Scholars@Duke
Chi Wei Cliburn Chan

Chi Wei Cliburn Chan

Professor of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Integrative Genomics
cliburn.chan@duke.edu
Duke Box 2721, Durham, NC 27710
2424 Erwin Road Ste 1102, 11078 Hock Plaza Duke Box 2721, Durham, NC 27705

Selected Publications

The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques.

Journal Article Sci Transl Med · March 12, 2025 Congenital cytomegalovirus (cCMV) is the leading infectious cause of neonatal neurological impairment worldwide, but the viral factors enabling vertical spread across the placenta remain undetermined. The pentameric complex (PC), composed of the subunits g ... Full text Link to item Cite

Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.

Journal Article Nat Commun · January 31, 2025 Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily ... Full text Link to item Cite

Modeling BK Virus Infection in Renal Transplant Recipients.

Journal Article Viruses · December 31, 2024 Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1 ... Full text Open Access Link to item Cite

Prevalence of and Risk Factors for Liver Enzyme Elevation After Hepatitis C Virologic Cure.

Journal Article J Viral Hepat · December 2024 A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single-centre retrospective coh ... Full text Link to item Cite

B-Lightning: using bait genes for marker gene hunting in single-cell data with complex heterogeneity.

Journal Article Brief Bioinform · November 22, 2024 In single-cell studies, cells can be characterized with multiple sources of heterogeneity (SOH) such as cell type, developmental stage, cell cycle phase, activation state, and so on. In some studies, many nuisance SOH are of no interest, but may confound t ... Full text Link to item Cite

The Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?

Journal Article AIDS Res Hum Retroviruses · October 2024 Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human h ... Full text Link to item Cite

Engagement in Care, Awareness, and Interest in Long-Acting Injectable Anti-Retroviral Therapy.

Journal Article AIDS Behav · October 2024 Long Acting Injectable (LAI) therapy to treat HIV is an alternative to daily oral medications. The success of early roll-out of LAI to eligible patients requires a better understanding of patients' awareness and interest in this novel therapy. We administe ... Full text Link to item Cite

Assessing the impact of autologous virus neutralizing antibodies on viral rebound time in postnatally SHIV-infected ART-treated infant rhesus macaques.

Journal Article Epidemics · September 2024 While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the siz ... Full text Link to item Cite

SifiNet: a robust and accurate method to identify feature gene sets and annotate cells.

Journal Article Nucleic Acids Res · May 22, 2024 SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clusterin ... Full text Link to item Cite

Multivalent cytomegalovirus glycoprotein B nucleoside modified mRNA vaccines did not demonstrate a greater antibody breadth.

Journal Article NPJ Vaccines · February 20, 2024 Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% ef ... Full text Link to item Cite

Coarsened Mixtures of Hierarchical Skew Normal Kernels for Flow and Mass Cytometry Analyses

Journal Article Bayesian Analysis · January 1, 2024 Cytometry is the standard multi-parameter assay for measuring single cell phenotype and functionality. It is commonly used for quantifying the relative frequencies of cell subsets in blood and disaggregated tissues. A typical analysis of cytometry data inv ... Full text Cite

Maternal immunity shapes biomarkers of germinal center development in HIV-exposed uninfected infants.

Journal Article Frontiers in immunology · January 2024 IntroductionHIV-exposed uninfected (HEU) infants exhibit elevated pro-inflammatory biomarkers that persist after birth. However, comprehensive assessments of bioprofiles associated with immune regulation and development in pregnant women with HIV ... Full text Cite

A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

Journal Article PLoS One · 2024 To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bN ... Full text Link to item Cite

Cocaine Use Prediction With Tensor-Based Machine Learning on Multimodal MRI Connectome Data.

Journal Article Neural Comput · December 12, 2023 This letter considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study used functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was ... Full text Link to item Cite

Immune Phenotype and Postoperative Complications After Elective Surgery.

