18 April 2013

X-Gen 2013

I recently had the pleasure of attending X-Gen (more formally known as ‘X-Gen Congress & Expo). This meeting falls on the small side of the spectrum, with a couple hundred attendees, and that suits me just fine. I prefer smaller meetings as I find it easier to network and generally keep track of what’s going on. It does, however, have parallel tracks – RNA Sequencing, DNA Sequencing and Data Analysis – so hard choices sometimes had to be made (e.g., a talk on Illumina’s Moleculo technology or one on duplex sequencing for rare mutation detection; Moleculo won out, but I really wanted to be at both). I’m not quick enough for live blogging – I can type up notes/thoughts, or I can listen, but I can’t do both. Therefore, I’ll just mention some of the things that stuck out in my mind.

  • From Peter Park’s talk on the role of retrotransposition in cancer – 45% of the human genome is derived from transposable elements (most of which are under epigenetic suppression). This isn’t a new discovery, but I still find it fascinating. Same way I find it fascinating every time I hear about how our bodies harbor ~100 trillion microbial cells (dwarfing our ‘own’ 10 trillion cells). Anyway, this analysis is fairly tricky (presumably due to the difficulty of sequencing/aligning repeats), but longer reads on the horizon, like that of the Moleculo technology, should help.
  • John Stam discussed the role of gene regulation in common disease. He mentioned something that, while it intuitively makes sense, I still found really interesting. When he piled up the results from 50 separate transcription factor ChIP-Seq experiments, it matched the results from his DNaseI hypersensitive site ChIP-Seq almost perfectly. Genomic regions available for TF binding would need to be accessible and, therefore, hypersensitive to DNaseI, but it’s still kind of cool to see the results overlap so well. The other interesting thing he showed was that when he had very deep sequencing in a TF ChIP-Seq experiment, the resolution of the binding sites became so good that it matched with the predicted sites of the TF crystal structure. Seeing two completely orthogonal approaches match so closely is pretty amazing.
  • David Smith talked about studying head and neck cancers, first with RNA-Seq and more recently looking at very large genes and chromosome breaks. For example, the FHIT gene at 1.5 million bases is so large that transcription takes so long that it can interfere with replication (hence the breaks). While it isn’t directly related to the science he was discussing, Dr. Smith revealed an interesting marketing tactic (one of the worse kept secrets in the business) about Life Technologies: “SOLiD gave us $300k worth of free sequencing… back in the days with sequencing companies were willing to seduce you.” Very important to keep in mind when companies throw around market share numbers.
  • Cynthia Burrows is using an alpha hemolysin-based nanopore system from Electronic BioSciences (EB) to look at DNA damage and other modifications. EB is one of the nanopore companies flying under the radar. They use a small aperture capillary with a single nanopore and a dual electronic system so that translocation and measurements can be kept separate. Check out the EB entry in BlueSEQ’s ‘Emerging Technologies’ section. Her fun fact for the day is that there are ~10k spontaneous depurinations per genome in a cell per day. That definitely makes me feel like I’m falling apart!
  • Aleksei Akimentiev gave a really interesting talk on solid state nanopores. While he didn’t have any experimental data to show, he showed some fantastic model simulations run on the ‘Blue Waters’ super computer. He has modeled all sorts of nanopores, including graphene layers which turn out to be quite ‘sticky’. He’s working with both Oxford Nanopore [http://blueseq.com/knowledgebank/emerging-technologies/oxford-nanopore-technologies/] and IBM [http://blueseq.com/knowledgebank/emerging-technologies/ibmroche454/]. Check out some of his animations here:
  • Jingyue Ju is working with tagged nucleotides (with various PEG molecules acting as the tags, if I remember correctly). The DNA strand to be sequenced is processed by a polymerase which releases the tags as the nucleotides are incorporated. These tags are what are read by the nanopore. Genia announced last fall that they had switched their chemistry to use Dr. Ju’s system. When asked how long until he could sequence DNA, Dr. Ju answered “In a couple of months we’ll demonstrate real sequencing data”. Good news for Genia?
  • Massimiliano di Ventra talked about “Fast DNA Sequencing via Tunneling” – not exactly a nanopore, but definitely related. It looks a really cool technology, but unfortunately all he has to show at the moment is simulated data. Perhaps the most interesting thing is that he brought a new commercial sequencing company to my attention – he’s been working with Osaka-based Quantum Biosystems (a new one we’ll need to add to the ‘Emerging Technologies’ section of BlueSEQ’s Knowledge Bank.