tag:blogger.com,1999:blog-36768584.post2251355655364033387..comments2024-03-03T18:49:34.382-05:00Comments on Omics! Omics!: PacBio's Quixotic Patent LitigationKeith Robisonhttp://www.blogger.com/profile/04765318239070312590noreply@blogger.comBlogger20125tag:blogger.com,1999:blog-36768584.post-73234606438159127522017-03-17T18:36:36.629-04:002017-03-17T18:36:36.629-04:00Better get your patent hat back on:
http://www.li...Better get your patent hat back on:<br /><br />http://www.lifesciencesipreview.com/news/pacific-biosciences-sues-uk-company-over-dna-sequencing-technology-2082<br /><br />I don't profess to be knowledgeable about this area but I don't see how it relates to PacBio's tech though? I hate to say it but it smacks of them just being patent trolls, which is a real shame.<br /><br />Who knows, in their defence I saw Alexander Wittenberg's tweet about the Sequel only managing 5-6 GB and then Nick Loman's tweet almost the next day of a 5 GB Minion run that had 800kb reads in it. That's hard for PacBio to compete with on a science level. Couple that with Roche dumping them then maybe it is a lot worse at PacBio than we all thought?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-46436142273102102562017-02-24T06:22:48.056-05:002017-02-24T06:22:48.056-05:00I'm not a scientist just an investor, but as f...I'm not a scientist just an investor, but as far as I've read through here, everyone has conflicting information so it's all useless info. Talk about alternative facts! I would expect more from the science community.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-35712255126854358382016-12-04T06:24:44.817-05:002016-12-04T06:24:44.817-05:00"That's also probably why ONT are doing t..."That's also probably why ONT are doing their "user conference" now, to increase investor confidence prior to the raise."<br /><br />As i Understand they do two user conferences per year, one in London in May (for the past two years) and one in New York in late November. There have been four so far.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-58149291619741573472016-12-04T06:22:46.003-05:002016-12-04T06:22:46.003-05:00"I've still not even seen 90% overall acc..."I've still not even seen 90% overall accuracy rate properly substantiated. I've seen graphs that show that there's a population of reads, some of which have an accuracy of ~90%. "<br /><br />Distributions of error for all reads, aligned as you say, have been widely published and the data made fully available, they clearly show ~87-93% error for 1D reads and ~97% mean error for all '2D' reads. You could of course buy a MinION and find out for yourself within about an hour of prepping a sample (unless of course you work for PacB so cannot by a MinION).Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-5203605830162977392016-12-02T06:23:09.776-05:002016-12-02T06:23:09.776-05:00They'll say anything to raise another round (w...They'll say anything to raise another round (which they need, check their accounts). Back in 2012 they said they had a 3% error rate (obviously when shipping devices appeared that was not the case). There's probably some truth here but a lot of these statements are driven by what they think their investors want to hear.<br /><br />I've still not even seen 90% overall accuracy rate properly substantiated. I've seen graphs that show that there's a population of reads, some of which have an accuracy of ~90%. But I've not seen anyone take a simple dataset, align it, and then report an overall error rate. If there's a public dataset that does that it would be great to see.<br /><br />Unless I can see that, I'm going to assume accuracy is still around an 80% average (which sucks).Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-40067999112328196162016-12-02T06:11:09.176-05:002016-12-02T06:11:09.176-05:00The minion is not a commercial product, clearly. A...The minion is not a commercial product, clearly. Actually, go look at ONTs latest accounts (available to end the of 2015 on companies house). They recognized 750KGBP in revenue for sales, against a cost of goods of 500KGBP. That's a horribly low markup (Illumina markup is something like x10 cost of goods). But even so, it probably doesn't reflect the true cost. There a whole bunch of places they good be hiding costs just to make it look like the minion is sold at a profit in the accounts (e.g. is the cloud compute included, or is that a "research expense"?).<br /><br />Anyway... as always timing in important. I'd guess PacBio are doing this now because ONT are looking to raise another round in December. That's also probably why ONT are doing their "user conference" now, to increase investor confidence prior to the raise.