Development and Maturation of the Immune System in Preterm Neonates: Results from a Whole Genome Expression Study

Table 3

Summary of the pathway analysis for the differentially expressed genes between the groups. Pathways with FDR value less than 15% are shown.

Input to pathway analysis	Pathway name	FDR (%)
Genes presented a positive monotone trend on the 5th DOL, adjusted for multiple comparison 𝑃<0.01 (expression in extremely preterm is lower than that in very preterm; expression in very preterm is lower than that in moderately preterm)	T-cell receptor signaling pathway; Cell adhesion molecules (CAMs); Hematopoietic cell lineage; Intestinal immune network for IgA production	0.6; 1.3; 3.7; 12.5
Genes presented a negative monotone trend on the 5th DOL, adjusted for multiple comparison 𝑃<0.01	No pathway
Genes presented a positive monotone trend on the 28th DOL, adjusted for multiple comparison 𝑃<0.01	Primary immunodeficiency; T-cell receptor signaling pathway; Hematopoietic cell lineage; Intestinal immune network for IgA production; Cytokine-cytokine receptor interaction	0.01; 0.02; 1.3; 4.9; 10.5
Genes presented a negative monotone trend on the 28th DOL, adjusted for multiple comparison 𝑃<0.01	No pathway
Genes whose expressions were significantly higher on the 28th DOL compared to those on the 5th DOL (paired 𝑡-test, 𝑃<0.01; fold change > 1.5)	Graft-versus-host disease; Allograft rejection; Antigen processing and presentation; Intestinal immune network for IgA production; Cell adhesion molecules (CAMs); Primary immunodeficiency; Hematopoietic cell lineage; Natural killer cell-mediated cytotoxicity; Cytokine-cytokine receptor interaction; B-cell receptor signaling pathway; T-cell receptor signaling pathway; Jak-STAT signaling pathway	<0.001; <0.001; <0.001; <0.001; <0.001; 0.03; 0.04; 0.13; 0.5; 1.8; 5.8; 6.0
Genes whose expressions were significantly lower on the 28th DOL compared to those on the 5th DOL (paired 𝑡-test, 𝑃<0.01; fold change > 1.5)	Cell cycle; Regulation of actin cytoskeleton; Fc gamma R-mediated phagocytosis; Glycolysis/gluconeogenesis; Lysosome; Endocytosis; Base excision repair; Leukocyte transendothelial migration; Glutathione metabolism	0.27; 1.04; 1.09; 1.54; 3.46; 3.50; 5.69; 7.59; 8.30
Genes whose expressions were significantly higher in the group of extremely preterm infants (measurements on the 28th DOL) compared to those in the group of very preterm infants (measurements on the 5th DOL); 𝑃 values adjusted for multiple testing, 𝑃<0.01	Graft-versus-host disease; Cytokine-cytokine receptor interaction; Natural killer cell-mediated cytotoxicity	0.01; 0.4; 2.3
Genes whose expressions were significantly lower in the group of extremely preterm infants (measurements on the 28th DOL) compared to those in the group of very preterm infants (measurements on the 5th DOL); 𝑃 values adjusted for multiple testing, 𝑃<0.01	No pathway