Oxidative Medicine and Cellular Longevity

Research Article

MUTYH Actively Contributes to Microglial Activation and Impaired Neurogenesis in the Pathogenesis of Alzheimer’s Disease

Table 4

Functional annotation clustering of genes whose expression was significantly altered by MUTYH deficiency in the App^{NL-G-F/NL-G-F} hippocampus.


Category	Term	Number of genes^a	% of genes	Fold enrichment	value^b	Genes	Up^c	Down^d

Annotation cluster 1 (enrichment score: 2.16)
UP_KEYWORDS	Lysosome	6	5.83	5.58		*Npc2, Psap, Cd68, Ctsd, Rnaset2b, Rnaset2a*	0	6
GOTERM_CC_DIRECT	GO:0005764 lysosome	7	6.80	4.47		*Npc2, Psap, Gpc3, Cd68, Ctsd, Rnaset2b, Rnaset2a*	0	7
KEGG_PATHWAY	mmu04142 lysosome	4	3.88	7.20		*Npc2, Psap, Cd68, Ctsd*	0	4

Annotation cluster 2 (enrichment score: 1.71)
UP_KEYWORDS	Secreted	17	16.50	2.33		*Lyz2, Trem2, Serpina3n, Cst7, Spata6, Rnaset2b, Tnfsf13b, Rnaset2a, Ccl6, Npc2, Arsj, Smoc1, Psap, Gpc3, Ctsd, Gpha2, Havcr2*	3	14
UP_KEYWORDS	Glycoprotein	29	28.16	1.76		*Slc22a4, Ly6c2, Itgb5, Kcna4, Il6ra, Gpr83, Trem2, Cst7, Rnaset2b, Rnaset2a, Tnfsf13b, Foxred2, Grm2, Tmem145, Arsj, Psap, Gpc3, Chsy3, Gpha2, Ctsd, Prom2, Havcr2, Entpd1, Serpina3n, Krt18, Npc2, Smoc1, Plxnb2, Cd68*	9	20
GOTERM_CC_DIRECT	GO:0005576 extracellular region	16	15.53	1.93		*Lyz2, Il6ra, Trem2, Serpina3n, Cst7, Spata6, Tnfsf13b, Ccl6, Npc2, Arsj, Smoc1, Psap, Gpc3, Ctsd, Gpha2, Havcr2*	3	13
UP_KEYWORDS	Disulfide bond	22	21.36	1.63		*Ly6c2, Entpd1, Itgb5, Lyz2, Il6ra, Trem2, Gpr83, Cst7, Rnaset2b, Tnfsf13b, Rnaset2a, Grm2, Ccl6, Npc2, Smoc1, Psap, Cdk2ap1, Plxnb2, Cd68, Ctsd, Gpha2, Havcr2*	4	18
UP_SEQ_FEATURE	Signal peptide	24	23.30	1.52		*Ly6c2, Itgb5, Lyz2, Il6ra, Trem2, Gpr83, Serpina3n, Cst7, Spata6, Rnaset2b, Rnaset2a, Foxred2, Grm2, Ccl6, Npc2, Arsj, Smoc1, Psap, Gpc3, Cd68, Ctsd, Gpha2, Prom2, Havcr2*	6	18
UP_KEYWORDS	Signal	28	27.18	1.43		*Ly6c2, Itgb5, Lyz2, Il6ra, Gpr83, Trem2, Cst7, Spata6, Rnaset2b, Rnaset2a, Foxred2, Grm2, Tmem145, Ccl6, Arsj, Psap, Gpc3, Gpha2, Ctsd, Prom2, Havcr2, Serpina3n, Npc2, Smoc1, Pcdhb6, Plxnb2, Mxra7, Cd68*	7	21
UP_SEQ_FEATURE	Glycosylation site: N-linked (GlcNAc…)	26	25.24	1.44		*Slc22a4, Itgb5, Kcna4, Il6ra, Gpr83, Trem2, Cst7, Rnaset2b, Rnaset2a, Tnfsf13b, Foxred2, Grm2, Tmem145, Arsj, Psap, Gpc3, Chsy3, Gpha2, Ctsd, Prom2, Havcr2, Entpd1, Serpina3n, Npc2, Smoc1, Cd68*	9	17
GOTERM_CC_DIRECT	GO:0005615 extracellular space	13	12.62	1.83		Entpd1, *Lyz2, Il6ra, Serpina3n, Akr1b3, Cst7, Rnaset2b, Tnfsf13b, Rnaset2a, Ccl6, Psap, Gpc3, Ctsd*	3	10

Annotation cluster 3 (enrichment score: 1.54)
INTERPRO	IPR011992 EF-hand-like domain	6	5.83	4.76		*Spef2, Cracr2b, Tnnc1, Smoc1, Lpcat2, Slc25a13*	0	6
UP_KEYWORDS	Calcium	10	9.71	2.80		Entpd1, Pcdhb2, Tpm4, *Anxa3, Tnnc1, Arsj, Smoc1, Lpcat2, Pcdhb6, Slc25a13*	5	5
UP_SEQ_FEATURE	Domain: EF-hand 2	5	4.85	5.72		*Cracr2b, Tnnc1, Smoc1, Lpcat2, Slc25a13*	0	5
UP_SEQ_FEATURE	Domain: EF-hand 1	5	4.85	5.69		*Cracr2b, Tnnc1, Smoc1, Lpcat2, Slc25a13*	0	5
UP_SEQ_FEATURE	Calcium-binding region: 2	4	3.88	6.95		*Tnnc1, Smoc1, Lpcat2, Slc25a13*	0	4
UP_SEQ_FEATURE	Calcium-binding region: 1	4	3.88	6.28		*Tnnc1, Smoc1, Lpcat2, Slc25a13*	0	4
GOTERM_MF_DIRECT	GO:0005509 calcium ion binding	8	7.77	2.56		*Cracr2b, Pcdhb2, Anxa3, Tnnc1, Smoc1, Lpcat2, Pcdhb6, Slc25a13*	2	6

^aAmong all transcript clusters (34,472), 1,164 clusters with row expression exhibit significantly different expression levels among wild-type, App^{NL-G-F/NL-G-F}, and App^{NL-G-F/NL-G-F}·Mutyh^-/- hippocampi (ANOVA with eBayes correction, -test ). Among these clusters, 138 exhibit significant difference between both wild-type vs. App^{NL-G-F/NL-G-F} and App^{NL-G-F/NL-G-F} vs. App^{NL-G-F/NL-G-F}·Mutyh^-/- samples. Out of 138 clusters, 103 genes were functionally annotated and clustered in DAVID with the default classification stringency (medium). Top 3 clusters with are shown. ^bThe enrichment value (EASE score) of each annotation term in a given group with modified Fisher’s exact test. Terms with are shown. ^cNumber of genes whose expression levels in App^{NL-G-F/NL-G-F}·Mutyh^-/- are significantly increased compared to App^{NL-G-F/NL-G-F} samples. ^dNumber of genes whose expression levels in App^{NL-G-F/NL-G-F}·Mutyh^-/-are significantly decreased compared to App^{NL-G-F/NL-G-F} samples.