Table 1.
Summary of the public human genome-wide expression microarray datasets containing samples of adults, children, infants, and neonates with and without sepsis.
Fig 1.
Expression profiles of patients with sepsis from all age groups.
(A) Principle component analysis of the 4,535 genes whose expression differed with a coefficient of variance greater than 50% identified by unsupervised analysis. (B) Averaged arrays (f-test, 4,614 genes) with K-means clustering into five bins with mean centroid z-scores plotted for each bin and the number of genes in each bin. Error bars represent standard deviation. N-neonate, I-infant, C-children, A-adult.
Fig 2.
Canonical pathways analysis of 4,614 significant genes among septic adults, children, infants, and neonates.
(A) Septic neonates were the only group to show significant pathway alterations (TLR, TREM1, and iNOS signaling) as compared to all other groups. (B) Compared to children or infants, adults exhibited reduced expression of genes representing STAT3, EIF2, and thrombin signaling, but increased expression of genes representing the role of RIG1-like receptors in antiviral innate. (C) A comparison of children versus infants or neonates revealed increased expression of innate immune-related pathways in children including Fcγ receptor-mediated phagocytosis in macrophages and monocytes, as well as signaling pathways for IL-1, p38, cdc42, TLR, TREM1, and iNOS.
Fig 3.
The number of dysregulated genes in septic patients from baseline is proportional to age.
The number of significant (p<0.001) and differentially expressed (≥ 2-fold in either direction) genes for each age group and in each overlap between age groups. A cluster of 167 genes was identified in septic compared to healthy subjects regardless of age.
Fig 4.
Sample-level gene expression data for COCONUT-normalized pooled sepsis data.
Shown are the three genes with the greatest fold-change differences between age groups (top panel), along with three housekeeping genes (bottom panel). Top colored bars indicate age groupings; bottom bars (green and gold) show grouping of healthy and septic subjects within each age range. Within subgroups, subjects are further sorted by age. Data are shown in log2 scale. Exp-expression.