Gene expression profiling in sepsis: timing, tissue, and translational considerations

• Gene expression analysis has yielded insights into the pathophysiology of sepsis.
• Gene expression analysis in sepsis differs conceptually and pragmatically from cancer studies.
• Gene expression data must be “downsized” to be useful in the ICU.
• Rapid assays are needed to make gene expression useful in the ICU.

Sepsis is a complex inflammatory response to infection. Microarray-based gene expression studies of sepsis have illuminated the complex pathogen recognition and inflammatory signaling pathways that characterize sepsis. More recently, gene expression profiling has been used to identify diagnostic and prognostic gene signatures, as well as novel therapeutic targets. Studies in pediatric cohorts suggest that transcriptionally distinct subclasses might account for some of the heterogeneity seen in sepsis. Time series analyses have pointed to rapid and dynamic shifts in transcription patterns associated with various phases of sepsis. These findings highlight current challenges in sepsis knowledge translation, including the need to adapt complex and time-consuming whole-genome methods for use in the intensive care unit environment, where rapid diagnosis and treatment are essential.