# Quantitative Metagenomics and the Vaginal Microbiome of Preterm Birth

> **NIH NIH R35** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2021 · $285,178

## Abstract

Project Summary/Abstract
The Callahan laboratory develops quantitative and computational methods that improve the precision,
accuracy and reproducibility of marker-gene and metagenomics sequencing methods, and implements those
methods in open-source and actively supported software. The Callahan laboratory collaborates with other
research groups to investigate the role of host-associated microbial communities in various health problems,
with a particular focus on the role of the vaginal microbiome preterm birth.
Marker-gene and metagenomic sequencing methods have revolutionized the study of the human microbiome,
but the relative abundances of microbial taxa measured by these technologies are systematically distorted (or
“biased”) from the true relative abundances by experiment- and taxa-specific factors we do not understand.
Over the next five years we intend to solve the problem of bias in metagenomic sequencing via a multi-part
program that includes developing and validating an explanatory mechanistic model of bias in metagenomics
experiments, quantifying the sensitivity of downstream analysis methods to metagenomics bias and creating
new analysis methods unaffected by bias, and developing open-source software that allows researchers to
correct biased marker-gene and metagenomics measurements to their true values.
Recently, marker-gene and metagenomic sequencing methods have revealed that the vaginal microbiome of
pregnant women can predict risk of preterm birth. However, disagreements between studies on the specific
microbial signatures of preterm risk currently limit translation of these results. We intend to develop dense
longitudinal profiles with sub-species taxonomic resolution of the vaginal microbiota in hundreds of
pregnancies. We will define precise biomarkers of preterm risk as early in possible in pregnancy, and identify
candidate taxa that could be targeted as part of therapeutic interventions to reduce the rate of preterm birth.
We will synthesize the larger evidence base on this topic while controlling for the different metagenomics
biases in different studies in order to identify reproducible biomarkers of preterm birth risk. We will integrate the
longitudinal profiles of the vaginal microbiota with other omics measurements of host response to build
evidence for potential causative pathways between disturbances in the vaginal microbiota and preterm birth.
By developing computational and statistical methods that correct measurements of the microbiome to their true
values, the Callahan laboratory seeks to improve the precision and accuracy with which the wider research
community can characterize the human microbiome, thereby accelerating our understanding of microbiome-
related health conditions and the development of microbiome therapies that improve human health.

## Key facts

- **NIH application ID:** 10225413
- **Project number:** 5R35GM133745-03
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Benjamin John Callahan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $285,178
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225413

## Citation

> US National Institutes of Health, RePORTER application 10225413, Quantitative Metagenomics and the Vaginal Microbiome of Preterm Birth (5R35GM133745-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225413. Licensed CC0.

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