Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.
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2024-01
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To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19.
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McClain, Micah T, Ilya Zhbannikov, Lisa L Satterwhite, Ricardo Henao, Nicholas S Giroux, Shengli Ding, Thomas W Burke, Ephraim L Tsalik, et al. (2024). Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection. iScience, 27(1). p. 108288. 10.1016/j.isci.2023.108288 Retrieved from https://hdl.handle.net/10161/31493.
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Scholars@Duke
Micah Thomas McClain
Lisa L Satterwhite
Molecular epidemiology of environmental exposures, pesticide exposure and Parkinson’s disease, Cyanobacterial harmful algal blooms and ALS, and creating climate change resilient rural communities.
IN THE NEWS
2024
2023
https://radx-up.org/grants/rapid-research-pilot/rp2-awardees/
2022
https://dataclimatehealth.duke.edu/teams/
2015
https://www.jyi.org/2015-february/2015/2/1/a-day-on-the-farm-lisa-satterwhites-research-profile
Nicholas Giroux
Ephraim Tsalik
My research at Duke has focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease. This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance.
With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation what the underlying cause of illness is. For example, acute respiratory illness is among the most frequent reasons for patients to seek care. These symptoms, such as cough, sore throat, and fever may be due to a bacterial infection, viral infection, both, or a non-infectious condition such as asthma or allergies. Given the difficulties in making the diagnosis, most patients are inappropriately given antibacterials. However, each of these etiologies (bacteria, virus, or something else entirely) leaves a fingerprint embedded in the host’s response. We are very interested in finding those fingerprints and exploiting them to generate new approaches to understand, diagnose, and manage disease.
These principles also apply to sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Just as with acute respiratory illness, it is often difficult to identify whether infection is responsible for a patient’s critical illness. We have embarked on a number of research programs that aim to better identify sepsis; define sepsis subtypes that can be used to guide future clinical research; and to better predict sepsis outcomes. These efforts have focused on many systems biology modalities including transcriptomics, miRNA, metabolomics, and proteomics. Consequently, our Data Science team has utilized these highly complex data to develop new statistical methods, furthering both the clinical and statistical research communities.
These examples are just a small sampling of the breadth of research Dr. Tsalik and his colleagues have conducted.
In April 2022, Dr. Tsalik has joined Danaher Diagnostics as the VP and Chief Scientific Officer for Infectious Disease, where he is applying this experience in biomarkers and diagnostics to shape the future of diagnostics in ID.
Xiling Shen
Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).
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