Table 1.

Top commonly predicted upstream regulatory hubs at a distance of 1 for DEGs in GS1 and GS2.

Molecular entity	Molecular function	Gene	Predicted activitya	Correct/totalb	Prediction p-valuec	Distanced	Evidencee
IRF1	Transcription factor	IRF1	+	60/62* 17/17**	4.24E-16f 7.63E-06g	1	Yes59,60
STAT1	Transcription factor	STAT1	+	64/70* 15/16**	1.22E-13f 2.59E-04g	1	Yes118–122
RelA (p65 NF-kB subunit)	Transcription factor	RELA	+	59/78* 14/15**	3.21E-06f 4.88E-04g	1	Yes123–132
STAT2	Transcription factor	STAT2	+	23/24* 8/8**	1.49E-06f 3.91E-03g	1	Yes117,133–137
IRF3	Transcription factor	IRF3	+	19/22* 9/9**	4.28E-04f 1.95E-03g	1	Yes138–148

^aPredicted activity of the key hub by causal reasoning is denoted by – if the hub is inhibited, and denoted by + if the hub is activated.

^bCorrect/total network predictions show the number of genes in the dataset predicted correctly over the total number of genes in the causal reasoning network.

^cCalculation distance from the upstream regulatory key hubs and downstream genes.

For example, distances of 2 and 3 identify key hubs that are distant key hubs, while a distance of 1 identify closest one-step away transcriptional factors.

^dp-value of the predicted protein activity calculated using the polynomial test.

^eEvidence for an existing experimental link between the transcription factor and menstrual irregularity.

^fp-value of the predicted protein activity calculated using the polynomial test for GS1.

^gp-value of the predicted protein activity calculated using the polynomial test for GS2.

*For GS1.

**For GS2.