Next generation sequencing (NGS) is the collective name for a group of amazingly fast and relative inexpensive techniques for reading DNA codes from living and dead organisms. Front-runners in this market must continually move forward because the technology is developing at amazing speed and the lifecycle of equipment is short. This makes it advantageous for institutions and companies to share research facilities, as experienced by Wageningen University & Research and BaseClear.
Bas Reichert is CEO of BaseClear, the genomics company in Leiden that maps the DNA of ‘everything that lives’. “We have a strong focus on small organisms such as bacteria, fungi and algae,” Reichert explains. “These micro-organisms are widely used in fermentation processes for making products such as yoghurt and cheese. Additionally, we do extensive research into the microbiome: the bacterial populations in environments such as the intestines and skin, and in the soil around plants. We work for numerous international clients, from dairy companies to academic research centres and from plant breeders to biotech companies.”
While BaseClear focuses primarily on research into micro-organisms, bio-scientist Elio Schijlen and his research group (Bioscience) at Wageningen University & Research map out the complete, complex genomes of plants. Plant breeders can use the resulting knowledge to develop new crop lines faster, to name just one example. “We are complementary to BaseClear in the field of NGS,” says Schijlen. “What we have in common is that we are both at the forefront of technological development. To maintain this leading position, you have to continuously improve your results, which is not possible with old equipment. And in our line of work, equipment become ‘old’ rather quickly.”
The rapid pace of technological progress creates a dilemma for both partners. Reichert: “You have to invest in new facilities, but at the same time you have to make choices, because NGS equipment is costly. For us it would mean that we would have to make a choice for a single machine, which would also limit us to one type of research. But the market offers space for a more diverse research portfolio, and we want to use that space.”
The solution turned out to be simple: collaboration. Under the name ‘WUR, Shared Research Facilities’, companies and researchers can share the high-tech equipment and facilities on the Wageningen Campus and its vicinity. This collaboration involves research in various fields, including NGS. Daniëlla Stijnen, account manager of Shared Research Facilities: “Shared Research Facilities was established because the Ministry of Economic Affairs & Climate Policy and the province of Gelderland wanted to stimulate sharing of state-of-the-art research facilities as much as possible, and provided funding for this purpose. Sharing facilities offers many advantages to companies, such as lower costs and access to the latest equipment. Moreover, available capacity is used much more efficiently, and users only pay for the hours that they use the machine instead of having to pay for the whole investment and exploitation. We share the costs with users and partners. BaseClear is one of our partners with whom we share NGS equipment.”
In Wageningen and Leiden
The PacBio-Sequel, the NGS machine invested by Shared Research Facilities and used by BaseClear, WUR and others, is located on Wageningen Campus. BaseClear arranged the financing for the NovaSeq itself and keeps the machine at its lab in Leiden. Because the collaboration with the Bioscience research group of WUR was so successful, the partners are also sharing this machine. Elio Schijlen explains: “DNA mapping is done in small pieces. With the machine in Wageningen we map large fragments of a single DNA strand; it is ideally suited for de novo applications, where you want to map a genome from scratch. With the system in Leiden we can map small sequences from a great many organisms at once. Both systems have their advantages and disadvantages, but the combination is extremely interesting.”
The collaboration has gone smoothly, says Schijlen. “We usually announce in an email that we are preparing and processing samples, after which we reserve time to use the machine.” Reichert adds: “Of course, good contractual agreements have been made about aspects such as data security. Our company aims to comply with Good Laboratory Practice (GLP) regulations, which require clear agreements on data use and access to systems. These aspects have also been addressed in the contracts. But the most important thing is complete trust between the partners. Without trust, the collaboration won’t work.”
The competition is also moving quickly
Sharing facilities is crucial for BaseClear to survive in a highly competitive market. Reichert: “Our competitors from countries such as China and South Korea are also advancing quickly. As Dutch players in this marketplace, we will fall behind if we are limited to the machines in our respective labs. Thanks to the collaboration with Wageningen University & Research, we can offer our customers a wider range of products than would be possible with just our own research facilities. This makes us more attractive to customers and strengthens our position in the market.”
For Wageningen researchers involved with sequencing work, it is now possible to do their analyses on the NovaSeq machine in Leiden. Thanks to the collaboration with BaseClear, Wageningen researchers have an additional facility that makes highly advanced analyses possible, in addition to the analyses carried out in Wageningen.
In short: does sharing research facilities offer benefits? Schijlen and Reichert agree wholeheartedly: “Even though you don’t have the latest equipment in your own lab, it is still available to you through collaboration. That provides a competitive advantage to both the research institution and the company.”
The NovaSeq 6000 is the newest workhorse from the Illumina stable. It is an unprecedented production machine that can generate up to 4 Terabases of output per run and thus has enough capacity to read the genomes of 50 people at once. This machine reads a maximum of 2 x 250 base pairs of billions of DNA molecules in parallel. This makes the NovaSeq suitable for re-sequencing applications, providing sequence depth with de novo genomes and producing many data points for applications such as transcriptome analysis. The reliability of the data is extremely high. As a result, this machine is also frequently used for diagnostic applications. Although the costs per run are relatively high, the enormous output means that the costs per data point are very low, which makes it a good machine for labs with large numbers of samples.
The Sequel is the second machine from PacBio. PacBio developed the first single molecule real time (SMRT) sequencing machine for analysis of long DNA molecules. The PacBio Sequel reads tens of kilobases per molecule, resulting in 10 to 50 Gigabases of output obtained from about half a million DNA molecules that are read in real time in parallel. Generating these long DNA reads makes this technology especially powerful for de novo reconstruction of large, complex genomes. Isolating the long and fragile DNA molecules and preparing them for sequencing requires specialised expertise and skills. The long read sequencing provided by PacBio is considerably more expensive per data point compared to the NovaSeq, but these technologies are very complementary when addressing many DNA-based research questions.