# Accessible high-throughput single-cell genome sequencing

> **NIH NIH R33** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $361,588

## Abstract

PROJECT SUMMARY
Initiation and evolution of most solid tumors involve complex genomic rearrangements in addition to point
mutations – all of which can contribute to cancer progression and to the evolution of resistance to therapeutics.
Single-cell whole genome sequencing (scWGS) has proven invaluable for the identification of tumor
subpopulations and in advancing our understanding of clonal dynamics and tumor evolution. Despite the value
of scWGS, there is a dearth of commercially-available options that provide enough cell throughput (i.e. power)
and/or genomic coverage to fully catalogue and characterize clonal populations within a tumor sample. This
can be particularly problematic when rare, possible therapy-resistant, subpopulations are present within a
tumor that may elude detection using existing methodologies.
Here we will solve the accessibility problem by developing technologies that leverage widely-available
instrumentation and off-the-shelf reagents. We previously described proof-of-principle technologies to construct
scWGS libraries contained within the nucleus (in situ) of each cell that are then carried through cell barcoding
using our custom workflow. We will extend, develop, and adapt these technologies to provide three workflows
that will meet the needs of the cancer research community by providing readily-accessible order-of-magnitude
improvements to cell throughput, cell coverage and cost savings for scWGS analysis over current options. The
first is focused on high cell throughput using widely available instrumentation; the second leverages our high-
content chemistry to produce high-coverage single cell genomic profiles with reduced reagents and improved
throughput; and finally, the third approach implements target capture to target exonic sequence or other
regions of interest to reduce sequencing costs. Each of these is targeted to meet the needs of specific areas of
cancer research, from basic science to clinical, and share the theme of accessibility.

## Key facts

- **NIH application ID:** 10819200
- **Project number:** 5R33CA269015-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrew Adey
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $361,588
- **Award type:** 5
- **Project period:** 2022-04-21 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819200

## Citation

> US National Institutes of Health, RePORTER application 10819200, Accessible high-throughput single-cell genome sequencing (5R33CA269015-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10819200. Licensed CC0.

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