Journal Article Ann Surg · December 1, 2023 OBJECTIVES: To characterize and quantify accumulating immunologic alterations, pre and postoperatively in patients undergoing elective surgical procedures. BACKGROUND: Elective surgery is an anticipatable, controlled human injury. Although the human respon ... Full text Link to item Cite

Evidence2Practice (E2P): Leveraging Implementation Science to Promote Careers in HIV Research Among Students From Historically Black Colleges and Universities.

Journal Article J Acquir Immune Defic Syndr · October 1, 2023 BACKGROUND: The HIV research workforce is not representative of populations most affected by the epidemic. Innovative educational programs are needed to motivate diverse student populations to pursue careers in HIV research. METHODS: The Duke University Ce ... Full text Open Access Link to item Cite

Mathematical Modeling of Rhesus Cytomegalovirus Transplacental Transmission in Seronegative Rhesus Macaques.

Journal Article Viruses · October 1, 2023 Approximately 0.7% of infants are born with congenital cytomegalovirus (CMV), making it the most common congenital infection. About 1 in 5 congenitally infected babies will suffer long-term sequelae, including sensorineural deafness, intellectual disabilit ... Full text Link to item Cite

Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model.

Journal Article PLoS Pathog · October 2023 Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity co ... Full text Link to item Cite

Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci.

Journal Article Cell Rep · August 29, 2023 Chromatin accessibility fundamentally governs gene expression and biological response programs that can be manipulated by pathogens. Here we capture dynamic chromatin landscapes of individual B cells during Epstein-Barr virus (EBV) infection. EBV+ cells th ... Full text Link to item Cite

Leveraging preclinical study designs to close gaps in vaccine development for perinatal pathogens.

Journal Article J Exp Med · July 3, 2023 Vaccines to perinatal pathogens are critical for both reducing the burden of endemic pathogens and preparing for the next pandemic. Although they are often at greater risk of severe disease from infection, pregnant people and children are routinely margina ... Full text Link to item Cite

Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV.

Journal Article JCI Insight · March 22, 2023 Rhesus cytomegalovirus-based (RhCMV-based) vaccine vectors induce immune responses that protect ~60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction of effector memory-based (EM-biased) CD8+ T cells recognizing SIV pep ... Full text Link to item Cite

TEAM: A MULTIPLE TESTING ALGORITHM ON THE AGGREGATION TREE FOR FLOW CYTOMETRY ANALYSIS.

Journal Article Ann Appl Stat · March 2023 In immunology studies, flow cytometry is a commonly used multivariate single-cell assay. One key goal in flow cytometry analysis is to detect the immune cells responsive to certain stimuli. Statistically, this problem can be translated into comparing two p ... Full text Link to item Cite

Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.

Journal Article J Neurovirol · February 2023 This study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and ne ... Full text Link to item Cite

A simple model for viral decay dynamics and the distribution of infected cell life spans in SHIV-infected infant rhesus macaques.

Journal Article Math Biosci · February 2023 The dynamics of HIV viral load following the initiation of antiretroviral therapy is not well-described by simple, single-phase exponential decay. Several mathematical models have been proposed to describe its more complex behavior, the most popular of whi ... Full text Link to item Cite

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Conference Frontiers in Immunology · January 1, 2023 Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs re ... Full text Cite

Biomarkers detected in cord blood predict vaccine responses in young infants.

Journal Article Front Immunol · 2023 INTRODUCTION: Factors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that b ... Full text Link to item Cite

Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering.

Journal Article Genome Biol · December 27, 2022 Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clusterin ... Full text Link to item Cite

Experiential Learning Methods for Biostatistics Students: A Model for Embedding Student Interns in Academic Health Centers.

Journal Article Stat · December 2022 This manuscript describes an experiential learning program for future collaborative biostatisticians (CBs) developed within an academic medical center. The program is a collaborative effort between the Biostatistics, Epidemiology, and Research Design (BERD ... Full text Link to item Cite

NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health.

