TABLE 4.

CRE hypotheses of SPTLC123 or DEGS1 knockdown cells

Rank	CRE Hypothesis	Direction	Function	Enrichment	Correctness	C	I	A	T
SPTLC123 siRNA
1	Response to hypoxia	−	Response to O2	4.0e−21	<0.001	87	59	0	146
2	Methylprednisolone	+	Inflammation	3.4e−11	0.019	32	15	0	57
3	EPAS1	−	Response to O2	1.2e−09	<0.001	26	12	0	38
4	STAT4	−	Inflammation	6.9e−04	<0.001	17	5	0	22
7	Lipopolysaccharide	−	Inflammation	8.9e−06	<0.001	52	41	0	99
11	RELA	−	Inflammation	5.4e−06	0.002	17	8	0	26
12	Hypoxia	−	Response to O2	3.8e−04	<0.001	16	7	0	23
13	IL6	−	Inflammation	5.3e−08	<0.001	31	22	0	54
19	STAT3	−	Inflammation	4.0e−06	<0.001	22	14	0	36
20	HNF4A	−	Liver	8.5e−05	<0.001	17	9	0	26
DEGS1 siRNA
1	Response to hypoxia	−	Response to O2	1.0e−12	<0.001	85	52	0	137
2	Lipopolysaccharide	−	Inflammation	2.7e−06	<0.001	65	42	6	113
3	HNF1A	−	Liver	1.0e−09	<0.001	29	7	1	37
4	XBP1	−	ER stress	9.7e−10	<0.001	26	5	0	31
5	Response to oxidative  stress	−	Response to O2	3.0e−06	<0.001	29	8	0	37
6	PPARG	−	Adipocyte	1.7e−03	<0.001	26	8	2	36
7	HRAS	−	Cell cycle/ adhesion	1.9e−05	0.004	29	13	0	42
9	IL6	−	Inflammation	3.9e−06	<0.001	34	20	0	54
11	Bacterial infection	−	Inflammation	7.0e−06	<0.001	25	11	0	36
12	TGFB1	−	Cell cycle/ adhesion	2.5e−09	<0.001	52	39	6	97
13	ETS1	−	Cell cycle/ adhesion	6.9e−05	<0.001	22	9	0	31
17	EPAS1	−	Response to O2	3.5e−06	<0.001	23	11	0	34
18	HIF1A	−	Response to O2	2.5e−08	<0.001	31	20	2	53
19	NFE2L2	−	Response to O2	4.4e−06	<0.001	31	20	0	51
20	VHL	+	Response to O2	9.3e−06	<0.001	13	2	1	16

The top 20 most functionally relevant CRE hypotheses for each siRNA treatment were examined. The direction of the hypothesis is provided as a +, representing active/present, or a –, representing inactive/absent. Correctness and enrichment P values are computed as described in Materials and Methods. A single-letter column represents the statistically significant genes from the microarray gene expression profile for each treatment that is in the correct fold-change direction for the hypothesis (C), incorrect fold-change direction for the hypothesis (I), ambiguous fold-change based on the current literature for the hypothesis (A), and total genes for that hypothesis in the dataset (T). A complete hypotheses list for each targeted siRNA treatment and evidence matrix for the genes supporting these hypotheses can be found in supplementary File VI.