Table 6.

The top-AID/APOBEC signature-linked Functional Annotations identified by systems biology approach (algorithm II; overlap with 4 individual target genes)

Functional Annotations-top-output_mixed_and_4_individual
Pos.	Functional Annotations	Mixed		APOBEC3G	ESR1	ID2	ID3	PTPRC (CD45)
		P-value	Molecules	Molecules	Molecules	Molecules	Molecules	Molecules
1	arthritis	1.53E-17	AIF1, ALOX5, AR, BGN, C3AR1, CASP1, CCL5, CCR5, CD86, CDH11, CDKN1A, CIITA, COL6A1, CSF2RB, CTSS, FAS, FCER1G, FCGRT, FN1, FSTL1, GBP2, GZMA, HCK, HLA-DOA, HLA-DPA1, HLA-DPB1, IGFBP4, IGFBP7, IL10RA, IL15, IRF1, ITGAM, ITPR1, JAM3, LST1, MS4A6A, PSMB9, PTPRC, SAMD9L, SDC2, SNAI2, SPOCK1, TAGAP, TIMP1, TLR3, TNFSF13B, ZFP36	ALOX5, CASP1, CCL5, CIITA, CTSS, GBP2, HLA-DOA, HLA-DPA1, HLA-DPB1, IL15, IRF1, ITGAM, MS4A6A, PSMB9, SAMD9L, TAGAP, TLR3, TNFSF13B		CDH11, CDKN1A, COL6A1, FAS, FCGRT, IGFBP4, IGFBP7, SDC2, SNAI2, TIMP1, ZFP36	BGN, CDH11, FN1, IGFBP4, ITPR1, JAM3, SDC2, SNAI2, SPOCK1	AIF1, C3AR1, CCL5, CCR5, CD86, CSF2RB, FCER1G, GZMA, HCK, IL10RA, LST1, MS4A6A, PTPRC
2	cell death of immune cells	8.52E-15	CASP1, CCL5, CCR5, CD2, CD47, CD86, CDKN1A, CIITA, COL1A1, CSF2RB, CYBB, EGFR, ESR1, EYA2, FAS, FCER1G, FN1, GIMAP4, GZMA, HCK, ID2, ID3, IFIH1, IL15, IRF1, ITGAM, ITPR1, LAIR1, LRIG1, MEIS1, PTPRC, SNAI2, TIMP1, TLR3, TNFSF13B	CASP1, CCL5, CIITA, IFIH1, IL15, IRF1, ITGAM, TLR3, TNFSF13B	CD47, ESR1, EYA2, LRIG1, MEIS1	CDKN1A, COL1A1, EGFR, FAS, ID2, ID3, SNAI2		CCL5, CCR5, CD2, CD86, CSF2RB, CYBB, FCER1G, GIMAP4, GZMA, LAIR1, PTPRC
3	rheumatoid arthritis	2.2E-13	AIF1, ALOX5, BGN, C3AR1, CCL5, CCR5, CD86, CDH11, CIITA, CSF2RB, FCGRT, GBP2, GZMA, HCK, HLA-DOA, HLA-DPA1, HLA-DPB1, IGFBP4, IGFBP7, IL10RA, ITPR1, JAM3, LST1, MS4A6A, PSMB9, PTPRC, SAMD9L, SDC2, SNAI2, SPOCK1, TAGAP, TIMP1, TLR3, TNFSF13B, ZFP36	ALOX5, CCL5, CIITA, GBP2, HLA-DOA, HLA-DPA1, HLA-DPB1, MS4A6A, PSMB9, SAMD9L, TAGAP, TLR3, TNFSF13B		CDH11, FCGRT, IGFBP4, IGFBP7, SDC2, SNAI2, TIMP1, ZFP36	BGN, CDH11, IGFBP4, ITPR1, JAM3, SDC2, SNAI2, SPOCK1	AIF1, C3AR1, CCL5, CCR5, CD86, CSF2RB, GZMA, HCK, IL10RA, LST1, MS4A6A, PTPRC
