Gene expression signatures in blood from a West African sepsis cohort define host response phenotypes.
Josh G ChenowethCarlo ColantuoniDeborah A StriegelPavol GenzorJoost BrandsmaPaul W BlairSubramaniam KrishnanElizabeth ChiykaMehran FazliRittal MehtaMichael ConsidineLeslie CopeAudrey C KnightAnissa ElayadiAnne FoxRonna HertzanoAndrew G LetiziaAlex Owusu-OforiIsaac BoakyeAlbert A AduboffourDaniel AnsongEno BineyGeorge OduroKevin L SchullyDanielle V ClarkPublished in: Nature communications (2024)
Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.
Keyphrases
- gene expression
- septic shock
- acute kidney injury
- intensive care unit
- clinical trial
- dna methylation
- sars cov
- randomized controlled trial
- single cell
- electronic health record
- immune response
- physical activity
- cross sectional
- bone marrow
- risk factors
- cancer therapy
- dendritic cells
- machine learning
- study protocol
- drug delivery
- skeletal muscle
- deep learning
- phase ii
- glycemic control