Journal Article Nature aging · December 2022 Cells respond to many stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a proinflammatory senescence-associated secretory phenotype. The heterogeneity of senescent cells (SnCs) and senescence-associated secretor ... Full text Cite

Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus.

Journal Article J Infect Dis · November 1, 2022 BACKGROUND: Human cytomegalovirus (HCMV) is the most common infectious complication of organ transplantation and cause of birth defects worldwide. There are limited therapeutic options and no licensed vaccine to prevent HCMV infection or disease. To inform ... Full text Link to item Cite

Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.

Journal Article Sci Adv · September 23, 2022 To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibod ... Full text Link to item Cite

Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.

Journal Article Cell Rep · August 30, 2022 Epstein-Barr virus infection of B lymphocytes elicits diverse host responses via well-adapted transcriptional control dynamics. Consequently, this host-pathogen interaction provides a powerful system to explore fundamental processes leading to consensus fa ... Full text Link to item Cite

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

Journal Article Ann Surg · June 1, 2022 OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the system ... Full text Link to item Cite

HLA Loci and Recurrence of Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplantation.

Journal Article Transplant Direct · October 2021 UNLABELLED: Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mec ... Full text Open Access Link to item Cite

Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries.

Journal Article G3 (Bethesda, Md.) · October 2021 RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper se ... Full text Cite

Pre-existing immunity to cytomegalovirus in macaques influences human CMV vaccine responses in preclinical models.

Journal Article Vaccine · September 7, 2021 Development of a human cytomegalovirus (HCMV) vaccine is a Tier 1 priority by the National Institutes of Medicine, as HCMV is the most common congenital infection globally and most frequent infectious complication in transplant patients. Relevant preclinic ... Full text Link to item Cite

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Journal Article Sci Rep · July 14, 2021 A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutate ... Full text Link to item Cite

Prognosis and treatment effects of HIV-associated talaromycosis in a real-world patient cohort.

Journal Article Med Mycol · April 6, 2021 Talaromycosis is a leading cause of AIDS-associated opportunistic infections and death in Southeast Asia. We have recently shown in the Itraconazole versus Amphotericin for Talaromycosis (IVAP) trial that induction therapy with amphotericin B reduced morta ... Full text Open Access Link to item Cite

Reduced plasmablast frequency is associated with seronegative myasthenia gravis.

Journal Article Muscle & nerve · April 2021 BackgroundThe immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG.MethodsWe performed high-dimensional flow cytomet ... Full text Cite

Ontology-guided segmentation and object identification for developmental mouse lung immunofluorescent images.

Journal Article BMC Bioinformatics · February 23, 2021 BACKGROUND: Immunofluorescent confocal microscopy uses labeled antibodies as probes against specific macromolecules to discriminate between multiple cell types. For images of the developmental mouse lung, these cells are themselves organized into densely p ... Full text Link to item Cite

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults.

Journal Article Sci Rep · February 4, 2021 Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet th ... Full text Open Access Link to item Cite

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Journal Article American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · February 2021 Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Ped ... Full text Cite

Machine learning prediction of neurocognitive impairment among people with HIV using clinical and multimodal magnetic resonance imaging data.

Journal Article J Neurovirol · February 2021 Diagnosis of HIV-associated neurocognitive impairment (NCI) continues to be a clinical challenge. The purpose of this study was to develop a prediction model for NCI among people with HIV using clinical- and magnetic resonance imaging (MRI)-derived feature ... Full text Link to item Cite

Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines.

Journal Article Elife · January 27, 2021 Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein-Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell t ... Full text Link to item Cite

Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Journal Article Front Immunol · 2021 Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. Howe ... Full text Link to item Cite

FlowKit: A Python Toolkit for Integrated Manual and Automated Cytometry Analysis Workflows.

Journal Article Frontiers in immunology · January 2021 An important challenge for primary or secondary analysis of cytometry data is how to facilitate productive collaboration between domain and quantitative experts. Domain experts in cytometry laboratories and core facilities increasingly recognize the need f ... Full text Open Access Cite

Simian-Human Immunodeficiency Virus SHIV.C.CH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4+ T Cells.

