Network Biology 2.0 part 2

The next talk was by Steve Turner the pacific biosciences founder where he talked about not surprisingly, pacific biosciences 3rd gen sequencing technology SMRT. This was I think my favorite talk. He had a super polished presentation and talk but in addition there was a lot of really awesome stuff in it.

He went through his single molecule technology which uses these things called zero mode wave guides to sequence. They appear to be focusing on laong read length and accuracy. In sequencing the e. coli genome they had an average read length of 586bp with a max read length of over 2000bp. He stated that the main cause of sequencing termination is damage by the lasers which I thought was interesting and said one thing that they were doing was pulsing the laser on and off. Since they circularize the dna strands in their technique this results in the polymerase continuing to sequence the strand over and over again, only actually recording the reading when the pulse was on. I don't entirely understand how this is useful but it seemed to be.

The really awesome thing that he described was how they methylation of a nucleotide causes a recognizable signature. That at this point they are able to identify methylation of base pairs via their SMRT technology and that this same principle can be applied to any sort of base pair modification potentially, although that appears to be a work in progress. I'm not sure if he mentioned or whether it's the case that the SMRT technology requires amplification. So I'm wondering if it does, won't the base pair modifications generally speaking be lost in that step, sort of negating that usefulness.

He additionally mentioned that they were working on a direct RNA sequencer using their SMRT technology. He mentioned it in the context of sequencing viruses but if you could do direct mRNA sequencing with it, and detect their post translational modifications I think that would be an incredibly revolutionary point in gene expression studies.

Direct RNA sequencing while recovering all post translational effects would allow for all kinds of crazy shit like correlating among inter-gene modifications. At this point with RNA-seq you can already do something like this with exons but because of the typically short reads it seems like it could be problematic.

In addition this would potentially exponentially increase the feature space of a transcriptional regulatory network, hopefully the increase in the ability of sequencing technology would allow for it to still be useful, but as it seems all of this stuff is in the next 5? or so years in the future we'll just have to wait and see. Regardless this left me really excited.

He closed with using ribosomes to do translational sequencing which is still not a solved problem for them but represents an amazing opportunity undoubtedly. I was too busy geeking out thinking about the RNA sequencing so I didn't pay attention to this as well as I should.