TY - JOUR
T1 - Using systems biology to simplify complex disease
T2 - Immune cartography
AU - Polpitiya, Ashoka D.
AU - McDunn, Jonathan E.
AU - Burykin, Anton
AU - Ghosh, Bijoy K.
AU - Cobb, J. Perren
N1 - Funding Information:
This work was supported, in part, by NIH R21GM075023, NIH U54GM62119, NIH T32GM08795, and the Barnes-Jewish Hospital Foundation Research Award. Dr. McDunn has received an honoraria from Pfizer, Inc. The remaining authors have not disclosed any potential conflicts of interest.
PY - 2009/1
Y1 - 2009/1
N2 - What if there was a rapid, inexpensive, and accurate blood diagnostic that could determine which patients were infected, identify the organism(s) responsible, and identify patients who were not responding to therapy? We hypothesized that systems analysis of the transcriptional activity of circulating immune effector cells could be used to identify conserved elements in the host response to systemic inflammation, and furthermore, to discriminate between sterile and infectious etiologies. We review herein a validated, systems biology approach demonstrating that 1) abdominal and pulmonary sepsis diagnoses can be made in mouse models using microarray (RNA) data from circulating blood, 2) blood microarray data can be used to differentiate between the host response to Gram-negative and Gram-positive pneumonia, 3) the endotoxin response of normal human volunteers can be mapped at the level of gene expression, and 4) a similar strategy can be used in the critically ill to follow septic patients and quantitatively determine immune recovery. These findings provide the foundation of immune cartography and demonstrate the potential of this approach for rapidly diagnosing sepsis and identifying pathogens. Further, our data suggest a new approach to determine how specific pathogens perturb the physiology of circulating leukocytes in a cell-specific manner. Large, prospective clinical trails are needed to validate the clinical utility of leukocyte RNA diagnostics (e.g., the riboleukogram).
AB - What if there was a rapid, inexpensive, and accurate blood diagnostic that could determine which patients were infected, identify the organism(s) responsible, and identify patients who were not responding to therapy? We hypothesized that systems analysis of the transcriptional activity of circulating immune effector cells could be used to identify conserved elements in the host response to systemic inflammation, and furthermore, to discriminate between sterile and infectious etiologies. We review herein a validated, systems biology approach demonstrating that 1) abdominal and pulmonary sepsis diagnoses can be made in mouse models using microarray (RNA) data from circulating blood, 2) blood microarray data can be used to differentiate between the host response to Gram-negative and Gram-positive pneumonia, 3) the endotoxin response of normal human volunteers can be mapped at the level of gene expression, and 4) a similar strategy can be used in the critically ill to follow septic patients and quantitatively determine immune recovery. These findings provide the foundation of immune cartography and demonstrate the potential of this approach for rapidly diagnosing sepsis and identifying pathogens. Further, our data suggest a new approach to determine how specific pathogens perturb the physiology of circulating leukocytes in a cell-specific manner. Large, prospective clinical trails are needed to validate the clinical utility of leukocyte RNA diagnostics (e.g., the riboleukogram).
KW - Critical care
KW - Diagnostics
KW - Genomics
KW - Interactome
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=58849095074&partnerID=8YFLogxK
U2 - 10.1097/CCM.0b013e3181920cb0
DO - 10.1097/CCM.0b013e3181920cb0
M3 - Article
C2 - 19104218
AN - SCOPUS:58849095074
VL - 37
SP - S16-S21
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - SUPPL. 1
ER -