# Rapid Method to Enhance and Shape Long-Read Sequencing Read Length Distributions

> **NIH NIH R44** · CIRCULOMICS, INC. · 2020 · $859,318

## Abstract

Project Summary
By offering the ability to analyze long stretches of DNA spanning hundreds of kb to Mb in length, 3rd generation
and linked-read sequencing technologies from PacBio, Oxford Nanopore, and 10X Genomics have begun to
revolutionize an increasing number of genomics applications including de novo assembly, phasing/scaffolding,
and structural variant analysis. These capabilities are predicated on the ability to efficiently manipulate high
molecular weight (HMW) DNA. Not only must HMW DNA be extracted, but it is equally important that it is not
damaged or lost during subsequent library preparation. For optimal sequencing read length, throughput, and
quality, precise control of insert lengths is crucial. In Oxford Nanopore sequencing, elimination of short DNA can
be used to increase mean read lengths and enhance the fraction of ultra-long reads (>100 kb). In PacBio HiFi
sequencing, tight control of insert size allows the generation of high consensus accuracy (>QV20) single
molecule reads. Previously, the only method to perform such size selection of DNA in the 10-100 kb range was
through manual or, more commonly, automated gel purification. Gel purification instruments have high cutoffs
but are slow, expensive, and have low recovery of long DNA. During the course of developing our Nanobind
DNA extraction technology, we invented Short Read Eliminator (SRE) size selection technology and
quickly brought it to market. In only 9 months of commercial sales, it has become a leading method of size
selection for nanopore sequencing due to its high performance, low cost, and ease of use. To achieve this,
Circulomics developed proprietary polymer chemistries that enable high cutoffs, high recovery of HMW DNA,
and rapid processing. In this Direct to Phase II proposal, we will expand the Short Read Eliminator product
portfolio to enable users to further shape read length distributions and address a wider range of
sequencing workflows. We will develop new versions of Short Read Eliminator: 1) with higher and sharper
cutoffs, 2) for band-pass size selection, 3) for low input samples, and 4) to partition DNA and RNA from the same
biological sample. These new versions of the Short Read Eliminator will be validated on both PacBio and Oxford
Nanopore using a variety of sample types and applications.

## Key facts

- **NIH application ID:** 10080760
- **Project number:** 1R44HG011445-01
- **Recipient organization:** CIRCULOMICS, INC.
- **Principal Investigator:** Kelvin Liu
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $859,318
- **Award type:** 1
- **Project period:** 2020-08-04 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080760

## Citation

> US National Institutes of Health, RePORTER application 10080760, Rapid Method to Enhance and Shape Long-Read Sequencing Read Length Distributions (1R44HG011445-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10080760. Licensed CC0.

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