A Nine-gene Blood-based Signature Meets the World Health Organization (WHO) Target Product Profiles for Diagnosis of Active Tuberculosis and Predicting Progression from Latent to Active Disease

Thursday, June 23, 2022

1:50 PM – 2:05 PM PT

Location: Salons 3/4

Authors: Sanjana Gupta, PhD (Presenting Author) - Stanford University; Aditya Rao, PhD (Co-Author) - Stanford University; Madeleine Scott, PhD (Co-Author) - Stanford University; Valeriu Crudu, MD, PhD (Co-Author) - Nicolae Testemitanu State University of Medicine and Pharmacy; Timothy Rodwell, MD, PhD, MPH (Co-Author) - University of California San Diego; Donald Catanzaro, PhD (Co-Author) - University of Arkansas; Antonino Catanzaro, MD (Co-Author) - University of California, San Diego; Purvesh Khatri, PhD (Co-Author) - Stanford University

Presenting Author(s)

SG

Sanjana Gupta, PhD

Postdoctoral Researcher
Stanford University
Sunnyvale, California, United States

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Chair(s)

YV

Yanet Valdez Tejeira, PhD

As part of its End TB strategy, the WHO has identified the need for non-sputum-based diagnostics that meet target product profiles (TPP) of 90% sensitivity and 70% specificity for diagnosis of ATB and 75% sensitivity and specificity for predicting progression from LTB to ATB. The successful translation of a 3-gene blood-based signature, identified using diverse datasets, into a prototype point-of-care diagnostic that meets the WHO TPPs, has demonstrated the power of integrating large amounts of heterogeneous data to identify generalizable disease signatures. We hypothesized that integration of more diverse datasets, comprising patients with ATB or other inflammatory lung diseases (e.g., COPD, viral infections, sarcoidosis, lung cancer, etc.), would identify novel robust signatures, for diagnosing ATB and predicting progression from LTB to ATB, that meet the WHO TPPs.

By integrating data from 3615 peripheral blood samples across 49 publicly available transcriptomic datasets, we identified a 9-gene signature for diagnosing ATB patients from healthy controls, or individuals with LTB or other diseases. The signature achieved 90.1% sensitivity and 81.7% specificity in retrospective validation cohorts (3836 blood samples, 28 datasets) and 90.2% sensitivity and 68.9% specificity in a prospective cohort from Moldova (360 blood samples). In a longitudinal cohort of adolescents, the 9-gene signature predicted progression from LTB to ATB up to 1 year prior to sputum conversion with 76% sensitivity and 83.3% specificity. Finally, the signature predicted prolonged lung inflammation in the Catalysis Treatment Response Cohort. Overall, the 9-gene signature meets the WHO TPPs required for the End TB strategy.