tag:blogger.com,1999:blog-36768584.post3832637870244921458..comments2024-03-03T18:49:34.382-05:00Comments on Omics! Omics!: PacBio Enters a Binding Agreement to Acquire Omniome Keith Robisonhttp://www.blogger.com/profile/04765318239070312590noreply@blogger.comBlogger11125tag:blogger.com,1999:blog-36768584.post-27812931534398387712021-10-05T08:15:34.870-04:002021-10-05T08:15:34.870-04:00Plasmonic nanohole arrays - could sound a bit like...Plasmonic nanohole arrays - could sound a bit like the zero mode waveguides PCB is using. Whats the chance they will "just" load the Omniome seq chem onto their existing ZMW arrays and do sequencing? Seems they are anyways adding the fluorescent detection...Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-31173768734621804172021-08-18T04:25:09.674-04:002021-08-18T04:25:09.674-04:00Even when you strip out the Covid sales, nanopore ...Even when you strip out the Covid sales, nanopore had higher revenues from life science research than PacBio in 2020.<br />~$79 million vs ~$90 (£65.5).<br />Seems like PacBio need SRS tech as they are losing the LRS tech battle.<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-40492955419783008572021-08-06T17:58:09.958-04:002021-08-06T17:58:09.958-04:00Cluster gen will introduce errors, but I think at ...Cluster gen will introduce errors, but I think at a much lower rate, for the following reasons:<br />-It uses very different polymerase & cycling conditions than lib prep which are likely higher fidelity (I assume Illumina has optimized for this)<br />-In the cluster gen, you only really care if an error happens in the first couple cycles, since you are taking an average fluorescent measurement over all copied fragments (essentially equivalent of a UMI consensus). So if an error is made in cycle 10 (they aren't really traditional cycles since its isothermal), it such a small fraction of the total signal that you won't ever see it. Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-29517949995376485192021-08-03T16:24:49.171-04:002021-08-03T16:24:49.171-04:00If cfDNA PCR introduces errors then presumably so ...If cfDNA PCR introduces errors then presumably so does cluster generation? Or do the fewer cycles not create this, or is cluster generation non-exponential so not create this??Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-38553687297262471392021-07-29T14:34:35.577-04:002021-07-29T14:34:35.577-04:00I agree with the other comments - methylation is a...I agree with the other comments - methylation is almost certainly out because of the clustering issue. But even if it could be retained after cluster gen, you would be averaging a kinetic measurement over hundreds or thousands of molecules in each well. Even with expensive optics (which seems unlikely if the want to be competitive), I'm not sure this would be possible. Unless of course it can be converted to a 5th base, and no kinetic measurements are needed. In short, I think the kinetic abilities will be lost post cluster gen.<br /><br />A comment about error rate - my understanding for applications like cfDNA is that the errors are largely in the library prep, since any PCR amplification will introduce errors even before the library is loaded on the sequencer. So you can make the sequencer as accurate as you want, but you still need UMIs and oversampling to remove errors from the library prep. The only way I can see to work around this is if you could load tiny amounts of un-amplified DNA into the sequencer. Then you'd need much higher conversion on a flow cell, which is challenging from a cost perspective. Another challenge of course would be amplification-free target capture.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-64651861255423760032021-07-22T02:13:20.836-04:002021-07-22T02:13:20.836-04:00I was about to say we only really find out about t...I was about to say we only really find out about these things when they ship, but even thats not true, what happens in the years subsequently really makes or breaks these genomic platform technologies. It’s a long long road from announcement to reality.<br /><br />Looking at pacbs numbers, they’re not on track yet for the 97% revenue growth promised last year, looking more like 30-40%. This merger ups their running costs in a way that far outstrips growth. With this instrument not due to 2023, and probably not making much initially, pacb looks like its in the debt stripey-hole. Unless of course, more announcements are forthcoming.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-90034522207527262982021-07-21T17:36:56.558-04:002021-07-21T17:36:56.558-04:00This quote from the genomeweb write up gave me a g...This quote from the genomeweb write up gave me a good chuckle.<br /><br />'While the sequencing chemistry is "very far along and very robust," PacBio will work to dial in the clustering to optimize the number of reads per flow cell and will apply its knowledge about enzymology, surface chemistry, dye and optics, and bioinformatics.'<br /><br />Just a few unimportant things to wrap up. It's very robust.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-65507760975659480422021-07-21T11:48:53.947-04:002021-07-21T11:48:53.947-04:00To the two folks who pointed out clonal amplificat...To the two folks who pointed out clonal amplification (clustering) would erase any methylation I can only say:<br /><br />DOH! <br />Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-65603321026473201062021-07-21T10:32:22.205-04:002021-07-21T10:32:22.205-04:00nice write up.
the terminator has to be fantastic...nice write up.<br /><br />the terminator has to be fantastically efficient and pure to stop phasing.<br /><br />if they using labelled nucs then they're using custom pol and they'll have photodamage. does it read on ILMN IP or is it equivalent?<br /><br />cycle times look slow, box will be mid sized to large.<br /><br />clever synergies may take some of the complexities out of making a new box/product lines.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-24139792941809505902021-07-21T02:45:10.911-04:002021-07-21T02:45:10.911-04:00Keith, great post as usual, I do have a couple of ...Keith, great post as usual, I do have a couple of comments though:<br />1- If they need to cluster first (e.g. assuming this is not going to be single molecule), how can they detect methylation (the methylation signal should have been lost during clustering)?<br />2- If the read out is optical, how do they measure kinetics across the whole flow cell (i.e. real time measurement)? The only option would be to use a CMOS flow cell, in which case they may be limited to small flow cells only, given the cost of a large CMOS chip.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-31075067746989826212021-07-21T02:23:13.216-04:002021-07-21T02:23:13.216-04:00I don't see how methyl-C detection can be done...I don't see how methyl-C detection can be done on a clonal system (won't it get wiped out on the amplification?) but interested to know if I'm wrong there.<br />As always with claims of accuracy, I will wait and see what a customer gets. Haven't every next-NGS company oversold on this? Illumina has proved its accuracy for many many years however.Anonymousnoreply@blogger.com