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Childhood ‘Omics’ and Mycobacterium tuberculosis-derived BiOsignatures (COMBO) for TB diagnosis
The overall objective of the project is to identify Mtb- and/or host-derived biosignatures in children that can achieve World Health Organization (WHO) target product profile (TPP) accuracy thresholds for a non-sputum biomarker-based triage or diagnostic test for childhood TB. We hypothesize that biosignatures that combine Mtb proteins and host biomarkers will have the best diagnostic performance. To assess this hypothesis, we will conduct biomarker discovery using banked pediatric plasma and urine specimens from a diverse cohort from India, Uganda, South Africa, the Gambia and Peru. If successful, the results will be the first step needed to make progress toward addressing the critical unmet need for non-sputum biomarker-based tests for childhood TB.
Our overall objective is to identify biomarker signatures that meet recommended accuracy thresholds for a non-sputum, biomarker-based TB triage and/or diagnostic test.
- Quantify levels of known Mtb proteins using an ultra-sensitive Electrochemiluminescence (ECL)-based assay
- Perform an untargeted, shotgun proteomic and metabolomic approach to identify host proteins and metabolites that can serve as biomarkers for detection of childhood TB
- Derive and validate the diagnostic accuracy of Mtb and/or host biosignatures for childhood TB.