Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock.
We have conducted longitudinal studies focused on the expression profiles of signaling pathways and gene networks in children with septic shock. Genome-level expression profiles were generated from whole blood-derived RNA of children with septic shock (n=30) corresponding to day one and day three of septic shock, respectively. Based on sequential statistical and expression filters, day one and day three of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to controls (n=15). Venn analysis demonstrated 239 unique genes in the day one dataset, 598 unique genes in the day three dataset, and 1,906 genes common to both datasets. Functional analyses demonstrated time-dependent, differential regulation of genes involved in multiple signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biology were persistently downregulated on both day one and day three. Further analyses demonstrated large scale, persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock subjected to longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses.
Shanley
Thomas P
TP
C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, Michigan, USA.
Cvijanovich
Natalie
N
Lin
Richard
R
Allen
Geoffrey L
GL
Thomas
Neal J
NJ
Doctor
Allan
A
Kalyanaraman
Meena
M
Tofil
Nancy M
NM
Penfil
Scott
S
Monaco
Marie
M
Odoms
Kelli
K
Barnes
Michael
M
Sakthivel
Bhuvaneswari
B
Aronow
Bruce J
BJ
Wong
Hector R
HR
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016678:Genome; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D046228:Microarray Analysis; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D012772:Shock, Septic / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D012313:RNA