Table 1.

Effect of EPCR expression on candidate upstream effectors in CD11c spleen cells predicted by IPA analysis of 3038 genes differentially expressed in spleen CD11c cells of EPCR^LOW mice

Upstream regulator	Activation Z-score	Activation state	P value of overlap	Target molecule ratio
Interferon γ	8.067	Activated	3.06 × 10−20	144/201
LPS	10.817	Activated	2.59 × 10−16	176/232
TLR4	5.245	Activated	4.07 × 10−9	32/55
TLR3	5.356	Activated	8.97 × 10−9	30/45
IRF7	5.444	Activated	6.97 × 10−8	31/33
Poly r(I:C)	6.915	Activated	1.44 × 10−7	58/66
IRF3	3.86	Activated	1.93 × 10−7	23/32
TICAM1	4.98	Activated	6.22 × 10−5	26/26
IRF8	2.98	Activated	4.91 × 10−4	16/28

Candidate pathways altered by diminished EPCR expression were analyzed with the Upstream Regulator tool of the IPA software package. This tool employs statistical algorithms that measure how the observed changes in gene expression overlap with the experimentally observed effects of putative regulators, as curated from the literature. Pathways controlled by the indicated upstream regulators are predicted to be more highly activated in wild-type mice as compared with EPCR-deficient mice. The overlap P value measures enrichment of genes in the dataset that are known to be regulated by a regulator R without taking into account the direction of regulation. The activation Z-score predicts the potential activity of a given regulator by using experimental information about the direction of regulation of affected genes by the regulator. The target molecule ratio is the number of molecules in the tested dataset, divided by the total number of molecules in the Ingenuity Knowledge database that make up that pathway.

Poly r(I:C), polyriboinosinic:polycytidylic acid.