Pushkarev, D., Neff, N., & Quake, S. (2009). Single-molecule sequencing of an individual human genome Nature Biotechnology DOI: 10.1038/nbt.1561
Stitching together a genome sequence with such short reads is a substantial challenge, especially in regions where the sequence is repetitive - and indeed the technology can only cover 90% of the reference genome compared to 99.9% for a genome recently sequenced to similar depth with Illumina.
"This is the first demonstration that you don't need a genome center to sequence a human genome," Quake said in a statement. "This can now be done in one lab, with one machine, at a modest cost." [GenomeWeb]
Brown, who was formerly with Solexa and Illumina, said it was misleading to compare the three co-authors on the Stanford paper with the 250 or so on the landmark 2008 Illumina publication in Nature on the first African genome, because "that paper was the culmination of eight years work." He noted that an earlier 2008 Helicos publication had more than 20 co-authors to sequence a tiny viral genome.
Excellent summary as always. While this doesn't set the bar so high, neither did 454 when they debuted 2nd-gen sequencing in 2005.
I'm just impressed (and pleased) how far Helicos has come in a short time. Do you remember at AGBT last February, John Todd asked Bill Efcavitch why the HeliScope cost so damn much? Efcavitch replied tersely: "We're still cheaper than the Large Hadron Collider!"
Quake told me over the weekend they already have three cancer genomes sequenced and being analyzed, so we should know soon if they can raise that bar.
Fair point about the debut of 454 (although I'm guessing Helicos is desperately hoping it won't end up matching the historical precedent of 454 too closely, i.e. getting there first before being eclipsed by substantially better technologies).
It will be interesting to see what they get out of the cancer genomes, particularly if they've applied paired-end in those cases - with their current single-end approach they'll miss a lot of the more complex structural rearrangements you get in cancer cells.
I agree that it's good to see the progress that Helicos has made, but I'm still pretty skeptical about the long-term prospects of this platform. As I understand it the optics of the system place some pretty fundamental limits on it, and I suspect the need for architectural changes to support a 900-kilogram machine will put a lot of labs off. We'll see...
Thank you for this fascinating overview.
Some of your readers may be interested to know that the genome of a second cancer patient has now been sequenced by the same Wash U group that did the first. The results were reported in the New England Journal of Medicine August 5.
Oops... the second cancer patient completely slipped my mind. I've added him to the list in the first paragraph - thanks for the reminder!
Nice post. Very comprehensive and critical.
I selected your post as one of my "picks of the week" in molecular biology over at my blog (http://amontenegro.blogspot.com).
One other point about the Helioscope worth noting, though sequencing a typical genome doesn't show it off. The sample prep for Helicos is much simpler and involves no amplification (this was demonstrated in their recent yeast RNA profiling paper). For a lot of applications that's probably not significant, but in those where you either want to analyze a lot of samples or have miniscule amounts of starting material or badly degraded starting material, these could be advantages.
The Heliscope has the ability to sequence small strands of DNA faster
as well as large strands. Smaller strands tend to be more common in
labs anyhow and serve as a means to check progress. Illumina's service
may require sending DNA to their facilities, which will take time. If
the accuracy is not too important (e.g. seeing if a DNA insert was
correctly ligated into a vector or counting the number of tandem repeats), Helicos's machine should perform