# A next-generation method for cytogenomics using Hi-C proximity ligation sequencing

> **NIH NIH R44** · PHASE GENOMICS, INC. · 2022 · $837,867

## Abstract

ABSTRACT
Reproductive genetic tests are a disparate collection of methodologies with identify specific classes of mutations
known to interfere with gametogenesis, conception and fetal viability. The number and variety of tests addressing
this clinical need reflect the scale of genetic lesions that are relevant to reproductive medicine, ranging from
whole chromosome aneuploidy to single nucleotide variants. In this proposal, we describe a highly scalable
reproductive genetic test that can deliver results that span this scale at high resolution, lower cost, and faster
turnaround time than current tests.
Our approach uses a proximity ligation DNA sequencing method called Hi-C, which captures ultra-long-range
genomic contiguity information using ubiquitious short-read sequencing and benchtop molecular biology. We
have demonstrated extensively that Hi-C data can be used to order and orient genome assemblies,
reconstructing end-to-end chromosome sequences. This method also identifies structural genomic
rearrangements including balanced translocations, inversions, and other aberrations not detectable by typical
sequencing approaches.
We propose to apply high-throughput proximity ligation as a cytogenomic method to detect the breadth of
chromosomal aberrations at high resolution and low cost. This proposal outlines a path to a commercially
available product and service, which will establish a highly validated method for use in research and eventually
in a diagnostic setting. This will be accomplished by 1) designing an easy to use Hi-C protocol amenable to
multiwell plate handling, 2) building a robust computational platform to reproducibly call chromosome aberrations
from Hi-C data, and 3) proving the validity and reproducibility of these methods on real world samples. The
resulting kit and software product will be a new cytogenomic method called Karyotyping by SequencingTM (KBS)
that we will deploy as a Precision Medicine test for the reproductive testing market.

## Key facts

- **NIH application ID:** 10397703
- **Project number:** 5R44HD104323-03
- **Recipient organization:** PHASE GENOMICS, INC.
- **Principal Investigator:** Stephen Matthew Eacker
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $837,867
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397703

## Citation

> US National Institutes of Health, RePORTER application 10397703, A next-generation method for cytogenomics using Hi-C proximity ligation sequencing (5R44HD104323-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10397703. Licensed CC0.

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