Journal Article J Virol · December 22, 2020 Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) continues to cause new pediatric cases of infection through breastfeeding, a setting where it is not always possible to initiate early antiretroviral therapy (ART). Without novel i ... Full text Link to item Cite

Antibody binding to native cytomegalovirus glycoprotein B predicts efficacy of the gB/MF59 vaccine in humans.

Journal Article Sci Transl Med · November 4, 2020 Human cytomegalovirus (CMV) is the most common infectious cause of infant brain damage and posttransplant complications worldwide. Despite the high global burden of disease, vaccine development to prevent infection remains hampered by challenges in generat ... Full text Link to item Cite

A randomized phase 2 trial of pembrolizumab versus pembrolizumab and acalabrutinib in patients with platinum-resistant metastatic urothelial cancer.

Journal Article Cancer · October 15, 2020 BACKGROUND: Inhibition of the programmed cell death protein 1 (PD-1) pathway has demonstrated clinical benefit in metastatic urothelial cancer (mUC); however, response rates of 15% to 26% highlight the need for more effective therapies. Bruton tyrosine kin ... Full text Open Access Link to item Cite

Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.

Journal Article Am J Hematol · June 2020 Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical ... Full text Link to item Cite

Flow cytometry in cancer immunotherapy: Applications, quality assurance, and future

Chapter · January 1, 2020 The recent success and enormous potential of immune checkpoint modulation demonstrate how powerful T-cells are in controlling tumor cell growth; with checkpoint blockade antibodies, antitumor effects mostly rely on the functional release of preexisting tum ... Full text Cite

Flow Cytometry Characterization of Cerebrospinal Fluid Monocytes in Patients With Postoperative Cognitive Dysfunction: A Pilot Study.

Journal Article Anesth Analg · November 2019 Animal models suggest postoperative cognitive dysfunction may be caused by brain monocyte influx. To study this in humans, we developed a flow cytometry panel to profile cerebrospinal fluid (CSF) samples collected before and after major noncardiac surgery ... Full text Open Access Link to item Cite

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model.

Journal Article mBio · September 5, 2019 To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. Identifying clinical predictors of the time to viral rebound upon ART interruption w ... Full text Link to item Cite

Tenofovir Has Minimal Effect on Biomarkers of Bone Health in Youth with HIV Receiving Initial Antiretroviral Therapy.

Journal Article AIDS Res Hum Retroviruses · August 2019 Both HIV infection and tenofovir disoproxil fumarate (TDF) treatment adversely impact bone metabolism and may lead to osteopenia, which has critical implications for youth with HIV (YWH). This study evaluates changes in the biomarkers of bone metabolism an ... Full text Link to item Cite

Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.

Journal Article SLAS Discov · July 2019 Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on id ... Full text Link to item Cite

fastJT: An R package for robust and efficient feature selection for machine learning and genome-wide association studies.

Journal Article BMC Bioinformatics · June 13, 2019 BACKGROUND: Parametric feature selection methods for machine learning and association studies based on genetic data are not robust with respect to outliers or influential observations. While rank-based, distribution-free statistics offer a robust alternati ... Full text Link to item Cite

The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction.

Journal Article J Am Geriatr Soc · April 2019 BACKGROUND/OBJECTIVES: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of ... Full text Open Access Link to item Cite

Establishment of normative ranges of the healthy human immune system with comprehensive polychromatic flow cytometry profiling.

Journal Article PLoS One · 2019 Existing normative flow cytometry data have several limitations including small sample sizes, incompletely described study populations, variable flow cytometry methodology, and limited depth for defining lymphocyte subpopulations. To overcome these issues, ... Full text Open Access Link to item Cite

bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens.

Journal Article Bioinformatics · October 15, 2018 SUMMARY: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings am ... Full text Link to item Cite

Bayesian Multi-Plate High-Throughput Screening of Compounds.

