Details and Perspectives as Illumina Announces their Newest DNA Sequencing Machines and the $1,000 Human Genome

INTRODUCTION

A couple of days ago, at the healthcare investment JP Morgan Healthcare Conference, the CEO of Illumina (one of the major DNA sequencing technology companies) announced their newest line sequencing machines.  The two new DNA sequencers are the NextSeq 500 and the HiSeq X10, with the NextSeq 500 being marketed for everyday laboratory use, and the HiSeq X10 being marketed as a factory level, population sequencer (this is the higher power model).  These are going to be powerful, state-of-the-art machines that are going to have a significant impact on both research and clinical applications.  Here I am going to briefly cover what these new machines are and what their release means for contemporary research and clinical applications.  As always, I will also point you in the right direction for further reading, in case you are interested in more.

WHAT ARE THE NEW MACHINES?

So what are these new machines?  To get a good perspective, I am quickly going to go over the existing systems, and then compare them to their newest "replacements".  So far, Illumina's approach has basically been to sell two types of sequencers, with one being a lower throughput, cheaper, "personal" desktop sequencer and the other being a high throughput, high powered, expensive sequencer that is more for the seriously big jobs.  Until now, the smaller desktop sequencer has been the MiSeq platform and the higher powered sequencer has been the HiSeq 2500 platform.  Although it is relatively less powerful when compared to the HiSeq, the MiSeq is capable of sequencing an entire bacterial genome (and other small genomes), is capable of sequencing a human exome, and is also great for many amplicon-based sequencing experiments, such as those that involve the sequencing of 16S rRNA genes.  This machine has read lengths up to 600bp (base pairs) long, can yield up to 50 million reads (paired end), and takes about a day or two to run, depending on chemistry used (more info here).

On the other hand, the more powerful and more expensive HiSeq 2500 system is able to get DNA sequences up to 250bp long (300 bp for the rapid, less throughput chemistry runs), can yield up to 8 billion reads (paired end), and takes up to nearly two weeks (11 days) to run a single set of samples (more info here).  This machine is used for RNA sequencing, DNA sequencing experiments that require incredibly high genomic coverage, or for the sequencing of large genomes like the human genome.  So how do the new machines compare?

The new HiSeq X must be purchased as a set of 10
machines for $1 million each, making the set of ten
(the HiSeq X10) cost $10 million.

According to the Illumina Website, the NexSeq 500 (the newest lower power machine, so it's like a new MiSeq) will be able to get reads up to 300bp long (paired end), can yield up to 800 million reads, and will take less than two days to run.  This means that the NextSeq 500 will yield up to 16 times more reads than its MiSeq predecessor, but still a lot less than the current HiSeq 2500.  Nonetheless, the NextSeq 500 is still a desktop sequencer that will be significantly more powerful than the MiSeq desktop sequencer.  The cost of a NextSeq 500 is $250,000.  Like the NextSeq 500, the HiSeq X10 blows its HiSeq 2500 predecessor out of the water, both in the amount of data it generates, as well as its cost.  The HiSeq X10 will be able to sequence the same amount of DNA about six times faster than the HiSeq 2500, and will be able to sequence about five entire human genomes in a single day with a coverage of 30x (the standard for good genomic coverage).  The HiSeq 2500 is only able to sequence about one entire human genome in a single day.  The HiSeq X10 is expensive and because it is sold as a set of ten machines, it costs $10 million.

PERSPECTIVES ON THE $1,000 HUMAN GENOME

The cost to sequence a human genome has continued to drop since 2001.

Of course the biggest hook of this announcement has been that Illumina is claiming to have made possible, for the first time ever (others have claimed this but failed to deliver), a sequenced human genome for under $1,000.  Now of course this claim comes with a bit of a caveat.  According to Illumina, running a single sample (so a single human genome) will cost about $800 in reagents, so technically a single human genome will cost less than $1,000.  However, these machines are selling for $1 million each, and you have to purchase them in sets of ten, so the machine cost up front will be about $10,000,000.  After you consider the costs associated with preparing the DNA for sequencing, the costs associated with maintaining and running the machines, and the analyses required for the data, it seems like we may be getting out of that $1,000 range.  I have not done the math, so I can't give you a detailed explanation or say exactly what the cost is going to be.  Fortunately another blogger outlined some informed calculations and it looks like the claims may actually be true, and that the cost per genome will be less than $1,000, provided 18,000 genomes are sequenced (see here). In other words, the machines will essentially have to be running constantly for this cost claim to hold up.  But this is getting nit-picky anyways, and the main point is that the cost to sequence a human genome is continuing to plummet and will likely be playing more influential roles in medicine down the road.

So, in the end, what does all of this mean?  Essentially, Illumina once again appears to be leading the pack in affordable human genome sequencing, and we can expect to see more of these kinds of technologies in common medical practice as the costs drop and the technology becomes more accessible.  In addition to making DNA sequencing potentially more accessible to the public, this new technology is going to provide immense power to researchers like me, who can now get even more information for less of a cost.  Furthermore, the efficiency and cost will likely improve database collection (like human genome databases, which can be used for powerful research) which could be performed by governments or corporations.  Overall, this technology is yet another big step forward in genomic research, and this is certainly an exciting time to be a scientist (either professionally or as an amateur).

Want to learn more, or just check the claims I made above?  Check out some of the resources below.

Works Cited & Further Reading

Erika Check Hayden (2014). Is the $1,000 genome for real? Nature DOI: 10.1038/nature.2014.14530

Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L, & Law M. (2012). Comparison of next-generation sequencing systems. J Biomed Biotechnol. DOI: 10.1155/2012/251364

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Sequencing Gel Stock Photo

HiSeq X10 Stock Image

Cost Per Genome Graphic