Commercialization of a low-cost user-friendly DNA preparation kit that produces chromosome-span
contiguity from conventional short-read sequencing for a wide range of applications
Arima Genomics
7. Project Summary/Abstract
Over 90% of Next-Generation Sequencing (NGS) is sequenced via Illumina short-read sequencers. This is
because of its cost-effectiveness and faster turn-around times. However, short-read sequencing technologies
lose critical contiguity information and are limited in assembling genomes de novo and reconstructing maternal
and paternal haplotypes of diploid genomes. Contiguity information is valuable for understanding the genetics
of human health and disease, and therefore critical for advancing precision and personalized medicine. Long-
read technologies (e.g. Pacific Biosciences) only reach megabase-scale chromosomal contiguity, but are 5-7X
more expensive than Illumina short-read, limiting its use. Recent advances in DNA preparation can preserve
long-range information that is compatible with Illumina short-read sequencing. These “synthetic” long-reads (or
SLR) methods can improve short-read technologies with, long-range contiguity and short-read economy.
However, the maximal SLR contiguity is only 1-5% the contiguity a 100Mb average human chromosome. To
construct multi-megabase contiguity, SLR methods require genomic DNA (gDNA) fragments >100-150Kb, but
obtaining long gDNA fragments is challenging and this limits current SLR methods. Arima Genomics has
repurposed HiC technology as an SLR-based DNA preparation kit that preserves chromosome-span contiguity
and haplotype phasing that is short-read compatible. Arima key technical innovation is, rather than using
purified gDNA, our method leverages the long-contiguity information preserved naturally in the 3-dimensional
(3D) organization of genomes in cells, as 3D information is long-range information. By capturing 3D genome
information, Arima's Contigo kit reconstructs chromosome-span information. The Contigo kit from Arima
therefore has complete contiguity with short-read economy. The Contigo kit is affordable, does not require
esoteric reagents, additional skills or equipment, and is compatible with exiting short-read workflows, to offer
easy user adoption. In addition, Contigo is the only kit to preserve 3D genomic information essential to
interpreting non-coding functional genomics. The Contigo kit has the potential to serve as a new standard in
next-generation sequencing with broad applications in genotyping, phasing, allele-specific gene expression
and epigenetics on phased genomes, structural variation analyses, metagenomics and 3D genomics. In this
proposal we will commercialize the Contigo technology by improving sensitivity to wide range of cell-inputs and
uniformity in genome coverage, and enabling 96-well compatibility. In addition, we will design for manufacture,
reduce cost and improve sourcing, assure robust performance in real-world shipping and storage conditions,
improve user-experience, and finally, benchmark performance of the Contigo kit with domain experts, key
opinion leaders, and power users to demonstrate commercial viability.
