# Host Proteomic Biosignatures for a Urine-based Diagnosis of Pulmonary Tuberculosis in Children

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $209,400

## Abstract

PROJECT ABSTRACT
Tuberculosis (TB) is a leading cause of mortality in children worldwide. Difficulty in obtaining sputum and a low
sputum bacillary load are major barriers to diagnosis, and necessitate the development of a non-sputum,
biomarker-based assay for childhood intrathoracic TB disease. Host biomarker discovery for childhood TB
requires a greater focus on downstream proteins and their post-translational modifications (PTMs) that are more
likely to be specific to a disease phenotype and can be more easily translated into a point-of-care test. With the
support of this K23 award, Dr. Devan Jaganath will identify a host proteomic biosignature in urine that can
achieve the goal accuracy for a triage and/or diagnostic test for pulmonary TB in children. To complete this
objective, he will leverage an ongoing prospective cohort of symptomatic children being evaluated for
intrathoracic TB in Kampala, Uganda, with the extensive proteomic facilities available at the University of
California, San Francisco (UCSF). In Aim 1, he will perform targeted mass spectrometry on urine samples from
children with confirmed vs. unlikely TB, and examine the abundance and ubiquitylation of 10 host proteins that
have prior evidence of specific interactions with M. tuberculosis (Mtb) proteins as candidate biomarkers. In Aim
2, he will use shotgun mass spectrometry on the urine samples to identify all host proteins and their PTMs that
can differentiate TB status as novel biomarkers, and perform pathway analysis to determine the subset with
functional relevance to Mtb pathogenesis. In Aim 3, he will apply machine learning analyses to identify the
smallest combination of biomarkers that can achieve the target accuracy thresholds for a triage and/or diagnostic
test for intrathoracic TB disease. He will then evaluate the performance of promising biosignatures in an
independent, prospectively enrolled test set. Through this approach, Dr. Jaganath seeks to optimize biomarker
discovery for childhood TB diagnosis by coupling prospective clinical cohorts with a targeted and untargeted
high-throughput approach to comprehensively examine non-sputum samples for host biomarkers for children.
Dr. Jaganath's career goal is to be a physician scientist who translates non-sputum biomarkers into clinical tools
that can improve the care of children with TB. To support his path to independence, the proposed work will be
paired with a dedicated, multidisciplinary mentorship team and training in international pediatric TB biomarker
studies, bioinformatics for proteomic analysis, and machine learning. UCSF is an outstanding environment that
is committed to junior investigators with extensive resources for research and career development, and Mulago
National Referral Hospital in Uganda is a leader in pediatric TB research, and has the established infrastructure
for ongoing enrollment and sample collection. The findings will support an NIH R01 application to validate the
biomarkers and biosig...

## Key facts

- **NIH application ID:** 10038668
- **Project number:** 1K23HL153581-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Devan Jaganath
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,400
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038668

## Citation

> US National Institutes of Health, RePORTER application 10038668, Host Proteomic Biosignatures for a Urine-based Diagnosis of Pulmonary Tuberculosis in Children (1K23HL153581-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038668. Licensed CC0.

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