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PacBio Books 9 Systems in Q1, Highlights Applications Beyond Bacterial Genome Sequencing

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This article was originally published May 1.

NEW YORK (GenomeWeb) – Pacific Biosciences said last week that it booked orders for nine of its PacBio RS II systems in the first quarter of 2014, up from the four it booked in the first quarter one year ago and matching the nine it booked in the previous quarter.

As a result, the firm brought in total revenues of $11.6 million, more than doubling its first quarter 2013 revenues of $5.1 million. Revenues also included $1.7 million from the company's development agreement with Roche Diagnostics. PacBio provided no further updates on the progress of that collaboration. For complete details on PacBio's financials, see here.

During a conference call discussing its first quarter results, CEO Mike Hunkapiller said that the company is on track to launch previously discussed enhancements to its PacBio RS II sequencing system. Later this year it plans to release sequencing chemistry that will increase average read lengths to more than 10,000 bases, with the longest reads "well above 40,000 bases." Also this year, the company plans to make efficiency improvements to the SMRT cells that will lead to a four-fold increase in throughput. And in the second half of the year, PacBio will release software improvements, Hunkapiller said.

Due to these continuous improvements, Hunkapiller said that the company is "branching out from the niche" of bacterial sequencing and becoming "recognized as being strong" in fields such as plant and animal sequencing, RNA isoform sequencing, and sequencing troublesome regions of the human genome.

Indicative of the firm's shift into applications outside of bacterial whole-genome sequencing, HLA typing firm HistoGenetics recently purchased two PacBio RS II systems. Hunkapiller said that the firm started using one system this quarter and will have its second system up and running later this year.

Complex regions of the human genome

HistoGenetics began exploring the use of next-generation sequencing for HLA typing last year when it purchased 20 of Illumina's MiSeq systems. Illumina said earlier this month that the firm recently bought additional MiSeq systems, giving it the largest fleet of MiSeqs among Illumina's customer base.

According to Hunkapiller, the RS II will offer advantages over the MiSeq, other short read sequencing technology, and traditional HLA typing methods such as Sanger sequencing and probe-based PCR technology, due to its long read lengths that enable users to sequence through the entire HLA gene.

Short read next-gen sequencing technology, Sanger sequencing, and probe-based PCR methods traditionally look at isolated exons, Hunkapiller said. But, "a lot of the key opinion leaders within the HLA community, have realized that what they really need is to look at the entire gene as a whole," he said. "And they can't do that properly with any of the short read sequencing or probing technologies."

He added that PacBio can already demonstrate that "in a production environment, we can do full length Class I HLA sequencing for a lower cost than people can do isolated exons." As such, he said that he anticipates that PacBio will "have a very strong position in the HLA market, both in research, and eventually, the diagnostic world."

The HLA region is only one area of the human genome for which PacBio sequencing offers advantages over other next-gen sequencing technologies, Hunkapiller said. He cited the company's de novo sequencing of the human genome, which generated an assembly with an N50 of 4.38 mb, compared to the most recent reference-guided assembly with Illumina sequencing and BAC-clone finishing with a contig N50 of 144 kb. PacBio discussed this work in February at the Advances in Genome Biology and Technology meeting in Marco Island, Fla.,

Data from that de novo assembly is "already being used to fill in gaps in the human reference genome arising from complex sequence contexts that are refractory to short read sequence analysis," Hunkapiller said.

Although it is now possible to de novo sequence a whole human genome with PacBio technology, Hunkapiller said that the company is not aiming to compete with Illumina in sequencing large numbers of whole human genomes because from a "throughput and a cost perspective" it is not yet there. However, he said that the company is seeing interest from researchers performing whole human genome sequencing with short read sequencing technology that want to "supplement some targeted areas that are missing." While short read sequencing "gives you good data on a portion of the genome," Hunkapiller said, "it leaves out a lot."

For instance, Hunkapiller pointed to isoform sequencing as a growing application of the RS II, citing a publication last month in the Proceedings of the National Academy of Sciences by a group from Stanford University that sequenced the isoforms of a family of genes called neurexins, which are involved in the formation of connections between cells in the human brain. While the genes have been difficult to study in the past due to large numbers of different splice isoforms, using PacBio technology, the researchers "identified hundreds of different neurexin isoforms, highlighting the staggering complexity of these gene families," Hunkapiller said.

Cash crops and livestock

While PacBio sequencing is mainly being applied to human genomics in a targeted fashion, focusing on difficult-to-sequence areas, researchers in the plant and animal space are turning to the technology for de novo sequencing and assembly to create better reference genomes, Hunkapiller said.

Following the Plant and Animal Genomes conference held in San Diego in January, Hunkapiller said the company is "seeing new sequencing projects being started involving important cash crops."

Assemblies of plant and animal genomes from short read sequencing technology "tend to be of pretty poor quality," Hunkapiller said. Given that there is a significant commercial interest in many of the crops that are being sequenced, "having much better assemblies and genome references for breeding purposes is really important."

There are "an enormous number of valuable plant and animal species out there to work on, and we're getting to be much more recognized in that space," he added.

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