# Leveraging within-host M. tuberculosis diversity data to enhance transmission inference

> **NIH NIH K01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $132,057

## Abstract

Project Summary
This application to the K01 Career Development Award is to support Dr. Katharine Walter in her training and
research into new methods for tuberculosis genomic epidemiology. Dr. Walter’s research focuses on
developing and applying tools to harness pathogen variation to characterize infectious disease transmission
and evolution in order to interrupt transmission in high-incidence, resource-poor settings. Dr. Walter’s research
proposal leverages within-host Mycobacterium tuberculosis genomic variation to reconstruct tuberculosis
transmission chains. Genomic epidemiology studies are increasingly used to characterize tuberculosis
transmission. However, current approaches have limited resolution because they sequence a single M.
tuberculosis genome from each infected individual. Despite the epidemiological and clinical significance of
within-host M. tuberculosis diversity, tools to consistently and accurately recover such diversity and to
incorporate this information into transmission inferences are lacking. This research proposal aims to (1)
systematically assess methods for recovering within-host diversity from sputum samples collected during
active screening in a high-incidence setting, (2) measure the M. tuberculosis diversity that is transmitted and
persists in a secondary infection, and (3) develop a model to infer transmission linkages using within-host M.
tuberculosis diversity data. The proposed project will leverage and expand upon the primary mentor’s NIH-
funded R01 studies (AI130058, AI149620; PI: Andrews). In a five-year training plan, Dr. Walter will acquire
skills in (1) statistical analysis and visualization of genomic data, (2) mathematical modeling of evolution and
transmission, and (3) writing open and reproducible bioinformatic workflows for genomic data. Dr. Walter will
be mentored by Dr. Jason Andrews, Associate Professor of Medicine at Stanford School of Medicine, a global
expert in the diagnosis, treatment and control of tuberculosis in resource-limited settings. She will be co-
mentored by Dr. Theodore Cohen, Associate Professor of Epidemiology of Microbial Diseases at the Yale
School of Public Health, whose research pioneered the study of mixed strain infections in M. tuberculosis. In
addition, Dr. Walter will collaborate closely with Dr. Julio Croda, an infectious disease physician-scientist and
Professor at Federal University of Mato Grosso do Sul, Brazil, who has extensive experiencing leading
prospective cohorts, genomic epidemiology studies, and clinical trials on tuberculosis and tropical diseases in
Brazil. She will also collaborate with Dr. Caroline Colijn, Professor of Mathematics at Simon Fraser University,
who has developed several statistical approaches for transmission inference. The results of this research and
training proposal will provide the foundation for a future R01 application, which will develop an automated
pipeline for real-time transmission inference and TB incidence estimation harnes...

## Key facts

- **NIH application ID:** 10751054
- **Project number:** 5K01AI173385-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Katharine Sassandra Walter
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,057
- **Award type:** 5
- **Project period:** 2022-12-08 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751054

## Citation

> US National Institutes of Health, RePORTER application 10751054, Leveraging within-host M. tuberculosis diversity data to enhance transmission inference (5K01AI173385-02). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/10751054. Licensed CC0.

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