Journal Article Sci Rep · June 22, 2018 High-throughput screening of compounds (chemicals) is an essential part of drug discovery, involving thousands to millions of compounds, with the purpose of identifying candidate hits. Most statistical tools, including the industry standard B-score method, ... Full text Link to item Cite

Effect of endotoxin and alum adjuvant vaccine on peanut allergy.

Journal Article J Allergy Clin Immunol · February 2018 Full text Link to item Cite

Facilitating the Calculation of the Efficient Score Using Symbolic Computing.

Journal Article Am Stat · 2018 The score statistic continues to be a fundamental tool for statistical inference. In the analysis of data from high-throughput genomic assays, inference on the basis of the score usually enjoys greater stability, considerably higher computational efficienc ... Full text Link to item Cite

LungMAP: The Molecular Atlas of Lung Development Program.

Journal Article Am J Physiol Lung Cell Mol Physiol · November 1, 2017 The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by i ... Full text Link to item Cite

Assessing the satisfaction and burden within an academic animal care and use program.

Journal Article FASEB J · September 2017 Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, ... Full text Link to item Cite

Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells.

Journal Article Frontiers in immunology · January 2017 Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual la ... Full text Cite

Preface

Chapter · January 1, 2017 Full text Cite

Quantitative methods and bayesian models for flow cytometry analysis in HIV/AIDS research

Chapter · January 1, 2017 Flow cytometry is a multiparameter single-cell assay ubiquitous in HIV/AIDS clinical and research settings for evaluating the immune response to the virus, therapy, and vaccination. In clinical practice, flow cytometry is used to monitor the CD4 and CD8 T ... Full text Cite

Characterization of Simian Immunodeficiency Virus Variants Anatomically Compartmentalized in Plasma and Milk in Chronically Infected African Green Monkeys.

Journal Article J Virol · October 1, 2016 UNLABELLED: Unlike human immunodeficiency virus type 1 (HIV-1)-infected humans, African-origin, natural simian immunodeficiency virus (SIV) hosts, such as African green monkeys (AGMs), sustain nonpathogenic SIV infections and rarely vertically transmit SIV ... Full text Link to item Cite

Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.

Journal Article Arterioscler Thromb Vasc Biol · February 2016 OBJECTIVE: Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional ana ... Full text Link to item Cite

Discriminative variable subsets in Bayesian classification with mixture models, with application in flow cytometry studies.

Journal Article Biostatistics · January 2016 We discuss the evaluation of subsets of variables for the discriminative evidence they provide in multivariate mixture modeling for classification. The novel development of Bayesian classification analysis presented is partly motivated by problems of desig ... Full text Link to item Cite

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.

Journal Article Am J Respir Crit Care Med · January 1, 2016 RATIONALE: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed ... Full text Link to item Cite

Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.

Journal Article J Med Chem · November 12, 2015 HIV-1-latency-reversing agents, such as histone deacetylase inhibitors (HDACIs), were ineffective in reducing latent HIV-1 reservoirs ex vivo using CD4 cells from patients as a model. This deficiency poses a challenge to current pharmacological approaches ... Full text Link to item Cite

Data analysis as a source of variability of the HLA-peptide multimer assay: from manual gating to automated recognition of cell clusters.

Journal Article Cancer Immunol Immunother · May 2015 Multiparameter flow cytometry is an indispensable method for assessing antigen-specific T cells in basic research and cancer immunotherapy. Proficiency panels have shown that cell sample processing, test protocols and data analysis may all contribute to th ... Full text Link to item Cite

Flow cytometry in cancer immunotherapy: Applications, quality assurance, and future

Journal Article · January 1, 2015 Cancer immunotherapy seeks to elicit or augment the antitumor immune response in a patient in order to enlist the help of the patient’s own immune system for tumor control. In this context, immune monitoring provides evidence of immunogenicity, guides the ... Full text Cite

Setting objective thresholds for rare event detection in flow cytometry.

