Table 5. The top six upstream regulators predicted by IPA to be activated in atretic versus healthy follicles.

Upstream Regulator	Activation z-Score†	P value of Overlap*	Target Molecules in Data Set
1-alpha, 25-dihydroxy vitamin D3	5.871	1.63E-31	ANGPT2, ANLN, BRCA1, BUB1B, CCNA2, CCNB1, CD14, CDC20, CDC6, CDCA5, CDCA8, CDK1, CDT1, CEBPD, CHAF1A, CHAF1B, CHTF18, ECT2, EGR1, ESPL1, EZH2, FEN1, FOS, GEM, H2AFZ, HPGD, IL10RA, IL6, JUN, KIAA0101, KIF20A, KIF22, KIF23, KPNA2, LIG1, LTF, MAD2L1, MCM2, MCM3, MCM4, MCM5, MELK, MRC1, NRM, NUPR1, NUSAP1, PCNA, POLE2, PRC1, RACGAP1, RAD51AP1, RBPMS, RPA2, RRM2, SLC7A7, SMC2, SPAG5, TCF19, TK1, TPX2, VEGFA
TP53	4.718	1.18E-30	A2M, ADCK3, ANLN, APOE, ASF1B, ASPM, ASS1, AURKA, AURKB, BIRC5, BRCA1, BUB1, BUB1B, C11orf82, C1QC, CCDC99, CCNA2, CCNB1, CCNB2, CCNE2, CDC20, CDC25C, CDC6, CDK1, CDT1, CENPF, CHEK1, CKAP2, CKS1B, CLU, CP, CSTB, CTSB, CTSF, CYB5R3, DCK, DSN1, DUT, E2F8, EGR1, ENPP2, ESPL1, EZH2, FANCI, FEN1, FOS, GPX3, H2AFX, H2AFZ, HJURP, HMGB2, HMMR, HMOX1, IL6, ITGB5, JUN, KCNMA1, KIAA0101, KIF23, KNTC1, KPNA2, LGALS3, MAD2L1, MCM2, MCM3, MCM4, MCM5, MCM6, MT1H, MYBL2, NCAPD3, NCAPG, NCAPH, NDC80, NDRG1, NOL3, NUPR1, NUSAP1, PCDH7, PCNA, PLK1, POLE2, PRC1, PRDM1, PSRC1, PTGDS, RACGAP1, RAD51AP1, RRAD, RRM1, RRM2, S100A2, SERPING1, SLC16A1, SMC2, SMC4, TGFBI, TOP2A, TPX2, TYMS, UBE2C, UHRF1, VEGFA, VRK1
let-7	5.452	1.35E-23	AURKA, AURKB, BRCA1, BUB1, BUB1B, CCNA2, CCNB1, CCNE2, CCNF, CDC20, CDC6, CDCA2, CDCA3, CDCA5, CDCA8, CDK1, CDT1, CHEK1, CKS1B, E2F8, EZH2, MAD2L1, MCM2, MCM3, MCM4, MCM5, MCM6, ORC1, RRM1, RRM2
RB1	3.133	1.23E-22	ANGPT2, ASF1B, AURKB, BIRC5, BRCA1, CCNA2, CCNB1, CCNE2, CDC25C, CDC6, CDCA5, CDK1, CDT1, CHAF1A, CITED2, DCK, EGR1, EZH2, FEN1, FOS, HMGB2, IL6, LIG1, MCM2, MCM3, MCM4, MCM5, MCM6, MELK, MYBL2, ORC1, PCNA, PLK1, RAD51AP1, RRM1, RRM2, TCF19, TYMS, VEGFA, VRK1
CDKN2A	4.513	2.20E-18	ASF1B, AURKB, BIRC5, CCNA2, CDC25C, CDCA5, CDK1, CHAF1A, CITED2, DCK, EGR1, EZH2, FEN1, GAS7, HMGB2, IL6, ITGB5, JUN, KIFC1, MCM4, MCM5, MELK, MYBL2, PCNA, PLK1, RAD51AP1, RRM1, RRM2, TCF19, TGIF1, TK1, VEGFA, VRK1
IKBKB	3.563	2.81E-17	ACP5, AURKB, BRCA1, CCNA2, CCNE2, CCR1, CDC6, CEBPD, CH25H, CKS1B, CLU, CP, CTSB, CTSF, CTSZ, CXCR4, ECT2, EGR1, ENPP2, EZH2, FOS, H2AFX, HMOX1, IL6, ITGB5, KIF20A, KIF23, LMNB1,MT1H, PCDH7, PLK1, SAA2, VCAM1, VEGFA

^†The predicted activation state is inferred from the bias-corrected z-score. The bias-corrected z-score is computed based on the proportion of target genes present in the data set which are directionally regulated as expected according to known effects of the regulator on the target compiled from the literature.

*The P value of overlap measures the statistical significance of overlap using Fisher's exact t-test, between genes from the data set and those known to be acted upon by an upstream regulator.