Time-series gene expression profiles in AGS cells stimulated with Helicobacter pylori

Table 1 Number of different genes expressed at different time points compared with those of control AGS cells

Time point (h)	Up-regulation (n)	Down-regulation (n)	Total
0.5	109	209	318
1	140	242	382
2	151	203	354
4	126	291	417
6	198	156	354

P < 0.05, fold-change > 1.5, dataset2.

Table 2 Description of selected clustered genes from short time-series expression miner (STEM) using dataset2 as input

Cluster ID	Symbol
Profile 123	C4ORF18	USP47	CYP2J2	LGR5	FLRT3	LOC643031	TMEM117	CACHD1	C12ORF48	MTMR4
	RBL2	ZDHHC23	TTC13	NUFIP1	FLJ30596	AASDHPPT	C2ORF15	PGBD2	LRRC8D	EVI1
	SKP2	ZNF318	VPS13A	AMACR	ST6GAL1	AMD1	ELOVL6	PGM2	SLC35A5	CBR4
	EPB41L4B	C1ORF25	C1GALT1	ATG4C	MERTK	FANCL	LRIG3	RHPN1	PIP5K1B	SEMA3C
	P4HA1	LOC653094	SCAMP1	PPAP2B	MGC12965	UST	LRRC1	DEPDC1	DDC	ZNF278
	ITPR2	LOC653857	DIXDC1	KIAA1799	C17ORF58	TLR4	LOC645102	CDCA1	MINA	DNAJB14
	MRPL35	SLC25A20	ARRDC4	TRUB1	ARNTL	ZNF642	CASP8	TIGD2	SLC33A1	OTUD6B
	SPATA7	FBXO30	HSDL1	GLE1L	LOC642432	MGC33214	PRKCQ	DPY19L3	AKAP11	LOC653783
	SGOL2	PMS1	GABPA	TCF12	BMP4	KNTC2	BCKDHB	MANEA	GRHL3	ATP2C1
	HIF1A	PEX1	MTBP	ASF1A	SLC4A7	PDIK1L	C4ORF13	MAP3K1	MOBK1B	MRRF
	C7ORF25	MPHOSPH9	LOC159090	PTK9	B3GALT3	COG6	TMED7	TMEM19	LOC90693	FLJ12078
	RP11-311P8.3	ZNF181	COG8	KLHL23	RFC3	NBLA04196	LOC653101	TMTC4	TDP1	SCYL3
	PAQR3	TMTC3	BRD8	NFE2L3	PIGV	TSPAN12
Profile 3	PSG6	FGB	CEACAM1	CDKN1C	IFIT3	RSAD2	PSG7	FLJ11286	BTN3A2	STAT1
	FLJ20035
Profile 144	EHD2	RELB	COL16A1	GDF15	GNA15	LETM2	STX11	FOSL1	LOC647512	SQSTM1
	C12ORF59	ADM2	DDIT3	CHAC1	CSF2	DDIT4
Profile 12	ZC3HAV1	PSG9	LYZ	FGG	PSG2	PAGE4	REG4	GAD1	PPM1H	TMEM70
	LRP8	PAQR8	SH3BGRL	MYLIP	ROR1	C5ORF14	SUSD4	MGC3265	CADPS2	IDUA
	EPSTI1

Table 3 Statistically significant changed gene ontology of the four selected profiles

Profile	GO name	n	Corrected P value	Function code
111	Apical part of cell	2	0.00842	CC
71	Nucleic acid binding	12	2.7E-4	MF
	Zinc ion binding	23	0.00308	MF
	Regulation of transcription	22	0.01027	BP
	Myeloid cell differentiation	2	0.01577	BP
	Nucleus	39	2.9E-4	CC
	Intracellular	23	3.5E-4	CC
108	Small GTPase binding	2	0.01173	MF
	Oxido-reductase activity	6	0.02544	MF
	GPI anchor biosynthetic process	2	0.02591	BP
	Female pregnancy	3	0.02622	BP
	Golgi membrane	5	0.03987	CC
	Cell surface	3	0.03987	CC
83	DNA binding	6	0.00577	MF
	Metal binding	6	0.03346	MF
	Nucleus	10	0.01029	CC

Corrected P value < 0.05, derived from dataset1.

