Using systems biology to simplify complex disease: immune cartography.

Area of Science:

• Systems biology
• Host-pathogen interactions
• Transcriptional analysis

Background:

• Current sepsis diagnostics are slow and lack specificity.
• Need for rapid, accurate blood tests to identify infection and guide therapy.

Purpose of the Study:

• To develop and validate a systems biology approach for diagnosing sepsis using transcriptional activity of immune cells.
• To differentiate between infectious and sterile inflammation and identify causative pathogens.
• To monitor patient response to therapy and immune recovery.

Main Methods:

• Analysis of microarray (RNA) data from circulating immune cells in mouse models and human subjects.
• Systems analysis of transcriptional activity to identify host response patterns.
• Mapping gene expression changes in response to endotoxin and during sepsis.

Main Results:

• Accurate diagnosis of abdominal and pulmonary sepsis in mouse models.
• Differentiation between Gram-negative and Gram-positive pneumonia based on host response.
• Characterization of endotoxin response in human volunteers.
• Quantitative assessment of immune recovery in critically ill septic patients.

Conclusions:

• Systems analysis of immune cell gene expression (immune cartography) is a validated approach for sepsis diagnosis and pathogen identification.
• This method has the potential for rapid, inexpensive, and accurate blood diagnostics.
• Further clinical trials are needed to validate leukocyte RNA diagnostics (riboleukogram) for clinical utility.