Gene expression signatures in blood from a West African sepsis cohort define host response phenotypes
Josh Chenoweth, Carlo Colantuoni, Deborah A. Striegel, Pavol Genzor, Joost Brandsma, Paul W. Blair, Subramaniam Krishnan, Elizabeth Chiyka, Mehran Fazli, Rittal Mehta, Michael Considine, Leslie Cope, Audrey C. Knight, Anissa N. Elayadi, Anne Fox, Ronna Hertzano, Andrew G. Letizia, Alex Owusu‐Ofori, Isaac Boakye, Albert A. Aduboffour, Daniel Ansong, Eno Akua Biney, George Oduro, Kevin L. Schully, Danielle V. Clark
Abstract
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.