Table 4 Statistically significant changed gene ontology at each time point

Time point (h)	Up-regulation					Down-regulation
	GO ID	GO name	Genes	P value	Code	GO ID	GO name	Genes	P value	Code
0.5	GO:0008201	Heparin binding	5	7.1E-4	MF	GO:0006955	Immune response	20	0.00000	BP
	GO:0008134	Transcription factor binding	4	0.01585	MF	GO:0009615	Response to virus	10	0.00000	BP
	GO:0003700	Transcription activity	10	0.02835	MF	GO:0008150	Biological process	15	0.00896	BP
	GO:0008083	Growth factor activit	4	0.03882	MF	GO:0007267	Cell-cell signaling	10	0.00966	BP
	GO:0005576	Extracellular region	15	0.02875	CC	GO:0006935	Chemotaxis	6	0.01581	BP
	GO:0005634	Nucleus	28	0.03452	CC	GO:0006954	Inflammatory response	8	0.01581	BP
						GO:0008285	Negative regulation of cell proliferation	7	0.03430	BP
						GO:0007275	Multicellular organismal development	16	0.03576	BP
						GO:0008009	Chemokine activity	7	0.00000	MF
						GO:0046870	Cadmium ion binding	3	0.00194	MF
						GO:0016779	Nucleotidyl transferase activity	5	0.02486	MF
						GO:0005576	Extracellular region	37	0.00000	CC
						GO:0005615	Extracellular space	14	2.0E-4	CC
						GO:0005634	Nucleus	56	7.0E-4	CC
1	GO:0008201	Heparin binding	5	0.00265	MF	GO:0008009	Chemokine activity	6	3.5E-4	MF
	GO:0003700	Transcription factor activity	13	0.00886	MF	GO:0046870	Cadmium ion binding	3	0.00264	MF
	GO:0005515	Protein binding	38	0.01716	MF	GO:0003677	DNA binding	26	0.00264	MF
	GO:0045766	Positive regulation of angiogenesis	3	0.01125	BP	GO:0046872	Metal ion binding	36	0.01144	MF
	GO:0001558	Regulation of cell growth	6	0.01502	BP	GO:0008270	Zinc ion binding	34	0.02041	MF
	GO:0006915	Apoptosis	8	0.02591	BP	GO:0003674	Molecular function	15	0.02257	MF
	GO:0008285	Negative regulation of cell proliferation	6	0.02591	BP	GO:0003676	Nucleic acid binding	13	0.02257	MF
	GO:0005634	Nucleus	36	0.00597	CC	GO:0016779	Nucleotidyl transferase activity	4	0.02571	MF
	GO:0005575	Cellular component	10	0.02160	CC	GO:0005515	Protein binding	61	0.03204	MF
						GO:0003704	Specific RNA polymerase II transcription factor activity	3	0.04080	MF
						GO:0009615	Response to virus	10	0.00000	BP
						GO:0006955	Immune response	18	0.00000	BP
						GO:0006355	Regulation of transcription DNA-dependent	39	4.0E-5	BP
						GO:0006350	Transcription	31	4.5E-4	BP
						GO:0008150	Biological process	18	0.00348	BP
						GO:0007267	Cell-cell signaling	11	0.00480	BP
						GO:0006954	Inflammatory response	8	0.03385	BP
						GO:0045087	Innate immune response	5	0.04274	BP
						GO:0005634	Nucleus	71	0.00000	CC
						GO:0005576	Extracellular region	37	1.1E-4	CC
						GO:0005615	Extracellular space	13	0.00474	CC
						GO:0005622	Intracellular	31	0.01344	CC
						GO:0005575	Cellular component	15	0.03381	CC
2	GO:0003700	Transcription factor activity	18	1.4E-4	MF	GO:0009615	Response to virus	10	0.00000	BP
	GO:0008201	Heparin binding	5	0.00193	MF	GO:0006955	Immune response	16	0.00000	BP
	GO:0043565	Sequence-specific DNA binding	10	0.01819	MF	GO:0008150	Biological process	18	6.6E-4	BP
	GO:0008083	Growth factor activity	5	0.01885	MF	GO:0007267	Cell-cell signaling	10	0.01111	BP
