17 November 2021
George Coe By George Coe

The NGS Landscape: The Long and Short of It.

Next-generation sequencing (NGS) is a technology used to determine the order of nucleotides in entire genomes or targeted regions of DNA or RNA. This parallel sequencing technology offers ultra-high throughput, scalability, and speed. It has revolutionised biological sciences by allowing labs to study biological systems at a level that was never previously possible.

When applied to the novel coronavirus, new strains can be detected using NGS without prior organism knowledge. As a result, it has been a busy couple of years in the NGS space, with the market seeing continued growth due to constant ‘COVID variant surveillance’.

The next decade is shaping up to bring about huge changes in the industry, and Illumina remain dominant company leading innovation in the market. Providing developers and researchers with evidence which allows tracking of a wide variety of transmission routes and mutations, NGS has been a crucial factor in ensuring effective vaccination development for COVID.

What is sequencing read length?

It is important to consider the two main categories of NGS with regards to read length. Illumina define it as:

Read length refers to the number of base pairs (bp) sequenced from a DNA fragment.

With this, there are two types of read length, known as ‘long-read’ and ‘short-read’. For the past two decades, short read has completely dominated – mainly by Illumina themselves. As the more cost-effective and accurate process, short-read sequencing is also favoured for its ability to be widely supported by most analysis tools and pipelines.

Despite this, the other group of technologies, known as long-read, has gradually progressed as a more favourable approach in recent years. Due to capabilities such as improved de novo assembly, mapping certainty, transcript isoform identification, and detection of structural variants, long-read sequencing eliminates amplification bias while preserving base modifications. This ability to sequence native molecules, both DNA and RNA, means long-read sequencing is soon becoming an option for genomic applications in both model and non-model organisms.

Thanks to Pacific Biosciences and Oxford Nanopore technologies, long-read has emerged as the gold standard for microbial, plant and animal research, but it is now moving swiftly into the world of transcriptomics. Oxford Nanopore’s technology has the ability to read up to 1 million base pairs, a huge advantage when conducting de novo assembly.

Incoming change…

When looking to the future of the market, both Illumina and short-read hold a huge market share. However, a few of Illumina’s key patents, developed by Solexa, are due to expire in 2023/2024, leaving a gaping hole for competitors to fill.

An example being MGI. In 2020, Illumina successfully prevented MGI from selling its systems in the US due to infringements to its patents, again developed by Solexa. Despite this, the company continued to trade successfully in China, and now claims it can deliver the $100 genome – which sees the possibility of MGI grasping a hold on wider global markets outside of China too.

Alongside MGI, there have been several other developments in the short-read field, with some very promising start-ups making huge headway. Singular Genomics went public in June 2021, listing on NASDAQ, raising approximately $258 million in gross proceeds. Committing to the development of genomic tools and technologies through vast transformations, increasing speed and power while lowering costs and expanding access to the technology.

Another new player in the short-read market is Element Biosciences, which raised a staggering $276m in Series C financing, intended to fund the launch of the company’s next-generation DNA sequencing platform, whilst scaling its commercial operation. Whether these are intrinsically connected to Illumina’s expiring IP remains to be seen, however it is clear the market is open and willing to see new players thrive in the short-read space.

What could this mean?

As competition increases, as does demand, seeing prices drop and margins tighten. New customers should be thrilled with more choice, whilst opportunities arise for newer companies to undercut current market leaders. Illumina’s acquisition of GRAIL, whose ‘Galleri’ blood test detects up to 50 different cancers at the pre-symptomatic stage, shows the increased interest in downstream applications of NGS. A move which could trigger wide-scale adoption of this life-saving test worldwide.

For existing customers, however, this market progression brings as many obstacles as opportunities. Investing in new systems is no small, or affordable, feat, and training users with new processes is an equally mammoth and expensive task.

Alongside these market progressions, other organisations are developing technologies which can optimise current platforms, replacing the need to invest in new systems.

For example, Cambridge Epigenetix’s recent $88m Series D funding announcement is aimed at revolutionising sequencing by delivering more information from DNA, using the funds to commercialise its technology. Professor Sir Shankar Balasubramanian, said:

[To ensure it] easily integrates into existing sequencing platforms.

Alongside this, the likes of (aptly named) Longas Technologies continue work developing a technology which could turn short-read into long-read sequences with proprietary chemistry and algorithms.

What’s next?

If the failed Illumina/Pacbio acquisition showed us anything, it was that preparation for investment in the long-read space should not be overlooked. It would not surprise me is this failed attempt rears its head again in coming years as the technology is improved.

Alongside this, Oxford Nanopore’s recent IPO indicates the long-read approach to be a market gaining momentum. Despite initial queries, long-read is showcasing itself as the go-to tech opportunity for the most challenging genome regions, allowing a full spectrum of human genetic variation. With these benefits and the depth of information available, it’s sure fire that researchers will begin heading towards long-read providers sooner rather than later.

COVID put NGS under the microscope and prompted a crash course for those who were previously unaware of the term ‘sequencing’. Illumina’s market dominance is likely at risk, and consumer focussed genomics is in closer reach than ever before. As the spotlight shines on NGS, new players emerge and wider market wanes – teeing up the next few years to be some of the best the industry has ever seen.

Are you interested in discussing the NGS and genomics market in some more depth? I’d love to hear from you. Drop me a message at george.coe@lifesci-cm.com.

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George Coe

George Coe works across genomics and cellular biology, partnering with companies and candidates who are at the very forefront of research today. He is fascinated by the way in which genomics is going to affect our everyday lives and the growing regulations surrounding the technology.

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