Browsing by Author "Woods, Christopher"

Now showing 1 - 4 of 4

Restricted
Bayesian inference of the number of factors in gene-expression analysis: application to human virus challenge studies
(BMC BIOINFORMATICS, 2010-11-09) Chen, Bo; Chen, Minhua; Paisley, John; Zaas, Aimee; Woods, Christopher; Ginsburg, Geoffrey S; Hero, Alfred; Lucas, Joseph; Dunson, David; Carin, Lawrence
Open Access
Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.
(Res Sq, 2022-04-07) Giroux, Nicholas S; Ding, Shengli; McClain, Micah T; Burke, Thomas W; Petzold, Elizabeth; Chung, Hong A; Rivera, Grecia O; Wang, Ergang; Xi, Rui; Bose, Shree; Rotstein, Tomer; Nicholson, Bradly P; Chen, Tianyi; Henao, Ricardo; Sempowski, Gregory D; Denny, Thomas N; De Ussel, Maria Iglesias; Satterwhite, Lisa L; Ko, Emily R; Ginsburg, Geoffrey S; Kraft, Bryan D; Tsalik, Ephraim L; Shen, Xiling; Woods, Christopher
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 seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associate with mild or moderate symptoms are already robust and include severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.
Open Access
Exploring Predictive Effects of Epstein-Barr Virus DNA Levels on Nasopharyngeal Cancer Staging and Relapse
(2025-04-15) Shaw, Neha
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a distinct geographic distribution, particularly affecting populations in Southeast Asia. Plasma EBV DNA has emerged as a key biomarker for NPC, offering potential applications in disease burden assessment, treatment monitoring, and relapse prediction. However, the transition from EBNA-1 to BamHI-W targeted polymerase chain reaction (PCR) assays in clinical practice raises questions about assay comparability and prognostic significance. This retrospective cohort study examines the correlation between EBV DNA levels and clinical tumor-node-metastasis (TNM) staging and evaluates the predictive value of EBV DNA for relapse in a synthetic dataset, meaning anonymized, artificially constructed data modeled after real patient distributions, of 100 stage II NPC patients from the National Cancer Centre Singapore (NCCS). Patients were stratified based on EBV DNA assay type, EBNA-1 (pre-2016) or BamHI-W (post-2016), and analyzed using statistical methods including Spearman’s correlation, linear regression, Kaplan-Meier survival analysis, and Cox proportional hazards modeling. Results indicated no statistically significant correlation between EBV DNA levels and TNM staging for either assay, suggesting that EBV DNA may not directly reflect tumor burden. Similarly, no significant differences in relapse-free survival were observed between the two assay groups. However, male gender emerged as a significant predictor of relapse (HR = 11.885, p = 0.0369), aligning with prior research on sex-based differences in NPC progression. These findings contribute to the ongoing discussion on EBV DNA as a prognostic biomarker in NPC. While EBV DNA remains clinically valuable, its integration into patient risk stratification should consider demographic and molecular factors beyond assay selection. Future research should explore prospective validation in larger, multi-institutional cohorts and investigate complementary biomarkers to enhance NPC prognostication.
Open Access
Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique Burdens of Disease.
(Open forum infectious diseases, 2016-09) Katrak, Shereen; Park, Lawrence P; Woods, Christopher; Muir, Andrew; Hicks, Charles; Naggie, Susanna
Background. Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and the primary cause of liver transplantation in the United States, and coinfection with human immunodeficiency virus (HIV) increases the risk of comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV-coinfected patients are poorly understood. This study compared the rates of HCU and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans. Methods. Hepatitis C virus- and HIV-infected and HIV/HCV-coinfected veterans in care with the Department of Veterans Affairs (VA) from 1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified by HIV- and HCV-associated International Classification of Diseases, Ninth Revision codes from the clinical case registry. We assessed rates of HCU using emergency department (ED) visits, outpatient visits, and hospitalization and primary diagnoses associated with hospitalization. Independent risk factors associated with hospitalization were also examined. Results. Rates of outpatient and ED visits increased over the 11-year study period for all groups, with inpatient admission rates remaining stable. The HCU rates were consistently higher for the coinfected than other cohorts. The primary reason for hospital admission for all groups was psychiatric disease/substance use, accounting for 44% of all admissions. Nadir CD4 <350 cells/mm³ was associated with higher rates of hospitalization versus nadir CD4 >500 cells/mm³. Conclusions. As the current population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age, they will continue to place a substantial and increasing demand on the US healthcare system, particularly in their utilization of ED and outpatient services. These data suggest the need for an ongoing investment in mental health and primary care within the VA healthcare system.