Separate values are computed for the single-domain targets, the two-domain targets and all targets.

Twelve CAFASP-DP methods have been evaluated along with InterProScan:

1. Adda
2. Armadillo
3. Biozon
4. Dompred-domssea
5. Dompred-dps
6. Dompro
7. Dopro
8. Globplot
9. InterProScan
10. Mateo
11. Ssep-Domain
12. Robetta-ginzu
13. Robetta-rosettadom

1. Absolute Number of Correctly Predicted Targets
In addition to the 12 domain prediction servers, three controls have been used: Control1, Control2 and Random. Control1 is computed by predicting all the targets as single-domain proteins and control2 is computed by predicting all the targets as two-domain proteins with a domain boundary at the centre of the sequence. The random control chooses between control1 and control2 at random. Finally, a consensus has been calculated based on a majority vote and some weighting scheme in case of a tie.

A prediction is considered as correct if the number of predicted domains is correct. For two-domain targets, the predicted domains should be continuous, i.e, with no split domains.

Methods	Number of targets predicted as single-domain	Number of targets predicted correctly as single-domain	Number of targets predicted as two-domain	Number of targets predicted correctly as two-domain	Number of targets predicted as multi-domain (number of domains >2) or split-domains	Missing Predictions
Control1	58	41	0	0	0	0
Control2	0	0	58	17	0	0
Random	30	21	28	8	0	0
ADDA	48	35	9	3	1	0
Armadillo	4	4	22	4	25	7
Biozon	4	4	31	6	22	1
Dompred-Domssea	44	33	8	5	1	5
Dompred-DPS	36	28	16	8	1	5
Dompro	46	35	12	6	0	0
Dopro	40	35	14	9	4	0
Globplot	48	34	5	3	1	4
Interproscan	51	38	6	4	1	0
Mateo	27	21	13	2	18	0
Ssep-domain	45	38	11	8	2	0
Robetta-Ginzu	36	33	13	9	9	0
Robetta-Rosettadom	36	34	16	12	6	0
CONSENSUS	42	37	14	11	2	0

2. Sensitivity and Specificity for single, two-domain and all targets

For each method, sensitivity (Sen) and specificity (Spec) have been calculated and plotted separately for single-domain targets, two-domain targets and finally for all targets as

Sen = TP / TP+FN

Spec = TP / TP+FP

where TP: Number of true positives; FN: Number of false negatives and FP: Number of false positives







