# A method for the culture-free discovery and host affiliation of novel viruses from metagenomic samples

> **NIH NIH R44** · PHASE GENOMICS, INC. · 2021 · $820,379

## Abstract

ABSTRACT
In this application, we propose to develop a novel reagent kit and accompanying analytic software platform that
employs Hi-C technology for a user-friendly method to assemble viral genomes from metagenomic samples and
associate these viruses with their microbial hosts. This product enables culture-free discovery of phages and
quantitative measurement of their host range directly in mixed microbial communities.
Bacteriophages are viruses that infect bacteria; they shape microbial ecosystems through predation on hosts
and through horizontal gene transfer. They are also an important vector in the transmission of anti-microbial
resistance. Despite their potent impact on microbial biology, only a tiny proportion of phage genomes are
represented in public databases in part because of the difficulty of isolating phage whose hosts are not culturable
laboratory settings. This limitation in our ability to understand viral biology has important impacts on emerging
biotechnology applications including fecal microbiota transplantation and phage therapy as well as wide-ranging
effects on microbiological research.
We propose to develop a novel computational approach combined with improved experimental methods to
deconvolute viral genomes and perform host attribution from whole microbiome samples without culturing. At
the core of this approach is utilization of proximity ligation methods (Hi-C) which physically associates DNA
sequences present within intact microbes. This provides direct physical evidence of the contiguity of viral
genome sequences and host affiliation information that is not achievable by any other method.
The outcome of this direct-to-Phase II proposal would be a combination of kit and user-facing computational
platform that would empower both the sophisticated next-generation-sequencing biologist and the sequencing
novice to ask important questions about viruses in their microbial community of interest. Aim 1 focuses on
computational methods improve the recovery of viral genomes from metagenomic data. Aim 2 develops
methodologies to enhance viral Hi-C chemistry. These two aims work together synergistically enhance data
quality. Finally, Aim 3 develops a computational platform for data analysis through a web portal where results
could be visualized directly via web browser or raw data downloaded for further exploration. Upon completion
we will have developed a first-in-class commercial platform to discover viral genomes and identify their hosts
from complex microbial communities.

## Key facts

- **NIH application ID:** 10259447
- **Project number:** 1R44AI162570-01
- **Recipient organization:** PHASE GENOMICS, INC.
- **Principal Investigator:** Ivan Liachko
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $820,379
- **Award type:** 1
- **Project period:** 2021-02-08 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259447

## Citation

> US National Institutes of Health, RePORTER application 10259447, A method for the culture-free discovery and host affiliation of novel viruses from metagenomic samples (1R44AI162570-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10259447. Licensed CC0.

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