2015: A Look Back
People are starting to talk about their plans for New Year’s Eve, confirming a suspicion we’ve had for a while now: 2015 really is winding down! We can’t believe that 2016 is nearly upon us. As we try to remember the blur of the last 12 months, we’re taking stock of the highlights and trends that transpired. Here on the home front, the big news was how well our newest instrument, PippinHT, has done. Our customers have run tens of thousands of samples with PippinHT so far, and they show no signs of easing up.
Early this year, we put forth our theory that 2015 would be remembered as the year of long reads. With the momentum of Oxford Nanopore technology and the much-anticipated release of PacBio’s new Sequel System, it seems clear that long-read sequencing is no longer a niche approach. Numerous studies have shown that long-range DNA information is essential to building more accurate and complete genome assemblies, providing insight that isn’t available from other sequencing methods. Even researchers who haven’t switched to long-read sequencers are trying to incorporate long-range data into their studies; we’ve seen a lot more interest in mate-pair sequencing, as well as synthetic long-read technologies.
In 2015 we sponsored our first-ever podcasts with Mendelspod, and they’ve been a huge success. If you missed any of these great interviews with Bobby Sebra, Chris Mason, or Rod Wing, you should definitely spend your next commute tuning in. Mendelspod host Theral Timpson always does a good job of getting his interviewees to provide really interesting perspectives on trends in the industry.
As usual, the Sage Science team spent a good deal of time on the conference circuit this year. We loved getting to interact with friends, collaborators, and customers, and look forward to doing more of the same next year. You can catch our coverage of some of the big meetings here: ABRF, AGBT, ASHG, ASM, Festival of Genomics, and PAG. We also recapped our experience at the PacBio user group meetings here and here.
One of our favorite developments of the year was the publication of some great new protocols involving Pippin automated DNA size selection instruments from our customers. We particularly liked new mate-pair sequencing protocols (here and here), and this video protocol for methylation mapping.
Of course, Sage customers publish a lot more than protocols. There were too many terrific papers to list here, but if you have time for only a few, here’s what we recommend:
– A better approach to microRNA biomarker discovery
– A diploid human genome assembly
– Targeted capture and sequencing of human structural variation
We even got to spend some time profiling a few of our customers this year. Many thanks again to our customers for taking the time, and we hope you enjoy these glimpses of their impressive work:
– Amanda Chilaka, Whitehead Institute
– Darren Heavens, The Genome Analysis Centre
– Alex Maslov, Albert Einstein College of Medicine
And that’s a wrap for 2015! From everyone at Sage, we wish you a wonderful holiday season, and a happy and healthy new year.
Sage Survey Results: Who Won the Apple Watch?
A few weeks ago we asked people to participate in a quick survey to help us make sure that our product development efforts are focused on areas of greatest need to the community. We were blown away by the response — many thanks to all of you who took time out of your busy days to offer your perspective.
We wanted to share a little bit about what we heard. Most respondents work in research, though a fair number came from the clinical realm. The most common genomics applications they use are RNA-seq, targeted sequencing, genome resequencing, and de novo genome sequencing. The single biggest sample prep challenge they reported was dealing with low-input or precious samples. While the vast majority of respondents use short-read sequencers, they expressed a lot of interest in adding long-read sequencing or synthetic long-read data to their pipelines.
We also offered participants the chance to win an Apple Watch. We printed out the list of respondents who asked to enter the drawing, and then we chose Tanja, the cheeriest member of the Sage team, to select our winner (as you can see, she had a good time!). Congratulations to Davinder Sandhu at Weill Cornell Medical College for winning the watch!
Long Reads in All Their Glory: PacBio, ONT User Meetings Report Coming Advances
A pair of user group meetings last week offered some intriguing glimpses into the future of long-read sequencing. Oxford Nanopore customers got together in New York, while PacBio users assembled in Palo Alto, Calif. The Sage Science team attended and sponsored the PacBio event, and we followed the ONT meeting on Twitter and through this great post from Keith Robison at his Omics! Omics! blog.
