# Chromosomal aberration detection in FFPE tissue using proximity ligation sequencing

> **NIH NIH R44** · PHASE GENOMICS, INC. · 2024 · $1,141,676

## Abstract

ABSTRACT
The detection of chromosomal aberrations is a frontline diagnostic for the spectrum of blood neoplasms.
Chromosomal aberrations, such as translocations, inversions, deletions and insertions, have been historically
identified using cytogenetic methods or more recently through application of long read sequencing or optical
mapping technologies. These methods have been less applicable in solid tumor research and diagnostics
because they require either viable cells or high-molecular weight DNA. The vast majority of solid tumor
biopsies are stored in formalin-fixed paraffin-embedded (FFPE) blocks, a process that highly fragments
genomic DNA. In this proposal we describe a low-cost and scalable method compatible with FFPE tissue that
enables the detection of chromosomal aberration using proximity ligation sequencing.
Proximity ligation methods such as chromosome conformation capture (3C) and Hi-C can be used to order and
orient segments of genomes, reconstructing end-to-end chromosome sequences. When a sequence deviates
from the expected order or orientation, such as is in the case of chromosomal aberrations, the sequence
appears as an obvious off-diagonal signal on a Hi-C heatmap, making identification of chromosomal
abnormalities an automatable process.
We propose to apply 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 FFPE Hi-C protocol amenable to multiwell
plate handling, 2) building a robust automated platform to reproducibly call chromosome aberrations from Hi-C
data, and 3) proving the validity and reproducibility of these methods on real world sample. The result of these
efforts will be a new cancer cytogenetics methodology called Karyotyping by SequencingTM (KBS).

## Key facts

- **NIH application ID:** 10934589
- **Project number:** 5R44CA281528-02
- **Recipient organization:** PHASE GENOMICS, INC.
- **Principal Investigator:** Stephen Matthew Eacker
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,141,676
- **Award type:** 5
- **Project period:** 2023-09-25 → 2025-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934589

## Citation

> US National Institutes of Health, RePORTER application 10934589, Chromosomal aberration detection in FFPE tissue using proximity ligation sequencing (5R44CA281528-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10934589. Licensed CC0.

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