Today (February 17, 2014) marks the end of the 2014 Advances in Genome Biology and Technology, an annual gathering whose principals include Dr. Eric Green (Director of the National Human Genome Research Institute) and Dr. Elaine Mardis (co-director, with Rick Wilson, of the Washington University Genome Institute). Every year they line up a great roster of engaging and interesting speakers (here’s the agenda for the meeting) and I thought I take a few moments to share some of the highlights from one talk.
I know there are many who want to hear about all the latest technology, and certainly there was a lot of new technology on display that I’ll write about over the next few weeks, including the latest from (in no particular order) Oxford Nanotechnology, Gencell Bio (and their remarkable CLiC™ liquid handler), and Nabsys a single-molecule genomic mapping instrument. (Some others to tease you with are the latest target enrichment from WaferGen, PacBio’s excellent showing with their new C5-P3 chemistry, and other technology such as quantum-tunneling based sequencing and using droplet digital PCR for haplotype phasing – I’m getting ahead of myself though.)
And also on a personal note, many thanks to all those who I’ve gotten to meet in-person as a result of you coming up to me directly. Whether to express appreciation, or astonishment (one memorable person asked me, “Is there anything else you do besides Twitter?!?”), it is at a conference where person-to-person interaction just cannot find a substitute for. Yes video recordings are really useful for accessing great information given in remote locales, and yes social media allows other kinds of interactions in an immediate fashion, but nothing like sitting next to someone you just met at breakfast and hear about some of the problems that they are working on. Or the weather in Branford CT, for that matter. (I’m reminiscing a conversation I had on the way to the RSW airport: it gave me a lot more to ponder about the history of next-generation sequencing, as well as the fact that there are real-world individuals behind the development of all this technology.
On that note one major highlight of #AGBT14 has to be Dr. Jeffrey Schloss‘ plenary talk on Saturday. I had not had heard him present before, and was expecting to hear a lot about the history of the development of NGS, and he certainly did not disappoint. He entitled his talk “Ambitious Goals, Concerted Efforts, Conscientious Collaborations – 10 Years Hence”. Starting with a chart of cost per base’ on the Y-axis (note: not ‘cost per kilobase’ or ‘cost per megabase’ but ‘cost per base’) and the years going from 1990 to 2005, the cost per base went from $10 down to $0.02 over those 15 years, a human genome would still cost on the order of $50M depending on the amount of coverage (and the amount of discount from the vendor of the Sanger sequencing reagents… oh yes, that would be
Applied Biosystems Life Technologies Thermo Fisher Scientific). (By the way that’s some humor there, if I get in trouble for it I’ll be sure to delete it, if you can still access the prior sentence well everything is okay so far.)
Then going through the rationale of the initial RFAs (“Request For Applications”) of the original grants, there certainly wasn’t the time to review every recipient of those first grants in 2004, but Genome.gov has preserved this list, which lists many people and companies that are well familiar – Agencourt (that became the SOLiD technology), 454, and in later years Solexa (that became the Illumina technology), Polonator (George Church of Harvard) and Helicos (now defunct). Several of Jeff’s slides were photos of these systems and lists of companies, some familiar and others not so.
And as an indication of the foresight shown in 2004, microfluidic sample preparation for nucleic acids by Duke researchers that turned into Advanced Liquid Logic, recently acquired by Illumina, as well as several grants supporting efforts around single-molecule sequencing.
On that note he went into a discussion of how long the idea of nanopore sequencing has been in existence – referring to a 1996 Proc Natl Acad Sci paper by Deamer et al (PubMed reference here), entitled “Characterization of individual polynucleotide molecules using a membrane channel”. Of course the advantages of single-molecule sequencing (not necessarily using a nanopore, such as Helicos and Pacific Biosciences) were laid out clearly: directly reading nucleotides simplifying the sample preparation, enabling very long reads, enabling a non-destructive method of interrogation, and the ability to measure non-standard DNA bases (such as 5-methyl cytosine – vital for epigenetic transcriptional control, along with many other modified nucleotides that are present but whose function is poorly characterized due to the inability to easily measure them).
How did this work so successfully? He attributed it to the requirement that grantees share their work, motivated by meetings such as AGBT (to the limit of their commercial obligations), the function of competition as well as collaboration between groups, and the opportunity for students to learn and contribute.
He finished with a peek into the future (quantum tunneling to sequence DNA, anyone?) as well as the NHGRI’s vision of ‘Base Pairs to Bedside’, figure 2 from their 10-year strategic plan published in 2011 (available as a PDF here).
I’ll have more to say about other talks that stood out to me as I get around to reviewing my notes, which frankly is just the ‘stream-of-consciousness’ tweets that I was typing out as the presentations are shared. A few other talks do come to mind, but this one is a good one to start with (in this ‘series’) to give needed historical perspective on where we’ve been in the world of sequencing, and where we could be headed in the future.