Table 3.

Statistically enriched biological pathways reflected by the identified 13-component biomarker cluster based on the whole genome.

Pathway	# Biomarkers in cluster/Total # of biomarkers in pathway (Reactome)	p	pFDR-corrected a	Biomarkers
Inflammation pathways
Interleukin-4 and Interleukin-13 signaling	2/211	<0.001	<0.001	MMP3, MMP3
Neutrophil degranulation	4/480	<0.001	0.008	MMP9, CTSD, CSTB, PECAM1
Senescence-Associated Secretory Phenotype	1/91	0.005	0.038	IGFBP7
Extracellular matrix organization pathways
Degradation of the extracellular matrix	4/148	<0.001	0.001	MMP9, CTSD, MMP3, HSPG2
Extracellular matrix organization	5/301	<0.001	0.001	MMP9, CTSD, PECAM1, MMP3, HSPG2
Collagen degradation	3/64	<0.001	0.002	MMP9, CTSD, MMP3
Activation of Matrix Metalloproteinases	2/33	0.001	0.015	MMP9, MMP3
Assembly of collagen fibrils and other  multimeric structures	2/61	0.003	0.030	MMP9, MMP3
Collagen formation	2/90	0.007	0.036	MMP9, MMP3
Integrin cell surface interactions	2/85	0.006	0.036	PECAM1, HSPG2
Signal transduction pathways
ESR-mediated signaling	3/196	0.003	0.028	MMP9, CTSD, MMP3
Signaling by Interleukins	4/457	0.003	0.030	MMP9, MMP3
Signaling by Nuclear Receptors	3/273	0.006	0.036	MMP9, CTSD, MMP3
Extra-nuclear estrogen signaling	2/80	0.006	0.036	MMP9, MMP3
Transport of small molecules pathway
Intracellular oxygen transport	1/5	0.006	0.038	MB

^aFalse Discovery Rate-corrected p-values

The number of biomarkers involved in the cluster and belonging to the pathway are shown, as a ratio to the known total number of biomarkers involved in the pathway based on the Reactome pathway analysis tool. For example, 480 proteins are known to be involved in Neutrophil degranulation, of which four are part of our 13-component cluster (MMP9, CTSD, CSTB, PECAM1), this pathway is significantly enriched (p_{FDR-corrected} < 0.001).