	GO:0005178	Integrin binding	3	0.02722	MF	GO:0006954	Inflammatory response	8	0.01911	BP
	GO:0008134	Transcription factor binding	4	0.02722	MF	GO:0045087	Innate immune response	5	0.02866	BP
	GO:0008009	Chemokine activity	3	0.02849	MF	GO:0007565	Female pregnancy	5	0.03928	BP
	GO:0046872	Metal ion binding	23	0.04806	MF	GO:0005576	Extracellular region	36	1.0E-5	CC
	GO:0045944	Positive regulation of transcription from RNA polymerase II promoter	7	0.00234	BP	GO:0005615	Extracellular space	13	0.00113	CC
	GO:0006955	Immune response	10	0.00470	BP	GO:0005634	Nucleus	51	0.00899	CC
	GO:0008285	Negative regulation of cell proliferation	7	0.00681	BP	GO:0046870	Cadmium ion binding	3	0.01145	MF
	GO:0000122	Negative regulation of transcription from RNA polymerase II promoter	6	0.00681	BP	GO:0016831	Carboxy-lyase activity	3	0.02198	MF
	GO:0006915	Apoptosis	9	0.00713	BP	GO:0030674	Protein binding bridging	4	0.04373	MF
	GO:0006954	Inflammatory response	7	0.00769	BP
	GO:0001558	Regulation of cell growth	5	0.00914	BP
	GO:0009611	Response to wounding	3	0.01457	BP
	GO:0005615	Extracellular space	12	8E-5	CC
	GO:0005634	Nucleus	42	2.4E-4	CC
	GO:0005576	Extracellular region	22	4E-4	CC
	GO:0030173	Integral to Golgi membrane	3	0.02101	CC
4	GO:0008083	Growth factor activity	8	1.0E-5	MF	GO:0009615	Response to virus	12	0.00000	BP
	GO:0005125	Cytokine activity	6	3.7E-4	MF	GO:0007565	Female pregnancy	9	1.6E-4	BP
	GO:0046983	Protein dimerization activity	6	0.00123	MF	GO:0006955	Immune response	17	5.0E-4	BP
	GO:0005100	Rho GTPase activator activity	3	0.00268	MF	GO:0001525	Angiogenesis	7	0.02671	BP
	GO:0008201	Heparin binding	4	0.00826	MF	GO:0007267	Cell-cell signaling	10	0.02671	BP
	GO:0003700	Transcription factor activity	13	0.00826	MF	GO:0008150	Biological process	19	0.02928	BP
	GO:0008047	Enzyme activator activity	3	0.01045	MF	GO:0016477	Cell migration	5	0.03984	BP
	GO:0005178	Integrin binding	3	0.01447	MF	GO:0005576	Extracellular region	45	0.00000	CC
	GO:0016563	Transcription activator activity	4	0.02237	MF	GO:0005577	Fibrinogen complex	3	6.0E-4	CC
	GO:0005515	Protein binding	33	0.03960	MF	GO:0005615	Extracellular space	14	0.00843	CC
	GO:0043565	Sequence-specific DNA binding	8	0.03960	MF	GO:0031093	Platelet α granule lumen	4	0.01203	CC
	GO:0006955	Immune response	11	2.4E-4	BP	GO:0016020	Membrane	61	0.03962	CC
	GO:0006915	Apoptosis	9	0.00440	BP	GO:0005794	Golgi apparatus	15	0.03962	CC
	GO:0030183	B cell differentiation	3	0.01798	BP
	GO:0045944	Positive regulation of transcription from RNA polymerase II promoter	5	0.03323	BP
	GO:0000079	Regulation of cyclin-dependent protein kinase activity	3	0.03704	BP
	GO:0007050	Cell cycle arrest	4	0.03704	BP
	GO:0008284	Positive regulation of cell proliferation	5	0.03704	BP
	GO:0007267	Cell-cell signaling	6	0.03704	BP
	GO:0001558	Regulation of cell growth	5	0.0407	BP
6	GO:0005515	Protein binding	65	0.00000	MF	GO:0046870	Cadmium ion binding	3	0.00135	MF
	GO:0003700	Transcription factor activity	24	1.0E-5	MF	GO:0003674	Molecular function	13	0.00852	MF
	GO:0008083	Growth factor activity	8	3.5E-4	MF	GO:0008009	Chemokine activity	4	0.00852	MF
