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OGT Complements Array Services with Targeted Next-Generation Sequencing

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By Justin Petrone

Oxford Gene Technology this week expanded its Genefficiency genomic services to offer targeted next-generation sequencing.

Under the expanded service offering, the Oxford, UK-based firm will perform whole-exome sequencing, as well as custom targeted sequencing of any genomic region of interest.

Gareth Thomson, director of genomic services at OGT, told BioArray News that the company decided to add the new service to meet demand from customers who are looking to follow up large, array-based studies with focused, follow-on sequencing experiments.

OGT's genomic services customers "typically focus on disease association studies, with a diverse array of follow-on studies in psychiatric disorders, diabetes, breast cancers, and other major complex diseases," Thomson said this week.

"Customers are also beginning to look more at studying multiple biomarkers in their samples," such as methylation and microRNA signatures, he said. Because of this, "many, if not all" of OGT's current customer base is "also looking towards follow-on sequencing-based studies."

OGT has developed a "core service" on the Illumina HiSeq 2000 instrument, although it can also offer sequencing on other platforms, Thomson said. Initially, OGT offers Agilent SureSelect sequence capture for exome and custom libraries. Going forward, the firm will "further evaluate and implement" additional capture methodologies based on customer requirements, he added.

OGT prefers to perform in-solution capture to on-array capture, Thomson noted. "There are several technical advantages to an in-solution hybridization method," he said, such as smaller DNA sample requirements and the ability to capture larger regions with a single design. Also, the kinetics of hybridization is "more favorable for an in-solution method," Thomson claimed.

OGT hopes to win customers who are wary of bringing rapidly evolving sequencing technology in house.

"As sequencing technology develops rapidly, platform choice becomes more risky for individual labs," said Thomson. "By offering access to a wide range of platforms, OGT can de-risk the process of having to select and purchase a sequencing platform," he said.

The addition of next-generation sequencing to its menu follows a series of moves by OGT in recent years to broaden its core business. Founded on the patent estate of Edwin Southern in 1995, the company has in the past decade expanded to offer not only oligonucleotide array-based products and services, but protein arrays, biomarker discovery, and single-cell analysis (BAN 3/17/2009).

The company has also introduced genomic services, branded as Genefficiency, and developed the infrastructure to handle high-volume studies, such as a 20,000-sample project that it conducted for the Wellcome Trust Case Control Consortium in 2009 (BAN 6/2/2009), and the more recent University of Virginia-led 10,000 sample type 1 diabetes study (BAN 11/30/2010). Because of its capabilities, Agilent Technologies named OGT as its first "high-throughput service provider" last year (BAN 3/2/2010).

'Insurmountable Challenge'

Thomson noted that OGT's microarray resources, such as its bioinformatics, probe-design expertise, and laboratory information=-management systems, offer a number of advantages for customers looking to perform target-capture sequencing studies.

In order to offer the service, Thomson said that OGT made a "major investment" in IT infrastructure, R&D, and hired new bioinformatics and laboratory-based personnel. He did not elaborate.

The company has built the service on its "array and experimental design expertise in sample preparation and processing, array design, and interpretation of complex data sets," Thomson said.

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OGT's array probe design capabilities enable the firm to design custom baits to capture genomic regions for sequencing that "achieve highly efficient and uniformly distributed target capture," he said.

"We are expert at using the design tools as we use them every day," he noted. "Designing capture baits [can be] complex and time consuming, so we perform the entire design, order the baits, and perform the capture for the customer."

In terms of bioinformatics, he said that OGT customers are faced with the "insurmountable challenge" of dealing with large volumes of sequencing data, where "one exome can yield up to 8 gigabases of data."

To meet this challenge, OGT said its in-house bioinformatics team will perform "all the standard alignment and quality-control processing that maximizes data quality," as well as "additional intelligent filtering of the information."

OGT's offering provides results in an HTML report that "places features such as insertions, deletions, and SNPs into context," including the identification of affected genes and proteins, possible disease associations, and links to external databases, the firm said in the statement.

In terms of LIMS, OGT has built upon its existing high-throughput system to integrate sequencing studies so that it "tracks every sample through the whole sample preparation, capture, and library preparation process," said Thomson.

"As soon as the sample arrives, it undergoes rigorous [quality control] checks," all of which are recorded. "We then continue to check every stage of the capture and library generation process through additional QC steps," Thomson said.

Choice of Approach

Though OGT is keen to see customers take advantage of its sequencing services, it does not expect its existing array users to migrate wholesale to the newer technology.

"We see NGS and microarray technologies as complementary rather than competing technologies," Thomson said. He said that the choice of which approach to use is largely up to the biological question being asked.

For example, microarrays enable parallel and cost effective analysis of large numbers of samples, Thomson said. "So if the requirement is to screen a large number of samples to analyze a particular subset of genes or genomic regions that are already known for more comprehensive understanding, then microarrays will be more effective," he said.

If the goal is discovery, on the other hand, "then sequencing could be used to identify novel sequence variants," that could later be used to generate new arrays for screening.

Thomson added that OGT envisages arrays, rather than sequencers, "playing a major role for some time to come" in areas like frontline clinical testing.


Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.

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