Although study site-specific biosignatures had high accuracy for TB, a site-independent 5-marker biosignature (G-CSF, C3b/iC3b, procalcitonin, IP-10, PDGF-BB) was identified diagnosing TB with a sensitivity of 72.7% (95% CI, 49.8–82.3) and specificity of 90.5% (95% CI, 69.6–98.8) irrespective of geographical site. The gene discussed is C3; the disease is tuberculosis.