Table S1.

Comparison of secondary structure modeling approaches

RNA name	Length, nt	No. of helices*	Fold		Fold + DMS†		Fold + M2‡		Fold + DMS† + M2‡		ShapeKnots		ShapeKnots + DMS†		ShapeKnots + M2‡		ShapeKnots + DMS† + M2‡		M2-net
			TP	FP	TP	FP	TP	FP	TP	FP	TP	FP	TP	FP	TP	FP	TP	FP	TP	FP
P4–P6 domain	160	8	8	1	8	1	7	1	8	1	8	1	8	1	7	1	8	1	7	0
GIR1 ribozyme	188	11	6	6	9	2	9	2	10	0	6	5	9	1	10	2	11	0	5	0
RNase P C domain	265	13	6	8	9	5	9	3	10	2	6	8	9	5	11	2	11	1	10	1
AdoCbl riboswitch	168	10	6	4	7	1	9	0	10	0	6	4	7	1	9	0	10	0	4	0
ydaO riboswitch	124	7	5	2	6	0	5	2	6	0	5	3	6	1	5	2	6	1	2	0
Zika xrRNA	71	5	4	1	4	1	3	2	3	2	4	1	5	0	3	2	4	1	2	0
TPP riboswitch	80	6	5	0	6	0	4	0	6	0	5	0	6	0	4	0	6	0	3	0
Total	1,056	60	40	22	49	10	46	10	53	5	40	22	50	9	49	9	56	4	33	1
False negative rate, %			33.3		18.3		23.3		11.7		33.3		16.7		18.3		6.7		45
False positive rate, %			35.5		16.9		17.9		8.6		35.5		15.3		15.5		6.7		2.9
Sensitivity, %			66.7		81.7		76.7		88.3		66.7		83.3		81.7		93.3		55
PPV, %			64.5		83.1		82.1		91.4		64.5		84.7		84.5		93.3		97.1

FP, false positives; PPV, positive predictive value; TP, true positives.

^*Helices with length greater than two Watson–Crick (or G•U wobble) base pairs.

^†Use of 1D DMS data to guide folding through energy bonuses (5).

^‡Use of Z-scores derived from 2D M2-seq experiments, applied as in ref. 16.