. 2021 Mar;21(3):366–375. doi: 10.1016/S1473-3099(20)30928-2

Table 3.

Diagnostic performance of cohort-derived signatures and previously published signatures in patients with tuberculosis diagnosis

		Gene signature	Comparison groups	Previously reported performance of published signatures				All active tuberculosis vs other disease (n=628)			Culture-confirmed pulmonary tuberculosis vs other disease (n=224)			Highly-probable tuberculosis vs other disease (n=178))			Extrapulmonary tuberculosis vs other disease (n=328)
				Cohort site (size)^*^†	AUC-ROC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)	AUC-ROC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)	AUC-ROC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)	AUC-ROC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)	AUC-ROC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)
Signature 1		13 transcripts^‡^§	..	..	..	..	..	0·87 (0·81–0·92)	0·77 (0·66–0·87)	0·84 (0·74–0·91)	0·88 (0·77–0·96)	0·82 (0·65–0·95)	0·83 (0·68–0·96)	0·80 (0·66–0·93)	0·72 (0·47–0·92)	0·75 (0·52–0·93)	0·86 (0·78–0·94)	0·76 (0·61–0·91)	0·82 (0·68–0·94)
Signature 2		20 transcripts^‡^§	..	..	..	..	..	0·85 (0·78–0·90)	0·77 (0·65–0·87)	0·82 (0·72–0·90)	0·86 (0·74–0·95)	0·75 (0·63–0·90)	0·82 (0·63–0·96)	0·77 (0·63–0·89)	0·68 (0·44–0·88)	0·74 (0·53–0·93)	0·83 (0·73–0·91)	0·78 (0·61–0·92)	0·78 (0·62–0·93)
Signature 3		FCGR1C, GBP5, UB2L6	..	..	..	..	..	0·84 (0·78–0·91)	0·75 (0·64–0·85)	0·81 (0·72–0·90)	0·87 (0·76–0·95)	0·80 (0·62–0·95)	0·78 (0·62–0·95)	0·80 (0·66–0·92)	0·70 (0·47–0·89)	0·79 (0·56–0·94)	0·84 (0·74–0·92)	0·74 (0·58–0·88)	0·79 (0·66–0·93)
Kaforou et al⁷		Disease Risk Score 44 transcripts	Tuberculosis (culture-confirmed) vs other diseases	Malawi (n=471)	1 (1–1)	1 (1–1)	0·96 (0·93–1)	0·81 (0·78–0·85)	0·74 (0·69–0·79)^†	0·77 (0·72–0·81)	0·85 (0·80–0·90)	0·75 (0·66–0·83)^†	0·87 (0·79–0·92)	0·70 (0·63–0·78)	0·76 (0·66–0·85)^†	0·61 (0·50–0·71)	0·79 (0·74–0·84)	0·73 (0·66–0·80)^§	0·78 (0·71–0·84)
Anderson et al⁶		Disease Risk Score 51 transcripts	Tuberculosis (composite) vs other diseases (in children)	South Africa, Malawi, and Kenya (n=503)	0·89 (0·82–0·95)	0·83 (0·69–0·94)	0·83 (0·73–0·92)	0·68 (0·64–0·72)	0·75 (0·70–0·80)^¶	0·50 (0·46–0·58)	0·67 (0·60–0·74)	0·74 (0·65–0·82)^¶	0·51 (0·41–0·60)	0·63 (0·55–0·71)	0·60 (0·49–0·70)^¶	0·56 (0·45–0·67)	0·69 (0·63–0·75)	0·77 (0·70–0·83)^‖	0·52 (0·44–0·60)
Sweeney et al⁸		TB risk score DUSP3, GBP5, KLF2^**	Tuberculosis (culture-positive or smear-positive) vs other diseases^††	..	..	..	..	0·83 (0·80–0·86)	0·78 (0·73–0·83)^‡‡	0·76 (0·70–0·80)	0·86 (0·81–0·91)	0·75 (0·66–0·83)^‡‡	0·88 (0·81–0·94)	0·71 (0·64–0·79)	0·76 (0·66–0·85)^‡‡	0·62 (0·51–0·72)	0·83 (0·78–0·87)	0·85 (0·79–0·90)^§§	0·70 (0·63–0·77)
	German validation cohort	..	..	Germany (n=1067)	0·75 (0·65–0·86)	0·50	0·61	..	..	..	..	..	..	..	..	..	..	..	..
	Kenyan validation cohort	..	..	Kenya (n=1180)	0·91 (0·88–0·95)	0·77	0·86	..	..	..	..	..	..	..	..	..	..	..	..
	South African validation cohort	..	..	Malawi and South Africa (n=1357)	0·82 (0·79–0·84)	0·69	0·74	..	..	..	..	..	..	..	..	..	..	..	..

AUC-ROC=area under the receiver-operating characteristic curve.

Reported size of cohorts includes the derivation cohort (comprising a training set and test set) and the validation cohort.

^†

Youden Index cutoff was 110·21, 106·00, and 108·60.

^‡

See appendix (pp 4–5) for full transcript lists.

^§

Youden Index cutoff was 108·36.

^¶

Youden Index cutoff was 92·18, 92·38, and 91·44.

^‖

Youden Index cutoff was 91·44.

^**

The Sweeney et al⁸ signature was derived using the combination of three discovery cohorts comprising 1023 participants, then applied separately to three validation cohorts (each reported in table with size including the 1023 shared discovery cohorts).

^††

Other comparisons not reported in this table include active tuberculosis versus healthy controls and active tuberculosis versus latent tuberculosis infection.

^‡‡

Youden Index cutoff was −2·82, −3·48, and −3·23.

^§§

Youden Index cutoff was −3·48.