Understanding disease mechanisms with models of signaling pathway activities

BMC Systems Biology

Table 1 Analysis of the activity of the pathways by means of different approaches in the case-control comparison of early onset colorectal cancer

	Circuits			SEA
PATHWAY	Total	Case	Control	UP vs DOWN	UP vs ALL	DOWN vs ALL	GSEA	SPIA
PPAR SIGNALING PATHWAY	106	3	19	DOWN	ALL	ALL	DOWN*	INH*
ERBB SIGNALING PATHWAY	139	11	2	UP	UP	DOWN	DOWN*	INH
CALCIUM SIGNALING PATHWAY	20	2	2	DOWN	UP	DOWN	UP*	ACT
NEUROACTIVE LIGAND-RECEPTOR INTERACTION	7	0	0	UP	UP	ALL	UP*	ACT
APOPTOSIS	28	0	0	DOWN	ALL	DOWN	DOWN*	INH
WNT SIGNALING PATHWAY	37	6	6	UP	UP	DOWN	DOWN*	INH
NOTCH SIGNALING PATHWAY	14	0	0	DOWN	ALL	ALL	DOWN	INH
VEGF SIGNALING PATHWAY	10	2	0	DOWN	ALL	ALL	DOWN	INH
CELL ADHESION MOLECULES	43	6	3	UP	UP	ALL	UP*	- ¹
GAP JUNCTION	17	4	0	UP	UP	ALL	UP*	ACT
ANTIGEN PROCESSING AND PRESENTATION	6	0	0	DOWN	ALL	DOWN	UP	ACT
TOLL-LIKE RECEPTOR SIGNALING PATHWAY	103	0	0	UP	UP	DOWN	UP*	INH
JAK-STAT SIGNALING PATHWAY	7	7	0	DOWN	ALL	DOWN	UP*	INH
B CELL RECEPTOR SIGNALING PATHWAY	10	0	0	UP	UP	ALL	UP*	INH
Fc EPSILON RI SIGNALING PATHWAY	7	0	0	UP	ALL	ALL	DOWN*	INH
INSULIN SIGNALING PATHWAY	54	1	0	DOWN	UP	ALL	DOWN*	INH
GnRH SIGNALING PATHWAY	9	0	0	UP	UP	ALL	DOWN*	ACT
MELANOGENESIS	8	1	0	UP	ALL	ALL	UP	ACT
ADIPOCYTOKINE SIGNALING PATHWAY	31	0	2	DOWN	ALL	ALL	UP	INH

1 - This pathway is not implemented in SPIA.
The first column contains the name of the pathway. The next three columns, collectively labeled as circuits, list the number of sub-pathways in the pathways (Total) and the number of them significantly activated in cases with respect to controls (Case) or vice versa (Control) in the comparison, respectively. The three next columns, collectively labeled as SEA, list the results of a conventional functional enrichment test [3] in three situations: UP vs DOWN) when the significantly upregulated genes are compared to the significantly downregulated genes, UP vs ALL) when significantly upregulated genes are compared to rest of genes, and DOWN vs ALL) when significantly downregulated genes are compared to the rest of genes. UP, DOWN and ALL means where the major part of the pathway lies in the comparison. Significantly up- and downregulated genes are obtained by a conventional t-test with multiple test adjustment as implemented in the Babelomics program [89]. Although the trends of the results are coincident with the other analyses, none of them resulted significant. The column labeled GSEA contains a version of GSEA test [15] implemented in the Babelomics program. The * and the boldface indicate the trend is significant according to the test. The last column, labeled as SPIA, contains the result of the application of the pathway impact analysis [23].

ISSN: 1752-0509