Table 1.

Summary of the results for human cell cycle data

	TM-1	TM-2	TM-3,4
TREMOR	• 41 significant TFs detected	• 98 TM-2s detected.	• 63 TM-3s detected.
	• 15 TFs have P-values lower than the lowest P-value in the randomly permuted set.	• 35 include E2F and 36 include NF-Y.	• All include NF-Y and 15 include E2F.
	• NF-Y is at rank 1, E2F at rank 2 and CREB at rank 12	• Rank-1 TM-2—(NF-Y c- Myc:Max). These TFs form a complex in cell cycle regulation.	• 158 TM-4s detected.
	• Of the remaining 12, 7 have evidence of potential cell cycle involvement: HOXA7 (34) (the reference shows evidence of involvement of a close relative, Hoxa-10), Elk-1 (35), ETF (36) (ETF regulates p53 which mediates cell cycle arrest), AR (37), AP-2alpha (38), Ik-2 (39), v-Myb[v-Myb motif enrichment in cell cycle gene promoters was previously shown in Ref. (40) and direct involvement in cell cycle was shown for a close relative c-Myb in Ref. (41)].	• Rank-3 TM-2—(NF-Y E2F).These TFs are are known to interact (42).	• Of these, 150 include NF-Y, and 71 include both E2F and NF-Y.
		• (NF-Y AP-2) has a P-value = 1.1E−14. CDP and AP-2 function synergistically to regulate H3.2 during cell cycle and NF-Y and CDP bind to neighboring CAAT boxes in H3.2 promoter (43).
OPOSSUM2	TM-2	TM-3
	• 20 significant (P ≤ 0.05) TM-2s.	oPOSSUM2 detected 33 size-3 TMs (64 by TREMOR). Surprisingly the
	• Only two include E2F, in combination with NF-Y and Gfi. Both combinations are detected by TREMOR.	three cell cycle regulators—E2F, NF-Y or CREB—were not included in any of the TMs returned by oPOSSUM2, while a majority of TREMOR TM-3s include these key TFs.
	• (CREB E2F) not detected.
	• Only two TM-2s include NF-Y.
	• In general, oPOSSUM detects fewer and more varied TMs while TREMOR TMs revolve around primary TFs- E2F, NF-Y and CREB.
CREME	• On our gene set, CREME yielded a total of two TM-3s—(AREB6, STAT4, TCF1P) and (SRY, STAT4, TCF1P, EGR). These do not include the three well-known cell cycle TFs—E2F, CREB and NFY.
	• CREME was applied to a slightly different cell cycle data in the original paper (19). CREME detected 47 TFs, compared to TREMOR's 41. CREME reports only seven significant non-redundant TMs. The three TM-2s are (ZF5 GR), (ZF5 HAND1E47) and (ZF5 USF2). The first two are detected by TREMOR. USF2 is an E-box TF and there are several TM-2s detected by TREMOR that link ZF5 with an E-box protein. The larger TMs detected by CREME were not detected by TREMOR.

For oPOSSUM2 and CREME, the results are compared to TREMOR. Unless otherwise specified, for TREMOR we only mention the TMs whose P-values were lower than the lowest P-value for the corresponding randomly permuted set (see text).