4	apoptosis	2.9E-12	AIF1, ALOX5, ANTXR2, APOL6, AR, ARMC10, BGN, CASP1, CCL5, CCR5, CD2, CD47, CD48, CD53, CDH11, CDKN1A, CIITA, COL1A1, CSF2RB, CTGF, CTSS, CYBB, DKK3, DLC1, EGFR, ENG, ESR1, EVA1C, EYA2, FAS, FBN1, FCER1G, FN1, FOXP1, FSTL1, GIMAP4, GZMA, HCK, HEXB, ID1, ID2, ID3, IFIH1, IGFBP4, IGFBP7, IL15, IRF1, ITGAM, ITPR1, LAIR1, LRIG1, MNDA, MUC16, PMEPA1, PMP22, PTPRC, RHOB, SDC2, SGPP1, SNAI2, SOX17, SPOCK1, SULF2, TIMP1, TLR3, TNFRSF14, TNFSF13B, VCAN, XAF1, ZFP36	ALOX5, APOL6, CASP1, CCL5, CIITA, CTSS, EVA1C, IFIH1, IL15, IRF1, ITGAM, TLR3, TNFSF13B, XAF1		ANTXR2, CDKN1A, COL1A1, CTGF, DLC1, EGFR, ENG, FAS, FOXP1, HEXB, ID1, ID2, ID3, IGFBP4, IGFBP7, RHOB, SDC2, SGPP1, SNAI2, SULF2, TIMP1, ZFP36	BGN, DKK3, DLC1, FBN1, FN1, FSTL1, ID1, ID2, ID3, IGFBP4, ITPR1, PMEPA1, PMP22, RHOB, SDC2, SNAI2, SPOCK1, SULF2	CCL5, CCR5, CD2, CD48, CD53, CSF2RB, CYBB, FCER1G, GZMA, HCK, LAIR1, MNDA, PTPRC
5	necrosis	1.36E-11	ALOX5, ANTXR2, AR, ARMC10, BGN, CASP1, CCL5, CCR5, CD2, CD47, CD48, CD86, CDH11, CDKN1A, CIITA, COL1A1, COL6A1, CSF2RB, CTGF, CTSS, CYBB, DKK3, DPYD, EGFR, ENG, ESR1, EVA1C, EYA2, FAS, FCER1G, FN1, FSTL1, GIMAP4, GZMA, HCK, =ID1, ID2, ID3, IFIH1, IGFBP4, IGFBP7, IL15, IRF1, ITGAM, ITPR1, LAIR1, LRIG1, MEIS1, MUC16, PMEPA1, PMP22, PTPRC, RHOB, ROCK2, SDC2, SGPP1, SNAI2, SOX17, SPOCK1, SULF2, TIMP1, TLR3, TNFRSF14, TNFSF13B, VCAN, XAF1	ALOX5, CASP1, CCL5, CIITA, CTSS, DPYD, EVA1C, IFIH1, IL15, IRF1, ITGAM, TLR3, TNFRSF14, TNFSF13B, XAF1		ANTXR2, CDKN1A, COL1A1, COL6A1, CTGF, EGFR, ENG, FAS, ID1, ID2, ID3, IGFBP4, IGFBP7, RHOB, ROCK2, SDC2, SGPP1, SNAI2, SULF2, TIMP1	BGN, DKK3, FN1, FSTL1, ID1, ID2, ID3, IGFBP4, ITPR1, PMEPA1, PMP22, RHOB, SDC2, SNAI2, SPOCK1, SULF2	CCL5, CCR5, CD2, CD48, CD86, CSF2RB, CYBB, FCER1G, GIMAP4, GZMA, HCK, LAIR1, PTPRC

IPA nomenclature was used for Functional Annotations. Since analysis for the 10-top-output_mixed_and_5 individual revealed only one functional annotation, the results of the top-output_mixed_and_4 individual are additionally shown. The ranking is based on the corresponding IPA-based p-value of the output_mixed; the molecules mapped to the Functional Annotation are listed