Next-gen sequencing company Longas publicly launches

Longas Technologies, a developer of next-generation sequencing (NGS) technologies, last month emerged from stealth mode, unveiling its Morphoseq technology and announcing the appointment of Nick McCooke as its CEO.

Longas is a spinout from the ithree institute at the University of Technology Sydney (UTS), funded by the Medical Research Commercialisation Fund (MRCF) and investment from the company’s founders and directors. Co-founders include computational biologist Professor Aaron Darling — now CSO at the company — Dr Catherine Burke and Professor Ian Charles, previously director of the ithree institute.

Morphoseq, meanwhile, is a disruptive technology designed to improve the performance of industry-standard NGS platforms by increasing effective read lengths, with benefits in accuracy and cost efficiency. Originally driven by a need for better 16S rDNA sequence-based resolution for microbial community profiling, the technology was soon found to be able to increase the effective read length from established NGS platforms.

“The rise of high-throughput, low-cost DNA sequencing has made genome sequencing routine and affordable, but has come at the cost of read length,” said Prof Darling. “It is very difficult for assembly methods to resolve genomic repeats that are longer than the read length. But long repeats are present at many of the most clinically informative parts of genomes, such as drug resistance genes in bacteria and the MHC locus in humans. The ability to accurately assemble and phase these into individual chromosomes for humans and microorganisms has important clinical and epidemiological applications.”

Developed by a team led by Prof Darling, Morphoseq chemistry works by creating unique identifiers for every long DNA template molecule in a sample via highly uniform random mutagenesis. Short read sequences can then be assigned to long templates, with the sophisticated data processing algorithms reconstructing the original unmutated long template molecules.

Morphoseq thus transforms short read sequencers into ‘virtual long read’ sequencers, enabling finished-quality genome assemblies with high accuracy — including resolution of difficult-to-assemble genomic regions. It works with as little as 10 ng of DNA and has the flexibility to scale to large genomes and large sample batches.

“Morphoseq makes high-quality long read DNA sequencing accessible and cost-effective,” said Prof Darling. “It delivers highly accurate long DNA sequences at a fraction of the cost of existing long read platforms. With modest DNA input requirements and a standard short read DNA sequencer, Morphoseq can produce finished de novo genome assemblies, including through repetitive regions in genomes such as tandem repeats and transposable elements. Sample preparation can be carried out with standard molecular biology consumables and equipment, and our cloud-based end-to-end analysis pipeline returns best-in-class long reads at the push of a button.”

The company has demonstrated long reads up to 15 Kbps with modal accuracy 100% and 92% of reads >Q40 when measured against independent reference genomes. These results, on a set of 60 multiplexed bacterial isolates, show that genomic coverage is highly uniform with the data yielding finished-quality closed circle assemblies for bacterial genomes across the entire GC content range. Further studies have demonstrated the ability to accurately assemble and phase these DNA reads into individual chromosomes for humans as well as microorganisms, with important scientific, clinical and public health applications.

Having now finally emerged from stealth mode, Longas is seeking partners and collaborators to support commercialisation, with McCooke (a non-executive director of the company since 2015) taking on the role of CEO to lead commercialisation and industry partnering. As founding CEO of Solexa, he led the development of the world’s leading NGS technology prior to the company being acquired by Illumina. Currently pursuing a portfolio career, with a focus on disruptive genomics technologies, he is also a non-executive director of Evonetix and Bioventix.

“As its speed and accuracy increases, and cost reduces, DNA sequencing is having a massive impact in a wide number of fields,” McCooke said. “There is an expanding opportunity for technologies that work in tandem with the main sequencing platforms, improving key aspects of their performance.”

Longas Chairman Dr Stephen Thompson, Managing Director at MRCF manager Brandon Capital, added, “Longas is an exciting opportunity that could help transform the research, epidemiology and clinical genomics fields. Its technology solves a key problem in NGS and promises to have an important impact within the NGS market — a market that is expected to grow from US$5.7 billion last year to US$20 billion by 2025.”

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