Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis

Table 2 Ten proteins with the highest significance in multifactorial linear regression (constituting AGS) and presence of a link to the respective hallmark gene sets for pre-symptomatic individuals, RA patients, and controls compared two-by-two

Pre-symptomatic individuals vs. controls
Protein	Up- or downregulated^a	Adipogenesis		Interferon alpha response
		3.74E−09^#	0.0439^#	2.08E−07^#	0.0371^#
TNF	↑	+		+
PRR16	↑
CSF2	↑	+		+
CCDC85C	↑
CASP8	↑	+		+
IL33^†	↑			+
FAM81A	↑	+
SELE	↑	+		+
HTRA1	↑	+		+
MMP10	↑	+
Patients vs. Controls
Protein	Up- or downregulated^a	Adipogenesis		Heme metabolism
		2.57E−13^#	0.0058^#	1.77E−10^#	0.0022^#
TNF	↑	+		+
PRR16	↑
S100A12	↑	+		+
CSF2	↑	+		+
CASP8	↑	+		+
FAM81A	↑	+		+
MMP10	↑	+		+
HTRA1	↑	+		+
SELE	↑	+		+
ORM1, ORM2^†	↑	+		+
Pre-symptomatic individuals vs. patients
Protein	Up- or downregulated^b	Apical junction		Epithelial-mesenchymal transition		TGF-β signaling
		8.31E−13^#	0.0391^#	9.93E−43^#	0.0287^#	1.44E−09^#	0.0279^#
KCNB2^†	↓	+
S100A12	↑	+		+
EPB41L5^†	↑	+		+		+
COL6A1	↓	+		+		+
ZNF618^†	↑					+
S100A12	↑	+		+
TGFB3^†	↓	+		+		+
CCDC85C	↑	+				+
CSF2	↑	+		+		+
DSC3^†	↑	+		+		+
SLC11A1^†	↑

#Numbers below each hallmark title display enrichment p values: general NEA (left) and differential (right)
An expression change-based comparison in ^apre-symptomatic individuals or RA patients vs. controls and ^bRA patients vs. pre-symptomatic individuals
CASP8 caspase 8; CCDC85C coiled-coil domain containing 85C; COL6A1 collagen type VI alpha 1 chain; CSF2 colony-stimulating factor 2; DSC3 desmocollin 3; EPB41L5 erythrocyte membrane protein band 4.1 like 5; FAM81A family with sequence similarity 81 member A; HTRA1 HtrA serine peptidase 1; IL33 interleukin 33; KCNB2 potassium voltage-gated channel subfamily B member 2; MMP10 matrix metallopeptidase 10; ORM1, ORM2 orosomucoid 1,orosomucoid 2; PRR16 proline rich 16; S100A12 S100 calcium-binding protein A12; SELE selectin E; SLC11A1 solute carrier family 11 member 1; TGFB3 transforming growth factor beta 3; TNF tumor necrosis factor; ZNF618 zinc finger protein 618
^†Protein included uniquely in one of three top ten protein lists

ISSN: 1478-6362