Up at 5AM: The 5AM Solutions Blog

Next Generation Sequencing Gets Agile: Notes From AGBT

Posted on Wed, Feb 09, 2011 @ 01:18 PM

I had the pleasure of attending my first Advances in Genome Biology and Technology (AGBT) meeting last week on Marco Island, Florida. This blog post’s title is how I, as a bioinformatician, would sum up the meeting although other candidate titles might be “the sequencing platform I bought last week is already yesterday’s donuts”, “to tweet or not to tweet” or “I narrowly escaped the snow storm and now my colleagues back home hate me”.

So what do I mean by Agile next generation sequencing (NGS)? First, note the big-“A” – that’s intentional as I’m referring to the Agile software development process. This is something near and dear to our hearts here at 5AM and if you haven’t heard of it we've got some great material on our web site. In a nutshell, Agile is a lightweight development method favoring frequent deliveries to the customer, quick response to change driven by motivated and often small teams of stakeholders. Although Agile is a software development methodology, it shouldn’t be much of a stretch to think of the development of molecular biology workflows in the same way. My view of Agile science is a small team of scientists and technicians, forming a hypothesis, conducting an experiment and using the outcomes to direct the next experiment in a transparent and nimble fashion.

Until recently, NGS has not been Agile. If you look at the last few years of sequencing platform development, the main driver bringing us sequencing data faster and cheaper has been the ability to massively multiplex sequencing reactions. The sequencing process in technologies like SOLiD or Illumina (Solexa) actually run slowly – taking sometimes two weeks to finish – but since millions of sequencing reactions are occurring at once the data throughput of these instruments is immense. The library preparation and clean up processes are also lengthy ranging from days to even weeks. Add in the fact that a single run on one of these very expensive instruments will run you several thousand dollars and you end up with long iterations preceded by lengthy planning and followed by even lengthier analyses.

At last year’s AGBT, Pacific Biosciences and Ion Torrent both introduced us to technologies that could transform NGS application development into an Agile process. At that time, though, the instruments were better at generating press releases than sequence data in a customer’s lab. With multiple installations of PacBio RS and Ion Torrent PGMs now in the field, this year’s AGBT marked the first time real data was presented from customers of these “Third Generation” sequencers. Short run times (now hours rather than days), easy prep and cheap reagent costs all make Agile science a possibility. Adding to the agility theme, Illumina announced a competing instrument, the MiSeq, and posters and talks were peppered with new, faster sample preparation systems.

So what can we expect from Agile NGS? For software, Agile development promises shorter time to working software, adaptability to changing requirements and sustained development at a constant pace. With a more agile sequencing platform, I believe we can expect much the same: shorter time to scientific results, the ability to adapt experiments to changing realities in the lab and new findings and smoother workflows for non-production (i.e. genome center) settings. Agile NGS is much better suited for developing diagnostics and new assay technologies and fits more naturally with the process of scientific discovery. Agile NGS will also place pressure on the informatics/analysis side to maintain the same agility lest it become a bottleneck. That’s a challenge we’re looking forward to here at 5AM and we'd love to talk to others who are facing the same issues.

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