Phenotypic profiles	R	S	U	F	Total	R	S	U	F	Total	Prevalence of resistance among each of the listed drug profiles, %	Sensitivity, %	Specificity, %	PPV, %	NPV,%	Expected NPV at given prevalence of resistance based on simulations, % (95% CI)*	Calculated NPV at 20% prevalence of resistance, % (see table S3)	Calculated NPV at 40% prevalence of resistance, % (see table S3)
Isoniazid	-SSS	391	30	18	12	451	21	4,653	133	104	4,911	8.4	93	100	95	99.4	99.3-100	98.2	95.4
	-RSS	459	21	20	6	506	7	85	5	1	98	83.8	96	92	98	80.2	83.5-100	98.8	96.9
	-RRS	424	3	13	4	444	2	2	2	0	6	98.7	99	50	100	40.0	73.7-85.6	99.6	99.1
	-SRS	24	4	1	0	29	0	10	1	0	11	72.5	86	100	100	71.4	90.5-95.6	96.6	91.3
	-SSR	24	1	2	1	28	0	95	6	3	104	21.2	96	100	100	99.0	98.5-99.7	99	97.4
	-RRR	662	3	11	4	680	0	0	0	0	0	100.0	100	.	100	0.0	73.7-85.6	n/a	n/a
	-RSR	217	3	5	5	230	0	3	0	0	3	98.7	99	100	100	50.0	73.7-85.6	99.7	99.1
	-SRR	13	0	0	2	15	0	0	0	0	0	100.0	100	.	100	.	73.7-85.6	n/a	n/a
Rifampicin	S-SS	74	16	0	8	98	30	4,632	126	123	4,911	2.0	82	99	71	99.7	99.3-100	95.7	89.3
	S-RS	6	0	0	0	6	1	9	1	0	11	35.3	100	90	86	100.0	97.8-99.5	100	100
	S-SR	1	2	0	0	3	0	100	3	1	104	2.8	33	100	100	98.0	99.3-100	85.7	69.2
	S-RR	0	0	0	0	0	0	0	0	0	0	.	.	.	.	.	.	n/a	n/a
	R-SS	464	20	1	21	506	18	424	3	6	451	52.9	96	96	96	95.5	95.8-98.6	98.9	97.2
	R-RS	424	7	2	11	444	4	25	0	0	29	93.9	98	86	99	78.1	76.2-86.6	99.5	98.8
	R-SR	218	4	0	8	230	7	20	0	1	28	89.1	98	74	97	83.3	77.9-87.9	99.4	98.4
	R-RR	665	2	0	13	680	10	3	0	2	15	97.8	100	23	99	60.0	76.2-86.6	99.7	99.1
Ethambutol	SS-S	1	9	1	0	11	4	4,399	472	36	4,911	0.2	10	100	20	99.8	98.8-99.9	81.6	62.5
	RS-S	21	5	3	0	29	31	376	40	4	451	6.0	81	92	40	98.7	98.8-99.9	95.1	87.8
	SR-S	4	2	0	0	6	1	93	3	1	98	5.8	67	99	80	97.9	98.8-99.9	92.2	81.7
	RR-S	375	20	30	19	444	203	241	48	14	506	46.7	95	54	65	92.3	93.4-96.7	97.7	94.1
	SS-R	0	0	0	0	0	1	81	22	0	104	0.0	.	99	0	100.0	98.8-99.9	n/a	n/a
	RS-R	12	2	1	0	15	7	20	1	0	28	34.9	86	74	63	90.9	95.7-98.1	95.4	88.6
	SR-R	0	0	0	0	0	0	3	0	0	3	0.0	.	100	.	100.0	98.8-99.9	n/a	n/a
	RR-R	625	9	26	20	680	150	50	25	5	230	74.7	99	25	81	84.7	82.0-88.2	98.6	96.4
Pyrazinamide	SSS-	74	28	0	2	104	12	4,826	13	60	4,911	2.1	73	100	86	99.4	98.6-99.6	93.6	84.5
	RSS-	13	8	4	3	28	5	431	2	13	451	5.8	62	99	72	98.2	98.6-99.6	91.2	79.6
	RRS-	166	25	22	17	230	49	374	68	15	506	31.3	87	88	77	93.7	95.5-97.7	96.4	91
	SRS-	0	3	0	0	3	0	97	0	1	98	3.0	0	100	.	97.0	98.6-99.6	80	60
	RRR-	532	15	83	50	680	107	216	105	16	444	60.5	97	67	83	93.5	87.3-91.0	99	97.3
	SRR-	0	0	0	0	0	0	6	0	0	6	0.0	.	100	.	100.0	98.6-99.6	n/a	n/a
	RSR-	10	2	1	2	15	0	28	0	1	29	34.1	83	100	100	93.3	95.0-97.3	96	90
	SSR-	0	0	0	0	0	0	11	0	0	11	0.0	.	100	.	100.0	98.6-99.6	n/a	n/a

Phenotypic profiles are listed in the following order: Isoniazid, Rifampicin, Ethambutol, Pyrazinamide. '-' under 'Phenotypic profiles' marks the drug phenotype being assessed. PPV = Positive Predictive Value; NPV = Negative Predictive Value; R=resistant; S=susceptible; U=mutation of unknown association present; F=genotypic prediction failed due to missing data around a genomic resistance locus; All % results based on R/S genotypic predictions only, excluding U and F. Expected NPV was calculated as follows: specificity x (1-prevlence) / (specificity x (1-prevlence)+(1-sensitivity) x prevalence). * indicates that for prevalence <10% or >90%, simulated values are given for 10% and 90% respectively as simulations were not performed below or above these values.