One of the first things we learned about long-read sequencing when it became available a few years ago is that size selection is perhaps even more important for this technology as it is for short-read sequencers. Removing shorter fragments during library construction allows these sequencers to focus on the longest fragments, maximizing the read lengths generated during sequencing. “ONT has started using the Sage BluePippin instrument to enrich libraries for long reads,” Robison reported, noting that some groups have demonstrated MinION library prep workflows that enrich for reads of 20 Kb and greater. Meanwhile, at the PacBio meeting, CSO Jonas Korlach told attendees about a protocol for building 30 Kb+ libraries using BluePippin for size selection and Diagenode for shearing.
Naturally, the sequencing community is most interested in what’s next for these technologies. According to Robison, Oxford Nanopore told users that they can expect to see direct RNA-seq, amplification-free barcoding, and a higher number of barcodes to allow for increased pooling of PCR amplicons and other samples. Its next instrument, the PromethION, is slated for release to early-access sites in the beginning of 2016; it may generate terabases of data in a single day.
At the PacBio meeting, Korlach spoke about several advances coming to SMRT Sequencing users, who are by all accounts champing at the bit for access to the company’s new Sequel instrument. Attendees were particularly excited about non-amplification-based target enrichment with Cas9, new protocols for HLA and 16S, and the ability to work with low-input samples.
Long-read sequencing is proving to be transformative for the genomics field, where it is chewing through genomes that make other sequencers choke. We enjoy these user meetings for the great science presented, including any number of people reporting the first-ever glimpses of novel architecture, genes, and other previously intractable genomic regions. It was a thrill to hear that PacBio users have now published more than 1,000 papers — truly a milestone for long-read sequencing.
Check out the tweet history for both meetings using #PBUGM and #MCMNewYork15.
Mate-Pair Sequencing Is Having a Moment
Have you been noticing the mate-pair trend? We certainly have. A technique that was once only used by a handful of labs has really come into its own as one of the preferred ways of gathering longer-range genomic data.
Here at Sage, what we like most about mate-pair sequencing is that it’s a clever way of gleaning new information that provides incredible downstream value, making assemblies significantly better. These long-range glimpses of an organism’s genome are enabling more accurate views of biology.
We’ve heard a lot about mate-pair sequencing at conferences we’ve attended recently. For instance, the new Revolocity system from Complete Genomics that was on display at ASHG uses mate-pair assembly to improve results. A recent publication from Lucigen scientists used mate-pair sequencing to improve assembly quality for an anaerobic bacterium cultured from a boiling spring.
Sage customers have been doing a lot of great work with mate-pair sequencing as well. At The Genome Analysis Centre, scientists developed a mate-pair method using SageELF that allows for lower-input samples while saving time and money. That method was essential for the new, highly contiguous wheat genome assembly the centre just released, where it helped boost contig N50 by a factor of 10. At RIKEN, researchers modified a Nextera mate-pair protocol to reduce costs. By using BluePippin earlier in the protocol, they were able to increase yield; they also reduced enzyme volumes for other steps and got high-quality results. In this app note, scientists from the University of Miyazaki also use BluePippin with Nextera for a mate-pair pipeline.
To learn more about how Sage customers are using and improving mate-pair sequencing, check out this page.
Fired Up for This Week’s Festival of Genomics
This week we’re heading to the Festival of Genomics in San Mateo, Calif. We had a blast at the first festival in Boston, so we’re excited about this next edition (and we packed our running shoes, just in case).
The meeting has an impressive slate of speakers — it’s a virtual Who’s Who of the genomics community. If you happened to miss Ting Wu’s mind-blowing plenary talk at the Boston festival, we’re thrilled to see that she’s speaking again and heartily recommend checking it out. The concurrent sessions are chock-full of great talks too, and it’ll be tough to choose among them.
The Sage Science team will be in the exhibit hall, central to all of the presentation stages, and we hope you’ll stop by to say hello. At the June festival, we presented a sneak peek of our HLS system, currently under development. If you missed it, we’ll be happy to get you up to speed on a new product we think will be incredibly useful for the NGS community.
Hope to see you in San Mateo!