRF/clinical data, demographics

Molecular: plasma metabolomics

Research Aims

DoD-funded study including longitudinal sample and data collections from research participants with severe traumatic brain injuries (TBIs). Research aims include development of blood-based biomarker signatures capable in aiding the diagnosis and management of epilepsy and prognosis of recurrence following first seizure event. 

Experimental Design

Subjects: 45

Timepoints: variable up to 2 

Sample types:

• plasma:222
• PAXgene RNA:33
• RNA total:6
• whole blood, EDTA:89

Datasets

Clinical: CRF, demographics, EHR data including EEG, MRI demographics

Molecular: MicroRNA Transcriptopmics, microbiology, cytokines

Research Aims

To examine the effects of sleep deprivation in healthy subjects by observing their changes in cognition and assessing the correlation between different factors — including demographic variables and biomarkers — with physiological response to sleep deprivation. 

Experimental Design

Subjects: 18

Timepoints: 1

Sample types:

• plasma:157
• PAXgene RNA:38
• whole blood, EDTA:36