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Move Over, GA: Illumina's HiSeq 2000 Increases Output to 200 Gb Per Run

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By Julia Karow

Illumina said this week that it will launch a new high-throughput sequencing platform, called HiSeq 2000, next month that will provide up to 200 gigabases of sequence data and up to two billion paired-end reads on a billion templates per run.

Priced at $690,000, the system will use the same cluster amplification sample prep and sequencing-by-synthesis chemistry as the Genome Analyzer but will run two flow cells instead of one and use a dual-surface imaging method.

One of the first customers of the new instrument, which Illumina plans to start shipping in "limited quantities to selected sites" next month and more broadly in March, is the Beijing Genomics Institute, which will receive 128 HiSeq 2000 machines over the coming year (see other story, this issue).

Illumina will continue to sell and support the GAIIx, and will continue to improve that system's output. An Illumina spokesperson told In Sequence that "we will shortly be broadly releasing improvements on [the] GAIIx that will enable up to 50 Gb of quality data with 100 bp [paired-end] reads, and we are making great progress internally towards our stated goal of 95 Gb on the GAIIx." Originally, Illumina had planned to reach that goal by the end of 2009.

Current GA customers will not be able to physically upgrade their system to the HiSeq 2000, because it is a new type of instrument, but Illumina has a trade-in program in place for GA customers who wish to acquire the HiSeq 2000, according to the spokesperson.

Like the GA, HiSeq 2000 uses the cBot for cluster generation — with an adaptor plate to accommodate its larger flow cells — though it is not compatible with the old cluster station. While the sample and library prep is the same for both platforms, HiSeq 2000 uses its own consumables kits. Data processing and analysis are similar for both instruments.

At launch, HiSeq 2000 will be able to generate up to 200 gigabases of quality-filtered sequence data per run at comparable accuracy to the GA. The initial read length will be up to 2 x 100 base pairs, and the instrument will provide up to a billion single-end reads and up to two billion paired-end reads. A run will take seven to eight days, and users will be able to run the instrument with one or two flow cells. Users can also run applications that require different read lengths simultaneously. Like the GA, each flow cell of the HiSeq 2000 has eight channels.

IlluminaHiSeq2000.jpgAccording to Illumina, initiating a run on the HiSeq 2000 requires less than 10 minutes of hands-on time. In addition, the system offers 96-sample parallel processing for library preparation, thus reducing hands-on time and overall cost.

For comparison, according to the most recent specifications for the GA on Illumina's website — current as of mid-October 2009 — that platform offers read lengths up to 2 x 100 base pairs and more than 300 million single-end reads per run, resulting in up to 33 gigabases of data per run. Preparing a sample takes about 10 hours, followed by a 10-day sequencing run for 2 x 100 base pair reads.

Regarding cost, Illumina said that on the HiSeq 2000 it will cost $10,000 per genome to sequence two human genomes at 30-fold coverage in a single run. Also, for less than $200 per sample, users can analyze gene expression in up to 200 samples per two-day run.

Illumina said that "in particular, the system offers significant benefits for gene expression and epigenetic profiling compared to microarrays," enabling researchers to "generate richer transcript profiles with cost and throughput comparable to microarrays."

With the HiSeq 2000, Illumina is adopting the concept of two flow cells that other sequencing platforms — such as the Applied Biosystems SOLiD or the Helicos Genetic Analysis System — have featured from their inception.

According to those companies' latest spec sheets, the SOLiD 3 Plus currently provides up to 60 gigabases of data in a 12- to 14-day run, and up to a billion sequence tags per run; and the Helicos platform generates 21 to 28 gigabases of data in eight days, and routinely analyzes 600 to 800 million usable strands per run.

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