It's Halloween, and as is my habit I fired up Saint-Saëns, As death tunes up his violin in a graveyard, the dead residents live again and dance with abandon, until the rooster (oboe) crows in the dawn. In a similar vein, a pre-print on bioRxiv has demonstrated new life in the Helicos single molecule sequencing platform, though while the platform stopped being commercially distributed (and Helicos went bankrupt just under 3 years ago), a scrappy little company called SeqLL has kept up a service business. A new Chinese company called Direct Genomics, with two Helicos founders onboard, plans to commercialize the new version of the technology.
A computational biologist's personal views on new technologies & publications on genomics & proteomics and their impact on drug discovery
Saturday, October 31, 2015
Tuesday, October 27, 2015
BGI Launches the BGISEQ-500
This weekend brought the formal launch of the BGISEQ-500 desktop sequencing instrument from BGI (though deliveries won't begin until early next year). Utilizing the ex-Complete Genomics ligation technology also used in the Revolocity system, the instrument appears to sport a price similar to the Illumina NextSeq but offers throughput somewhere running from a NextSeq up to the low end of a HiSeq. Two flowcells can be run at a time (apparently in sync with each other, unlike QIAGEN's long-delayed machine), with a small and large versions of the flowcells. There's some ambiguity on questions such as the precise read length, though it is very short compared the the typical Illumina offerings. Dale Yuzuki has a nice write-up (complete with a picture next to the box) based on attending the International Congress of Genomics 100 where it was unveiled. One of these days I should wangle my way to that conference -- not only would the genomics be fascinating, but China holds a special allure -- or more specifically, Ailuropoda, for our household.
Wednesday, October 21, 2015
Concepts for Better Sequencer Calibration
Last week's release of the MARC data for the Oxford Nanopore MinION rebooted a train of thought I've had around DNA samples used as standards. Ideally, standards would meet a number of criteria, though some of these may be inherently in conflict and there are issues of practicality. But as a whole, the standards used for molecular technologies are often short of ideals in ways which could be addressed, as I will attempt to argue here. While many of my comments will be placed directly around MinION, many apply to other platforms -- as would solutions I have been contemplating.
Tuesday, October 20, 2015
Dovetail Takes Flight
Back in March I covered the unveiling of Dovetail Genomics' approach to scaffolding genomes via deriving long distance constraints from reconstituted chromatin. This morning the company announced full access to their genome sequencing and scaffolding service. Founder Ed Green and CEO Todd Dickinson chatted with me by phone last night about this launch.
Dovetail's offering is a complete service for sequencing or scaffolding large animal or plant genomes. Users can choose from a menu of service components, which can range from scaffolding an existing short read assembly for around $10K to a complete genome sequencing and scaffolding for around $40K, with a turnaround in either case of 6-8 weeks and scaffold sizes on the order of chromosome arms.
Since the beta program opened in the spring, Dovetail has worked to streamline both their wet lab and informatics protocols as they completed over 45 different customer projects. Of particular note is that the input DNA requirements are down from 5-10 10ug to 1-2ug. However, the Dovetail team agreed with my comment from before that with their current markets, de novo sequencing and structural variant calling on known genomes, input DNA has not been a serious constraint. They do believe they can substantially reduce the requirements further, perhaps to a few hundred nanograms.
While the service offerings can include users supplying their own high molecular weight DNA, Dovetail prefers to perform the extractions in house. The logic here is simpler: results are critically dependent on the size of the input DNA. As a result, Dovetail has spent great effort becoming expert in extracting DNA from a wide variety of different species and sample types, as well as using pulsed-field gel electrophoresis for DNA quality control
Dovetail is currently offering their Chicago technology only as a service, which has obvious advantages. Anyone who has attempted technology transfer will know how difficult it can be to make a process consistently repeatable at multiple sites, not to mention the variances that can easily creep in due to the vagaries of shipping. Aspects of this can be seen in the recently released MARC data for Oxford Nanopore. For users, a pure service offering means no learning curve and no equipment purchases; just turn over some biomass to Dovetail and wait for a high quality genome to be returned.
That doesn't mean kits aren't in on the horizon; Dovetail does plan to offer them at some future point. Also in future plans is expanding the service offerings to include metagenomes and haplotype calling. In the nearer term, a publication describing the scaffolding of a human sample (NA12878) and the American Alligator genome, which Dovetail has discussed in the past, is "well along" the publication pipeline. While the current offering is based on Illumina sequencing technology, Dovetail emphasizes that the technology itself is platform-agnostic. In a similar vein, when asked about how Dovetail differentiates themselves from the growing swarm of long range technologies, including Oxford Nanopore, PacBio Sequel, BioNano Genomics, and the now-launched 10X GemCode, their team praised the field as full of exciting technologies, but emphasized that they offer the ability to scaffold complex genomes very fast with no specialized equipment and no new techniques to learn..
Personally, a pure service offering is very attractive, since that means not having to find internal resources to learn the new technology and then execute on it. I checked with Dovetail, and while I don't have $40K burning a hole in my pocket, if I did I could grab something out of the garden or from the local seafood market, I really could have a complex genome scaffold of my very own in about two months. That's an exciting vision, and perhaps will be a major force in the sunsetting of science's tolerance for highly fragmented draft genomes.
Monday, October 19, 2015
MARC spots the Ox(ford)
Last week's end brought the initial report from MARC, the MinION Analysis and Reference Consortium, detailing a body of experiments intended to benchmark the performance and consistency of the Oxford Nanopore MinION sequencing device. The MARC paper is also the inaugural research article in F1000's new channel for nanopore papers.
Thursday, October 01, 2015
PacBio Sequel: Smaller Box, Bigger Bang
Boy, am I regretting taking a vacation from online due to being engrossed in A Canticle for Leibowitz. Between last night and this morning, my neglect of my Twitter feed meant a colleague tipped me to the new PacBio machine with "what's this Sequel I keep hearing about from PacBio". So a lot of folks had a huge jump and covered it pretty well, including Keith Bradnam, Mick Watson, and James Hadfield. Long rumored, the new instrument costs about half as much (but that's still $350K), takes up much less floor space (and doesn't need any reinforced floors) yet the new flowcells deliver about
6 7 times as many reads than the older ones. WOW!
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