	GO:0003714	Transcription co-repressor activity	7	3.5E-4	MF	GO:0003950	NAD+ADP-ribosyl transferase activity	3	0.01169	MF
	GO:0005125	Cytokine activity	8	3.5E-4	MF	GO:0030674	Protein binding bridging	3	0.04041	MF
	GO:0005100	Rho GTPase activator activity	4	3.5E-4	MF	GO:0009615	Response to virus	12	0.00000	BP
	GO:0003700	Transcription factor activity	7	6.2E-4	MF	GO:0006955	Immune response	16	0.00000	BP
	GO:0046983	Protein dimerization activity	7	6.9E-4	MF	GO:0007565	Female pregnancy	9	0.00000	BP
	GO:0008270	Zinc ion binding	32	0.00504	MF	GO:0008150	Biological process	14	0.00612	BP
	GO:0046872	Metal ion binding	32	0.00827	MF	GO:0007267	Cell-cell signaling	8	0.00676	BP
	GO:0005085	Guanyl-nucleotide exchange factor activity	5	0.02023	MF	GO:0006952	Defense response	5	0.00728	BP
	GO:0043565	Sequence-specific DNA binding	11	0.03272	MF	GO:0030168	Platelet activation	3	0.01864	BP
	GO:0008201	Heparin binding	4	0.03502	MF	GO:0051258	Protein polymerization	3	0.03966	BP
	GO:0005178	Integrin binding	3	0.04652	MF	GO:0005576	Extracellular region	44	0.00000	CC
	GO:0006915	Apoptosis	13	0.00173	BP	GO:0005615	Extracellular space	13	6.0E-5	CC
	GO:0006950	Response to stress	7	0.00173	BP	GO:0005577	Fibrinogen complex	3	6.0E-5	CC
	GO:0007050	Cell cycle arrest	6	0.00788	BP	GO:0031093	Platelet α granule lumen	4	8.1E-4	CC
	GO:0045944	Positive regulation of transcription from RNA polymerase II promoter	7	0.01021	BP
	GO:0045740	Positive regulation of DNA replication	3	0.01720	BP
	GO:0008360	Regulation of cell shape	4	0.02121	BP
	GO:0008285	Negative regulation of cell proliferation	8	0.02486	BP
	GO:0000122	Negative regulation of transcription from RNA polymerase II promoter	7	0.02486	BP
	GO:0009611	Response to wounding	3	0.02698	BP
	GO:0030183	B cell differentiation	3	0.02698	BP
	GO:0007229	Integrin-mediated signaling pathway	5	0.02698	BP
	GO:0006954	Inflammatory response	7	0.02698	BP
	GO:0007179	Transforming growth factor β receptor signaling pathway	4	0.02698	BP
	GO:0043066	Negative regulation of apoptosis	4	0.02698	BP
	GO:0006935	Chemotaxis	5	0.04499	BP
	GO:0007010	Cytoskeleton organization and biogenesis	5	0.04841	BP
	GO:0006955	Immune response	10	0.04843	BP
	GO:0005576	Extra cellular region	31	9.0E-5	CC
	GO:0005615	Extra cellular space	14	6.6E-4	CC
	GO:0005622	Intracellular	29	0.00843	CC
	GO:0005737	Cytoplasm	40	0.03660	CC

ONTO-TOOLS/OE2GO was used to identify the differentially expressed GO terms based on the hypergeometric distribution and corrected P value (< 0.05). The GO identified number (GOID), GO term name (GO name), the number of genes changed within each functional gene category, P values are listed. GO terms with at least 3 genes changed and corrected P values < 0.05 are listed in Table 4.

Table 5 Top four significantly perturbed pathways at each time point

Time point	0.5 h	1 h	2 h	4 h	6 h
Gene mapping
Up-regulation	CAM	P53	MAPK	CAM	CAM
	MAPK	TGF	ECHP	CY-CY	CY-CY
	P53	MAPK	RCC	MAPK	JAK-STA
	TGF	CCC	P53	JAK-STA	MAPK
Down-regulation	APP	APP	APP	Phos	APP
	Toll	CY-CY	CY-CY	APP	CY-CY
	CY-CY	Toll	Toll	Toll	Toll
	NKMC	Mela	Mela	Mela	Mela