HeptaTB Dx: a diagnostic model leveraging cuproptosis-ferroptosis crosstalk for distinguishing latent from active tuberculosis

The differentiation between latent tuberculosis infection (LTBI) and active tuberculosis (TB) is a persistent challenge in global TB control, with current diagnostics failing to reliably distinguish these states or predict progression. This study introduces the HeptaTB Dx Model, the first diagnostic signature derived from the crosstalk between cuproptosis and ferroptosis-two metal-dependent regulated cell death pathways with emerging roles in <i>Mycobacterium tuberculosis</i> pathogenesis. By integrating seven key genes (MT1G, SCO2, CREB5, MGST1, PARP9, ATF3, and MUC1), the model achieves high diagnostic accuracy (area under the curve up to 0.963) and provides mechanistic insights into immune-metabolic dysregulation during TB infection. Validated in both public datasets and prospective clinical cohorts, HeptaTB Dx offers a scalable, transcriptome-based tool that outperforms existing single-pathway models and protein-based assays. This work not only advances TB diagnostics but also illuminates novel pathogenic mechanisms involving copper-iron interplay, with potential implications for therapeutic targeting.