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-50743488010643604232016-11-07T05:59:41.083-05:002016-11-07T05:59:41.083-05:00Some interesting and salient points in here - I...Some interesting and salient points in here - I've commented beneath each :<br /><br />In response to Dicky<br /><br />1) Pacbio hasn't been on the market for 8 years. They've been on the market only 5 years. But both ONT and Pacbio were founded in 2015. <br /><br />>> I think you mean 2005 ? Actually PacBio claims it was founded much earlier. The RSII went into first shipment in 2010, so its six years old versus ONTs 2.3 years.<br /><br />2) Pacbio went from 1k mean RL and 75k ZMW's to 20k mean RL and 150k ZMW's in 4 years. That's a 40x improvement in throughput. ONT has also been rapidly improving their chem. But a lot of the large throughput numbers are just very long run times >24h. You could take an RS chip and probably do some type of rinse and reuse to also get super long runs with high throughput. <br /><br />>> This is utterly incorrect, their run time has been 48hrs since the MinION came out. ALL of their throughput improvement comes from the speed of translocation of the DNA coupled with having more of the available channels occupied by single pores.<br /><br />3) ONT is still a bit off from being commercially ready. Hand picking a few data points is easy, but having a product that works reliably for thousands of customers will be a big challenge. It took Sequel 1 year to really start performing how it should. It will take ONT a while to adjust from a development product to a commercial product. <br /><br />>> They have 3000 machines out, most or all paid. Id say that was commercial. Sure early technologies have variability.<br /><br />I don't think this lawsuit by Pacbio was done is desperation. It's very likely ONT is infringing on a patent. And it would be stupid for them not to go after it. Don't forget this is corperate America, where companies like Apple will sue over swiping. <br /><br />>> The infringement arguments will come out. It is also useful to use the ITC to kick potential competition.<br /><br /><br />Also being forced to only use 1D reads will be a decent blow to ONT. Even if a 1D ready is in the 90-95% accuracy it still will be lower than the 99%+ by a 2D read.<br /><br />>> True, although throughput doubles with 1D over 2D, even so, accuracy still better than PacBio. They do need to fix the consensus calling of homopolymers.<br /><br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-66133391035516911082016-11-07T05:51:41.833-05:002016-11-07T05:51:41.833-05:00"One thing that must be noted is that because..."One thing that must be noted is that because of the undisputed breakneck rate of improvement in their performance, both PacBio and ONT are rapidly coming up against physical limits of what the measurement technology is capable of. The next wave of improvements will have to come from the biochemistry. And everyone knows (or should know) that any hope for exponential improvements in chemistry is a pipe dream. Our phones would not be stuck at 12 hrs of battery life under moderate usage if that was not the case."<br /><br />As I understand the technology this statement is utterly false. The difference between PacB and ONT is PacB currently rely on advances in third part camera sensor technologies which may not be incentivised to move in their direction. ONT designs and makes its own sensors.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-35555441359849626942016-11-07T05:48:04.450-05:002016-11-07T05:48:04.450-05:00As to this comment :
"As to ONT claiming tha...As to this comment :<br /><br />"As to ONT claiming that they are commercial, not sure how anyone can objectively believe that. Until you can order one without restrictions they will remain in only what can be described as an early access program. Just because they conveniently drop the "early" part of the name does not make it commercial. ONT can go and order a Sequel. ONT will be commercial when PacBio can order a Minion. "<br /><br />Anybody can order a MinION, except a direct competitor - why would a direct competitor order one?. You are wrong - NOT everyone can buy a Sequel because first you have to rustle up 350k dollars. How many post-docs (or anybody) can do that ? Further, whole countries and their relatively poor scientists are excluded from buying large boxes given the capital requirements. So what, pacBio can't buy a MinION, an Ebola researcher in Guinea can !<br /><br />This "its not commercial" meme, given the numbers out there, is pure downplay. Seeking to belittle the threat and maintain a chauvinistic position.