3. Overlap Score (Single-Domain Targets)

Targets	Control1	Control2	Random	Adda	Armadillo	Biozon	Dompred-domssea	Dompred-dps	Dompro	Dopro	Globplot	Interproscan	Mateo	Ssep-domain	Robetta-ginzu	Robetta-rosettadom	Consensus
T0196	100.00	50.00	100.00	92.24	50.86	56.90	100.00	100.00	100.00	74.13	98.28	75.86	93.97	74.14	100.00	100.00	100.00
T0197	100.00	50.28	50.28	94.97	70.39	39.11	100.00	52.51	100.00	93.30	98.32	92.18	96.09	92.74	60.34	59.78	100.00
T0198	100.00	50.21	100.00	100.00	X	48.09	100.00	54.47	71.49	87.23	97.87	37.87	97.02	100.00	53.62	100.00	100.00
T0200	100.00	50.20	50.20	92.16	X	34.90	100.00	100.00	100.00	100.00	34.12	69.41	70.59	100.00	100.00	100.00	100.00
T0201	100.00	50.00	100.00	100.00	X	71.28	100.00	100.00	100.00	87.23	94.68	95.75	31.92	100.00	100.00	100.00	100.00
T0203	100.00	50.00	50.00	99.48	23.04	45.55	100.00	100.00	100.00	100.00	40.31	94.24	98.17	100.00	65.71	65.71	100.00
T0204	100.00	50.14	100.00	98.86	30.20	27.64	60.40	61.25	84.05	52.14	80.34	96.87	41.88	56.13	55.84	55.84	56.98
T0205	100.00	50.00	50.00	83.85	100.00	74.62	100.00	100.00	100.00	67.69	98.46	53.85	93.85	100.00	100.00	100.00	100.00
T0206	100.00	50.00	100.00	64.55	23.64	65.91	100.00	65.46	100.00	77.73	X	58.18	81.82	68.64	61.36	61.36	50.91
T0208	100.00	50.14	50.14	48.74	57.42	58.82	100.00	62.19	54.34	96.08	56.58	98.60	77.87	97.48	75.63	75.63	61.35
T0211	100.00	50.14	100.00	100.00	68.06	54.86	100.00	100.00	100.00	95.83	70.14	85.42	95.14	95.83	100.00	100.00	100.00
T0212	100.00	50.00	50.00	96.03	52.38	59.52	100.00	100.00	100.00	93.65	X	96.03	94.44	96.03	100.00	100.00	100.00
T0213	100.00	50.49	100.00	97.09	51.46	100.00	100.00	100.00	100.00	93.20	100.00	99.03	100.00	97.09	100.00	100.00	100.00
T0214	100.00	50.00	50.00	95.46	58.18	65.46	100.00	100.00	100.00	98.18	100.00	91.82	100.00	92.73	100.00	100.00	100.00
T0215	100.00	50.00	100.00	71.05	X	56.58	X	X	100.00	100.00	X	71.05	50.00	100.00	100.00	100.00	100.00
T0224	100.00	50.58	50.58	100.00	100.00	50.58	X	X	100.00	100.00	97.70	100.00	49.43	100.00	100.00	100.00	100.00
T0227	100.00	50.41	100.00	90.91	54.55	100.00	100.00	100.00	100.00	96.69	100.00	80.99	65.29	100.00	100.00	100.00	100.00
T0230	100.00	50.00	50.00	95.19	49.04	73.08	100.00	100.00	100.00	100.00	99.04	73.08	93.27	100.00	100.00	100.00	100.00
T0231	100.00	50.00	100.00	99.30	59.16	54.93	100.00	100.00	100.00	93.66	97.88	90.14	100.00	93.66	100.00	100.00	100.00
T0234	100.00	50.30	50.30	100.00	56.97	67.27	100.00	100.00	100.00	100.00	98.18	56.97	42.42	100.00	100.00	100.00	100.00
T0238	100.00	50.20	100.00	51.79	76.89	100.00	55.38	100.00	78.09	83.67	75.70	35.06	55.78	90.44	100.00	100.00	100.00
T0239	100.00	50.00	50.00	100.00	53.06	64.29	X	X	100.00	86.74	97.96	82.65	53.06	100.00	100.00	100.00	100.00
T0240	100.00	50.00	100.00	84.44	48.89	100.00	X	X	100.00	81.11	96.67	38.89	50.00	100.00	100.00	100.00	100.00
T0241	100.00	50.21	50.21	100.00	34.18	47.26	53.17	100.00	100.00	62.45	100.00	94.52	29.96	56.12	70.04	45.99	45.99
T0242	100.00	50.00	100.00	99.14	49.14	74.14	100.00	100.00	100.00	58.62	99.14	99.14	59.48	100.00	100.00	100.00	100.00
T0243	100.00	50.54	50.54	58.07	100.00	X	X	X	54.84	91.40	100.00	100.00	31.18	91.40	100.00	100.00	100.00
T0244	100.00	50.17	100.00	95.35	39.87	38.54	100.00	56.15	100.00	98.01	100.00	90.70	100.00	98.34	100.00	100.00	100.00
T0246	100.00	50.00	50.00	98.59	46.05	40.96	100.00	100.00	52.26	100.00	46.33	97.46	35.31	100.00	100.00	100.00	100.00
T0247	100.00	50.00	100.00	97.80	40.11	40.93	100.00	59.07	100.00	74.73	100.00	86.26	100.00	98.35	79.95	79.95	79.95
T0251	100.00	50.00	50.00	93.14	47.06	69.61	100.00	100.00	100.00	99.02	100.00	93.14	100.00	100.00	100.00	100.00	100.00
T0263	100.00	50.50	100.00	97.03	54.46	73.27	100.00	100.00	100.00	62.38	100.00	66.34	100.00	96.04	100.00	100.00	100.00
T0265	100.00	50.46	50.46	99.08	57.80	41.28	100.00	100.00	100.00	100.00	98.17	68.81	100.00	97.25	100.00	100.00	100.00
T0266	100.00	50.00	100.00	100.00	32.24	67.11	100.00	100.00	100.00	98.68	100.00	85.53	65.79	100.00	100.00	100.00	100.00
T0267	100.00	50.00	50.00	100.00	32.24	67.11	100.00	100.00	100.00	98.68	100.00	48.57	65.79	100.00	100.00	100.00	100.00
T0271	100.00	50.31	100.00	99.38	29.81	63.35	100.00	100.00	100.00	78.26	100.00	96.89	100.00	100.00	100.00	100.00	100.00
T0274	100.00	50.31	50.31	100.00	32.08	66.67	100.00	100.00	100.00	100.00	54.09	94.34	100.00	100.00	100.00	100.00	100.00
T0275	100.00	50.37	100.00	99.27	38.69	73.72	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00
T0276	100.00	50.00	50.00	94.02	48.91	42.39	100.00	100.00	100.00	78.26	44.02	89.13	26.09	100.00	100.00	100.00	100.00
T0277	100.00	50.42	100.00	91.60	48.74	53.78	100.00	100.00	100.00	98.32	100.00	97.48	45.38	100.00	100.00	100.00	100.00
T0281	100.00	50.00	50.00	85.71	100.00	58.57	100.00	100.00	100.00	100.00	X	78.57	100.00	65.71	100.00	100.00	100.00
T0282	100.00	50.00	100.00	97.59	X	63.86	100.00	71.39	100.00	99.10	92.77	86.47	87.95	95.48	100.00	100.00	100.00
Average	100.00	50.16	75.68	91.66	47.19	59.53	84.61	80.06	95.00	88.96	79.68	81.64	76.15	93.99	93.23	93.76	95.30

