What was the primary experimental, technical or computational factors that led to the rapid decline of genome sequencing cost ?
What was the primary experimental, technical or computational factors that led to the rapid decline of genome sequencing cost ?
I suppose the pivotal moment was the bold decision of ABI (then PE Biosystems) to sequence the human genome on their own using capillary sequencing machines, turning the Human Genome Project into a race. As I understand it this was almost entirely due to the efforts of Hunkapiller and Venter. The Human Genome Project really floundered until this moment. We would still be waiting for a first draft of the human genome today if competition was not a factor, and there would be no incentive to develop the new sequencers that followed. So I would attribute the advances to ego.
I don't totally agree. Even though that might be true for some period, the biggest drop in sequencing costs is essentially due to the emergence of "next generation" high-throughput sequencing technologies. Previous efforts (during the Human Genome Project for example) were more oriented to make Sanger sequencing more efficient (automatisation for example), the throughput per sequencing reaction did not improve much (relatively to the last "revolution"). The emergence of these new technologies is also a (economical) competition that stimulated the innovation.
In terms of NGS, I would attribute the advances, beginning with MPSS, primarily to imaging technology. Fluorescence had been mastered for some time before dyed nucleotides, but I don't think digital cameras had the resolution to see beads until around 2000. I still think the genesis of all this was that board meeting at PE where they said "let's just do it".
I agree with Jeremy on this. I was present at the CSHL Biology of Genomes meeting at the time Venter made his announcement. The shock was deeply felt and did indeed spur the publicly funded project to action. The question asks about the primary experimental, technical or computational factors, but sometimes other forces come into play to put those three into practice and actually be used. The race was one such factor.
I agree with Jeremy and Larry that the initial drive to have more efficient and cheaper sequencing technologies was the HGP and the competition of Craig Venter (glad to hear some insights from people that were actually there). But I still think that, even though they are associated of this willingness to rapidly sequence DNA, the development of some technologies was independent from that event. For example (but I might be wrong, thanks to correct me if so), I don't think (or don't know?) that technologies based on the detection of electric signatures of nucleotide incorporation was planned at the time.
Hi,
to my opinion here are some factors that contributed to decrease sequencing costs (some were already mentioned). Note that not all points can be applied to all technologies.
Some data come from this comparative table of sequencing technologies
Disclaimer: I didn't mention technologies such as Pacific Biosciences or Helicos since I am not familiar/documented with these technologies.
I would say there are a lot of factors that contributed into the declining of the costs, since we are talking of sequencing this would be mostly in the experimental and chemical advancements, and also with the engineering part of things. Computational advances might have helped, but i would define sequencing only on the basis of defining molecular/physical strategies to make the nucleotide identification. It would be hard to quantify each one since they vary across platforms and methodologies. Another factor which is outside of the science realm is the law of offer and demand since the fact that nowadays there are more companies working on this, there is tight competition to bring the next thing in sequencing that scientist would find appealing and invest their money in.
I would say automation. The robotics and workflows to just keep pumping new input into the system. Obviously each subsequent increase in performance of sequencing tech added on--and will keep doing so. But primarily--I'd say automation.
I wonder how many people here ever loaded a sequencing gel...and sat in the back of the lab with a colleague reading off the bases. Good times. And a giant time sink.
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Hi, you may want to have a look at this: http://www.genome.gov/sequencingcosts/
I saw this graph before, now that I looked more closely it seems a bit overly optimistic, especially the right hand side - cost per genome.
I was thinking about founding a company :P.
Equally interesting and informative would be the related economic and social factors.