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-43321466428705322862016-11-04T01:41:26.054-04:002016-11-04T01:41:26.054-04:00As to ONT claiming that they are commercial, not ...As to ONT claiming that they are commercial, not sure how anyone can objectively believe that. Until you can order one without restrictions they will remain in only what can be described as an early access program. Just because they conveniently drop the "early" part of the name does not make it commercial. ONT can go and order a Sequel. ONT will be commercial when PacBio can order a Minion. <br /><br />As to PacBio lacking improvements - they went from 100k ZMWs to 1M on the Sequel. Their read lengths and output per flowcell have been going up steadily. And they have a hard working ethos to them, not some jerk CTO that makes comments unbecoming a corporate officer, e.g. accusing scientific competitors of plagiarism without a shed of evidence. <br /><br />One thing that must be noted is that because of the undisputed breakneck rate of improvement in their performance, both PacBio and ONT are rapidly coming up against physical limits of what the measurement technology is capable of. The next wave of improvements will have to come from the biochemistry. And everyone knows (or should know) that any hope for exponential improvements in chemistry is a pipe dream. Our phones would not be stuck at 12 hrs of battery life under moderate usage if that was not the case. Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-63056625777604835292016-11-03T19:07:05.930-04:002016-11-03T19:07:05.930-04:00In response to Dicky
1) Pacbio hasn't been o...In response to Dicky<br /><br />1) Pacbio hasn't been on the market for 8 years. They've been on the market only 5 years. But both ONT and Pacbio were founded in 2015. <br /><br />2) Pacbio went from 1k mean RL and 75k ZMW's to 20k mean RL and 150k ZMW's in 4 years. That's a 40x improvement in throughput. ONT has also been rapidly improving their chem. But a lot of the large throughput numbers are just very long run times >24h. You could take an RS chip and probably do some type of rinse and reuse to also get super long runs with high throughput. <br /><br />3) ONT is still a bit off from being commercially ready. Hand picking a few data points is easy, but having a product that works reliably for thousands of customers will be a big challenge. It took Sequel 1 year to really start performing how it should. It will take ONT a while to adjust from a development product to a commercial product. <br /><br />I don't think this lawsuit by Pacbio was done is desperation. It's very likely ONT is infringing on a patent. And it would be stupid for them not to go after it. Don't forget this is corperate America, where companies like Apple will sue over swiping. <br /><br />Also being forced to only use 1D reads will be a decent blow to ONT. Even if a 1D ready is in the 90-95% accuracy it still will be lower than the 99%+ by a 2D read. Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-92076813018358064642016-11-03T17:59:07.996-04:002016-11-03T17:59:07.996-04:00Hi Keith, really appreciate that. Thanks for writi...Hi Keith, really appreciate that. Thanks for writing back, I shall wait for your answer.Mohan Chennupatinoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-28885231184619979582016-11-03T17:49:26.545-04:002016-11-03T17:49:26.545-04:00Mohan: For the record I really think you ask some ...Mohan: For the record I really think you ask some good questions - please be a little patient with me for a full follow-up & ignorethe silliness above. Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-63323193615651037962016-11-03T16:58:56.981-04:002016-11-03T16:58:56.981-04:00Hi,
Just to be clear, I have no affiliations wit...Hi, <br /><br />Just to be clear, I have no affiliations with any of the companies, pacbio, oxford nanopore or Illumina. <br /><br />I was, as you can see from my comment above, biased towards Pacbio based on what I read, their papers in the big journals etc, and wanted to find out more considering their stock is now much cheaper to invest in. But it appears the comment section of this blog is not the place to find them.<br /><br />Thanks anyway.Mohan Chennupatinoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-17217692607063096892016-11-03T13:18:04.228-04:002016-11-03T13:18:04.228-04:00Hi,
No I think you're wrong i think its Mohan...Hi,<br /><br />No I think you're wrong i think its Mohan from UniCredit, an investment bank in London. Are UniCredit a big PacBio investor ? if so, then they are down 20% today and possibly a lot more to lose - what a waste of money. Perhaps that explains the "put all your money" comment ? I dunno.<br /><br />Felicity [not PacBio]Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-5721113540950906742016-11-03T12:45:55.907-04:002016-11-03T12:45:55.907-04:00I think the question is more about the affiliation...I think the question is more about the affiliation of the commenter with the legal aggressor, and the apparent bias in the comments, than a race thing surely ?; and how many Mohans can be working for the handful of DNA sequencing companies? If the commenter had signed off Felicity, and theres one Felicity on LinkedIN working for PacBio, would it be unreasonable to ask if its the same Felicity ? or would it be sexist ? Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-52667348321078991932016-11-03T12:08:54.311-04:002016-11-03T12:08:54.311-04:00Probably not a comment from the same person, more ...Probably not a comment from the same person, more like racist innuendo, considering that Mohan is an extremely common South Asian name...Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-11491770926520313712016-11-03T09:55:37.737-04:002016-11-03T09:55:37.737-04:00Is this comment from Mohan Holenarasipura, appare...Is this comment from Mohan Holenarasipura, apparently a PacBio employee ?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-57348889635065926762016-11-03T09:53:03.166-04:002016-11-03T09:53:03.166-04:00Adding to what Mohan has said,
Actually, PacBio h...Adding to what Mohan has said,<br /><br />Actually, PacBio have been on the market for maybe 8 years now and their accuracy and throughput have not improved much at all as if they have hit some sort of limit imposed by the measurement method. ONTs rate of improvement seems much faster in just 2 years, and i saw some videos online where they say the homopolymers can be dealt with in consensus initially and then in single molecule. I understand there are public domain tools that already do the consensus corrections ?<br /><br />Watching ONTs presentation the 1 D seems more reliable and easier if i understand it with, as keith says, an error rate better than PacBio.<br /><br />You can't claim PacBio have 'early indications' of a good technology, its over 8 years old, with ONT being 2 years. As I recall for the first 18 months or so of RSII outage there was very little if any data and no 3rd party publications at all.<br /><br />I think ONT only restrict direct competitors from MinION purchase, they say its not a pilot but is fully commercial with 2-3000 out there.<br /><br />As for their human genome, I think they said they'd done a preliminary analysis and would make it, or an updated version of it, available once they'd been thru it. It must take a fair bit of effort to scrutinise your first Human Genome, no doubt detractors would be looking to jump on, and exploit, any flaws or oversights - am i right ?<br /><br />Interesting comments Mohan, but they don't tally with what I've been able to find in the public domain.<br /><br />DickyAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-18153344375732054112016-11-03T08:21:43.021-04:002016-11-03T08:21:43.021-04:00Hi Keith, thanks for the interesting post.
You h...Hi Keith, thanks for the interesting post. <br /><br />You have a very good summary of the threats to Pacbio. <br /><br />Personally, I wouldn't really consider 10x or IGenomX as much as a threat if for instance, Pacbio reduces their cost as they hope to by loading more ZMWs. And these technologies would perform better on Pacbio over Illumina data.<br /><br />Regarding nanopore technologies, you mention the usual systematic homopolymer error, has there been any public research suggesting that this can improve ? This is a problem that all nanopore based techs have and have not solved for a while. The only direction appears to be searching for new pores and that appears to have only swapped one systematic error for another unless i am mistaken.<br /><br />I am curious to know what makes you optimistic that they can reduce this error, that would be very interesting. It's a long time waiting, much (?) longer than PacBio took to catch up with its earlier promises esp considering the rewards up for grabs.<br /><br />Also in terms of just using 1D, isn't that going to make it in general less reliable over using 2D ? I guess CCS is definitely a special feature for PacBio, enabling the same base to be read etc so it's not surprising they are defending it.<br /><br />One thing that PacBio has in their favor is the number of papers that are being published using their technology. That's an early indication of a good technology.<br />In a field that relies on openness and transparency, I guess ONT's restrictions on who can get their pilot minions do not reflect as well.<br /><br />For instance, ONT announced on 20th October that they had sequenced the human genome on a minion, but no data was released and still hasn't been released to my knowledge... It appears to fit a pattern of a lack of transparency atleast for a novice observer like me.<br /><br />While one would expect nanopore tech to be eventually successful, one would be equally worried if they put all their money into Oxford Nanopore i think.<br /><br /><br /><br />Thanks !<br />Mohan<br /><br />Mohan Chennupatinoreply@blogger.com