Journal Article J Immunol Methods · July 2014 The accurate identification of rare antigen-specific cytokine positive cells from peripheral blood mononuclear cells (PBMC) after antigenic stimulation in an intracellular staining (ICS) flow cytometry assay is challenging, as cytokine positive events may ... Full text Open Access Link to item Cite

Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays.

Journal Article J Immunol Methods · July 2014 The External Quality Assurance Program Oversight Laboratory (EQAPOL) Flow Cytometry Program assesses the proficiency of NIH/NIAID/DAIDS-supported and potentially other interested research laboratories in performing Intracellular Cytokine Staining (ICS) ass ... Full text Open Access Link to item Cite

High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

Journal Article Sci Rep · April 23, 2014 Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide e ... Full text Link to item Cite

Managing Multi-center Flow Cytometry Data for Immune Monitoring.

Journal Article Cancer Inform · 2014 With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a s ... Full text Link to item Cite

Hierarchical Bayesian mixture modelling for antigen-specific T-cell subtyping in combinatorially encoded flow cytometry studies.

Journal Article Stat Appl Genet Mol Biol · June 2013 Novel uses of automated flow cytometry technology for measuring levels of protein markers on thousands to millions of cells are promoting increasing need for relevant, customized Bayesian mixture modelling approaches in many areas of biomedical research an ... Full text Link to item Cite

Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion.

Journal Article Ann Surg Oncol · April 2013 BACKGROUND: Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity mela ... Full text Link to item Cite

Critical assessment of automated flow cytometry data analysis techniques.

Journal Article Nat Methods · March 2013 Traditional methods for flow cytometry (FCM) data processing rely on subjective manual gating. Recently, several groups have developed computational methods for identifying cell populations in multidimensional FCM data. The Flow Cytometry: Critical Assessm ... Full text Link to item Cite

A model for migratory B cell oscillations from receptor down-regulation induced by external chemokine fields.

Journal Article Bull Math Biol · January 2013 A long-standing paradigm in B cell immunology is that effective somatic hypermutation and affinity maturation require cycling between the dark zone and light zone of the germinal center. The cyclic re-entry hypothesis was first proposed based on considerat ... Full text Link to item Cite

A Model for Migratory B Cell Oscillations from Receptor Down-Regulation Induced by External Chemokine Fields

Journal Article Bulletin of Mathematical Biology · 2013 A long-standing paradigm in B cell immunology is that effective somatic hypermutation and affinity maturation require cycling between the dark zone and light zone of the germinal center. The cyclic re-entry hypothesis was first proposed based on considerat ... Full text Cite

Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

Journal Article PLoS Comput Biol · 2013 Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less). Stan ... Full text Link to item Cite

Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis.

Journal Article Am J Transplant · March 2011 Cytomegalovirus (CMV) is a common opportunistic infection after lung transplant. Despite effective antiviral medications to treat CMV, invasive CMV disease contributes to lung allograft dysfunction and worse survival. Efforts to prevent CMV have led to the ... Full text Link to item Cite

Optimization of a highly standardized carboxyfluorescein succinimidyl ester flow cytometry panel and gating strategy design using discriminative information measure evaluation.

Journal Article Cytometry A · December 2010 The design of a panel to identify target cell subsets in flow cytometry can be difficult when specific markers unique to each cell subset do not exist, and a combination of parameters must be used to identify target cells of interest and exclude irrelevant ... Full text Link to item Cite

Rejoinder

Journal Article Bayesian Analysis · December 1, 2010 We thank the discussants, Fabio Rigat and Nick Whiteley, for their insightful and positive comments. They suggest a number of potential directions for extension of the work and raise connections with other research. We address the points they raise in conn ... Full text Cite

Modeling flow cytometry data for cancer vaccine immune monitoring.