*X: No prediction

4. Plot of overlap score vs the percentage of correctly predicted single-domain targets

5. Overlap Score (Two-Domain Targets)

Targets	Control1	Control2	Random	Adda	Armadillo	Biozon	Dompred-domssea	Dompred-dps	Dompro	Dopro	Globplot	Interproscan	Mateo	Ssep-domain	Robetta-ginzu	Robetta-rosettadom	Consensus
T0199	74.56	75.15	74.56	74.56	X	98.82	91.42	92.01	74.56	69.53	74.56	85.50	70.41	88.17	92.01	63.61	89.94
T0202	61.85	87.95	87.95	61.85	X	61.04	61.85	61.85	61.85	61.85.62	61.04	56.63	54.62	61.85	43.37	67.07	61.85
T0209	50.63	99.58	50.63	87.87	60.25	75.73	50.63	87.87	85.77	79.50	49.79	43.52	67.78	88.70	89.12	50.63	89.12
T0216	51.49	98.39	98.39	51.49	66.21	54.02	51.49	79.77	75.63	97.47	72.18	44.37	55.63	73.33	63.91	86.44	99.08
T0222	84.72	65.42	84.72	84.72	59.25	34.32	98.39	87.94	84.72	84.72	84.72	80.97	84.72	96.78	93.30	93.30	93.30
T0223	58.25	91.75	91.26	58.25	84.47	89.81	58.25	58.25	58.25	58.25	57.77	58.25	58.25	58.25	58.25	58.25	58.25
T0228	65.04	84.85	65.04	64.80	50.58	54.55	95.80	46.85	55.94	82.75	64.57	62.01	63.40	61.77	85.32	85.32	77.62
T0229	68.12	81.88	81.88	68.12	92.03	68.12	68.12	68.12	68.12	68.12	66.67	65.94	84.06	68.12	94.93	94.93	68.12
T0232	63.98	86.02	63.98	68.22	85.17	65.25	97.46	63.98	63.98	77.97	63.14	49.58	63.98	84.32	99.58	99.58	95.76
T0233	83.43	66.58	66.58	82.87	20.99	59.67	89.78	96.69	97.51	87.02	82.87	83.15	74.86	90.06	95.30	95.30	94.48
T0235	75.95	73.95	75.95	64.13	59.92	65.33	75.95	75.75	53.51	91.18	75.95	87.98	48.70	96.59	47.90	47.90	47.90
T0249	61.72	88.04	88.04	61.72	63.64	68.42	93.30	61.72	61.72	73.68	61.72	43.54	75.60	91.39	97.61	96.65	99.52
T0262	67.97	82.03	67.97	67.97	67.58	68.36	67.97	67.97	89.45	92.58	56.64	63.28	67.97	60.16	68.36	70.31	83.98
T0264	60.54	89.46	89.46	60.54	55.10	67.69	60.54	70.75	60.54	47.28	60.54	40.82	54.42	60.54	98.30	98.30	79.93
T0269	58.80	91.20	58.80	78.80	44.00	72.40	58.80	96.80	58.80	70.00	57.60	56.00	80.00	82.00	92.00	92.00	91.60
T0272	59.24	90.52	90.52	59.24	82.46	98.58	59.24	59.24	59.24	59.24	58.29	59.24	41.23	59.24	59.24	93.37	59.24
T0273	79.14	70.59	79.14	79.14	56.15	62.57	79.14	79.14	79.14	79.14	55.62	79.14	79.14	79.14	79.14	75.94	79.14
Average	66.20	83.73	77.35	69.08	55.75	68.51	74.01	73.81	69.93	75.31	64.92	62.35	66.16	76.49	79.86	80.52	80.52

*X: No prediction

6. Plot of overlap score vs the percentage of correctly predicted two-domain targets

7. Plot of average overlap score vs the percentage of correctly predicted total targets





8. Prediction Performance Separately on HM and FR targets

Number of HM targets: 27
Number of HM targets which are single-domain: 20
Number of HM targets which are two-domain: 7

Number of FR targets: 31
Number of FR targets which are single-domain: 21
Number of FR targets which are two-domain: 10