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Roche's Upcoming Heat-Seq Target Enrichment Product Promises Automation-Friendly Workflow


NEW YORK (GenomeWeb) – Roche NimbleGen is preparing to launch a new target enrichment product for next-gen sequencing called Heat-Seq that relies on empirically tested molecular inversion probes.

Earlier this month at the Advances in Genome Biology and Technology meeting in Orlando, Florida, Daniel Burgess, director of development at Roche NimbleGen, which is part of Roche Sequencing, a business unit of Roche Diagnostics, provided some details about the new target enrichment product line, which is scheduled to launch in the second quarter.

Molecular inversion probes (MIPs), oligonucleotides where both ends hybridize to a genomic target, forming a circle that can be filled in and amplified, were invented several decades ago and have been used in numerous research projects to amplify target DNA, Burgess explained.

Researchers in George Church's group at Harvard Medical School, for example, published a paper in Nature Methods in 2007 in which they used modified MIPs to target 55,000 exons and detect about 10,000 of them by sequencing.

However, no commercial version of MIPs exists to date, and MIPs are not widely used for several reasons, Burgess said: protocols for their use are difficult to develop, little software exists to analyze MIP data, and the probe design is challenging, with fewer than 90 percent of MIPs typically working from the start. Also, because the efficiency of individual probes differs, MIP libraries require optimization.

Heat-Seq uses an "advanced version" of MIPs, he said, and NimbleGen was able to overcome the probe design challenge using its microarray technology, which allowed it to synthesize and evaluate large numbers of probes prior to selecting them, and to build a large database of probe designs for custom panels.

The workflow for Heat-Seq, which includes library preparation but not sequencing, takes a total of 6.5 hours, including 1.5 hours of hands-on time, and combines several enzymatic steps in a single tube. Roche has developed software for analyzing Heat-Seq enrichment data.

Initially, Roche will launch two fixed-content oncology panels — Heat-Seq Oncology and Heat-Seq Ultra Oncology Hot Spot — as well as customized panels with content for oncology, inherited disease research, and genotyping. The automation-friendly method promises high throughput, making it well suited for projects that involve large numbers of samples, according to the company.

Heat-Seq Oncology covers 60 cancer genes, a total of 240 kilobases of target sequence, and uses 5,144 probes. Heat-Seq Ultra Oncology Hot Spot, on the other hand, comprises hotspot areas in 53 cancer genes, covering 30 kilobases of target sequence with 635 probes.

Customized panels can include up to about 20,000 probes, according to Roche. Inherited disease panels, for example, can incorporate up to 420 genes involved in Mendelian disorders, and oncology panels can include up to 500 cancer-related genes. Also, for genotyping-by-sequencing applications, customers can choose from 76,000 SNPs, covered by 76,000 probes.

Initially, Heat-Seq will only support Illumina sequencing platforms. Pricing for the catalog and custom panels is not available yet but is expected to be competitive with other target enrichment systems, Roche said.