Journal Article Cancer Immunol Immunother · September 2010 Flow cytometry (FCM) is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. In all these applications, the challenge is to detect extremely rare cell subse ... Full text Link to item Cite

Understanding GPU Programming for Statistical Computation: Studies in Massively Parallel Massive Mixtures.

Journal Article J Comput Graph Stat · June 1, 2010 This article describes advances in statistical computation for large-scale data analysis in structured Bayesian mixture models via graphics processing unit (GPU) programming. The developments are partly motivated by computational challenges arising in fitt ... Full text Open Access Link to item Cite

Selection sampling from large data sets for targeted inference in mixture modeling

Journal Article Bayesian Analysis · 2010 One of the challenges in using Markov chain Monte Carlo for model analysis in studies with very large datasets is the need to scan through the whole data at each iteration of the sampler, which can be computationally prohibitive. Several approaches have be ... Full text Cite

Statistical mixture modeling for cell subtype identification in flow cytometry.

Journal Article Cytometry A · August 2008 Statistical mixture modeling provides an opportunity for automated identification and resolution of cell subtypes in flow cytometric data. The configuration of cells as represented by multiple markers simultaneously can be modeled arbitrarily well as a mix ... Full text Link to item Cite

Flow: Statistics, visualization and informatics for flow cytometry.

Journal Article Source Code Biol Med · June 17, 2008 Flow is an open source software application for clinical and experimental researchers to perform exploratory data analysis, clustering and annotation of flow cytometric data. Flow is an extensible system that offers the ease of use commonly found in commer ... Full text Link to item Cite

The Multiscale Systems Immunology project: software for cell-based immunological simulation.

Journal Article Source Code Biol Med · April 28, 2008 BACKGROUND: Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent base ... Full text Open Access Link to item Cite

Reconstruction of cell population dynamics using CFSE.

Journal Article BMC Bioinformatics · June 12, 2007 BACKGROUND: Quantifying cell division and death is central to many studies in the biological sciences. The fluorescent dye CFSE allows the tracking of cell division in vitro and in vivo and provides a rich source of information with which to test models of ... Full text Link to item Cite

Oscillations in the immune system.

Journal Article Immunol Rev · April 2007 Oscillations are surprisingly common in the immune system, both in its healthy state and in disease. The most famous example is that of periodic fevers caused by the malaria parasite. A number of hereditary disorders, which also cause periodic fevers, have ... Full text Link to item Cite

Spatiotemporal programming of a simple inflammatory process.

Journal Article Immunol Rev · April 2007 Inflammatory processes are essential for recruiting leukocytes to the site of infection in sufficient numbers and for initiating adaptive immunity. Unresolved inflammation, however, can cause serious damage to host tissues and indeed is known to contribute ... Full text Link to item Cite

Computational immunology--from bench to virtual reality.

Journal Article Ann Acad Med Singap · February 2007 Drinking from a fire-hose is an old cliché for the experience of learning basic and clinical sciences in medical school, and the pipe has been growing fatter at an alarming rate. Of course, it does not stop when one graduates; if anything, both the researc ... Link to item Cite

Cytotoxic killing and immune evasion by repair

Journal Article Journal of Statistical Physics · January 1, 2007 The interaction between the immune system and pathogens is a complex one, with pathogens constantly developing new ways of evading destruction by the immune system. The immune system's task is made even harder when the pathogen in question is an intra-cell ... Full text Cite

Knockdown of mouse VCAM-1 by vector-based siRNA.

Journal Article Transpl Immunol · November 2006 Graft rejection is critically dependent on the recruitment of leukocytes via adhesion molecules on the endothelium, and inhibition of these interactions can prolong graft survival. We have therefore developed an approach using siRNA to inhibit the expressi ... Full text Link to item Cite

The evolving role of gene-based treatment in surgery.

Journal Article Br J Surg · December 2005 Featured Publication BACKGROUND: The completion of the sequencing of the human genome in 2003 marked the dawn of a new era of human biology and medicine. Although these remarkable scientific advances improve the understanding of human biology, the question remains how this rap ... Full text Link to item Cite

Understanding specificity and sensitivity of T-cell recognition.

