Using a large-scale knowledge database on reactions and regulations to propose key upstream regulators of various sets of molecules participating in cell metabolism

Table 4 PPARs and other regulatory partners were automatically proposed from experimental lists of PPARA gene targets

Input list 1^a		Input list 2^a		Input list 1^a		Input list 2^a
Score: coverage^b				Score: specificity^b
RXR				RXR
RXRA: PPARG	[4-29]^c	RXRA	[2-20]	RXRA: PXR-isoform1A	[1]	RXRA: PPARA	[4]
RXRA: PPARA	[4-29]	RXRA: VDR	[2-20]	RXR: VDR	[3]	RXRA: PPARD	[5-8]
RXRA: PPARD	[4-29]			RXRA: PPARD	[4]	RXRG: PPARA	[5-8]
RXRG: PPARA	[4-29]			RXRA: PPARG	[14]	RXRG: PPARD	[5-8]
RXRG: PPARD	[4-29]					RXRA: PPARG	[9,10]
RXRG: PPARG	[4-29]					RXRG: PPARG	[9,10]
RXRG: PPARG	[4-29]
VDR				VDR
VDR	[30-2223]	VDR	[2-20]	VDR: RXRA	[3]
VDR: RXRA	[30-2223]	VDR: RXRA	[2-20]
VDR: calcitriol	[30-2223]
VDR: calcitriol: 9-cis-retinoic acid: RXRA	[30-2223]
VDR: BLM	[30-2223]
PPARA				PPARA
PPARA: RXRA	[4-29]	PPARA	[21-1702]	PPARA: RXRA	[2]	PPARA: RXRA	[4]
PPARA: RXRG	[4-29]	PPARA: RXRA	[21-1702]
PPARG				PPARG
PPARG: RXRA	[4-29]	PPARG: abietic acid	[21-1702]	PPARG: RXRA	[14]	PPARG: RXRA	[9,10]
PPARG: RXRG	[4-29]	PPARG: 15d-PGJ2	[21-1702]			PPARG: RXRG	[9,10]
		PPARG: azPC	[21-1702]			PPARG	[12]
PPARD				PPARD
PPARD: RXRA	[4-29]	PPARD	[21-1702]	PPARD: RXRA	[4]	PPARD: RXR	[5-8]

^aDetailed lists are provided in Additional file1: Table S1, with i) list 1 including 250 regulated genes identified as controlled by PPARA from a literature review[20] and ii) list 2 including 136 differentially expressed genes in response to PPARA agonists in cell culture[21].
^bRegulatory candidates of these lists were elicited by an automatic algorithm based on encyclopedic information extracted from the TRANSPATH database and modeled as a causality graph. The candidates were scored for coverage (i.e., the number of targets regulated by a given candidate) or for specificity (i.e., a tradeoff between the number of regulated targets and the total number of regulated molecules) and the first 50^th candidates having the highest scores were retained.
^cThe range [N _i-N _j] indicated that the genes or the protein complex in which they participated had the same score as a set of N _j - N _i +1 molecules. When a molecule or a complex appeared more than once, only its best position was shown.

ISSN: 1752-0509