Journal Article Trends Immunol · December 2005 The response of T cells to antigen shows an amazing degree of both sensitivity and specificity, with a cell responding to 1-10 peptide-MHC complexes and being sensitive to single amino acid substitutions. Kinetic proofreading or feedback pathways achieve s ... Full text Link to item Cite

The impact of multiple T cell - APC encounters and the role of anergy

Journal Article Journal of Computational and Applied Mathematics · December 1, 2005 The activation of a T cell is a stochastic process, and depends on the integrated strength of signals 1 and 2 resulting from its encounter with an antigen presenting cell. The net outcome of thymic selection and peripheral circulation over many such encoun ... Full text Cite

16 Modelling T cell activation, proliferation, and homeostasis

Journal Article Studies in Multidisciplinarity · December 1, 2005 Full text Cite

Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression.

Journal Article Blood · November 1, 2005 Featured Publication Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complexes (MHCs) and costimulatory signals provided by antigen-presenting cells (APCs). It has been shown that T-cell activation without costimulation can lead to aner ... Full text Link to item Cite

Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells.

Journal Article J Immunol · June 15, 2005 Featured Publication Dendritic cells (DCs) are central to T cell immunity, and many strategies have been used to manipulate DCs to modify immune responses. We investigated the effects of antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) on DC phenotype and fu ... Full text Link to item Cite

Feedback control of T-cell receptor activation.

Journal Article Proc Biol Sci · May 7, 2004 Featured Publication The specificity and sensitivity of T-cell recognition is vital to the immune response. Ligand engagement with the T-cell receptor (TCR) results in the activation of a complex sequence of signalling events, both on the cell membrane and intracellularly. Fee ... Full text Link to item Cite

Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells.

Journal Article Atherosclerosis · April 2004 Featured Publication The vascular endothelial cell (EC) plays an essential role in the pathogenesis of inflammation, transplant rejection and tumour metastasis. Most research on vascular ECs uses human umbilical vein endothelial cells (HUVECs). However, HUVECs are derived from ... Full text Link to item Cite

Tolerance mechanisms and recent progress.

Journal Article Transplant Proc · March 2004 Featured Publication There has been tremendous progress in our understanding of the mechanisms mediating allograft tolerance, which have been revealed to be far more complex and regulated than hitherto suspected. New results have enriched our understanding of the relative cont ... Full text Link to item Cite

T cell sensitivity and specificity - Kinetic proofreading revisited

Journal Article Discrete and Continuous Dynamical Systems - Series B · January 1, 2003 T cells recognise foreign antigen presented by antigen presenting cells at extremely low concentrations, and are able to discriminate between different ligands with high specificity. McKeithan's kinetic proofreading model is often invoked to explain this s ... Full text Cite

An approach to modelling in immunology.

Journal Article Brief Bioinform · September 2001 Like most other fields in biology, immunology has been revolutionised by the techniques of molecular biology and the resulting explosion in available experimental data. It is argued that efforts to integrate the data to gain insight into how various subsys ... Full text Link to item Cite

Cooperative enhancement of specificity in a lattice of T cell receptors.

Journal Article Proc Natl Acad Sci U S A · May 8, 2001 Featured Publication Two of the most important models to account for the specificity and sensitivity of the T cell receptor (TCR) are the kinetic proofreading and serial ligation models. However, although kinetic proofreading provides a means for individual TCRs to measure acc ... Full text Link to item Cite

Analysis of cytokine dynamics in corneal allograft rejection.

Journal Article Proc Biol Sci · November 7, 1999 Featured Publication Motivated by the discovery of oscillations in tumour necrosis factor-alpha (TNF-alpha) concentration in the aqueous humour of rabbits undergoing corneal allograft rejection, a simple mathematical model is developed for the regulation of TNF-alpha, which in ... Full text Link to item Cite