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  • #46
    Betamax vs VHS???

    Any updates on the contest, is Ion keeping up with the PII promise? I keep hearing about people buying MiSeqs/HiSeqs here in Sweden but I have yet to see a IonProton? It feels as if Ion needs the PII to finally be competitive (HiSeq 1500 beats the PI, and MiSeq beats the PGM, Ion still needs more handson, much bigger footprint, no real answer to Nextera, no practical PE does this work as easy as in the MiSeq?).

    Is Ion going to be to little too late? It could be a problem if Illumina grabs the whole market before Ion gets a chance to develop the PII and PIII distribution lines/customer base. Once you have bought a MiSeq or a HiSeq it becomes very difficult to through it away and by a Proton even if it has 10x more coverage. If Illumina manages to sell, 100k-1M MiSeqs they might have a mass-production leverage that will be difficult to compete even if the Ion has a better product. Its not only about having the best product, its about having a good distribution, support, customer base, marketing and sales.

    Also I have trouble understanding Ion, why are they trying to compete with Illumina's HiSeq, that monster is soon to be obsolete "mainframe". You should be building $10k self contained push-go sequencers for hospitals/farmacies/small labs??? I see Core sequencing labs are bound to disappear in the next 5 years... Illumina is already making more money out of MiSeqs than with HiSeqs, take the hint.

    We need Ion to keep up the pressure in Illumina, otherwise she will turn into another lazy monopoly like Intel, unlikely to make any real advances because they have no real competition. My advice to Ion: you will never match Illumina at this pace, sell the PGM at cost, and make money on the consumables (printers/ink).... Or what about leasing the instruments? Ion you need to get out there FAST before Illumina get their hands in the whole market!!

    Note: Yes I bought a single MiSeq when I really wanted to buy an Ion (I'm a disgrunted wanna be Ion customer). We would have bought the Ion if it was cheaper than the MiSeq, but it had no Nextera, we had to buy the Covaris and the OneTouch, much higher hands-on prep time and a huge footprint. Today if they offer a Proton at the same price as a MiSeq we would have to say no because we already have a MiSeq, we already made the investment... This is our own particular experience, but I know we probably not a rare case. I hope that Ion's manager has a plan, down here in the ground their future seems quite dim.

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    • #47
      P.S: In retrospect, the MiSeq was the best choice, and still is the best choice for us. Had we bought the PGM we would be in a world of hurt as we have heard how people struggle with sample prep. Our MiSeq has delivered flawlessly, their phone/sales and onsight tech support immediate and impeccable (I worked for tech support for 4 years, these guys are amazing). My only complain is that they refused to release the sequence of their primers for Nextera, but that was an issue with their legal dep, tech support was very frank and direct about this. The guys on the phone basically told me: "you know this is very frustrating, we understand you perfectly and it makes no sense, but we have orders from our legal department not to respond this question".
      Last edited by aleferna; 02-14-2013, 02:06 AM.

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      • #48
        * The proton II chip should be shipping next month.
        * An answer to Nextera already exists: http://products.invitrogen.com/ivgn/product/4480829
        * Slow pace? You consider 10x improvement every 6 months to be slow?
        * Problems with slow/time consuming sample prep are being addressed with Avalance and IonChef

        In the end of the day the better sequencer will win. Still believe that its going to be the proton and am therefore not selling my shares any time soon (unless I will be forced to through a possible buyout).

        Things to look out for during the next month are going to be the AGBT meeting and whether the new chip ships as planed.

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        • #49
          Originally posted by steinmann View Post
          They have little to gain in lying to us.
          EVERY supplier has an incentive to lie. Not as "material lie" a la certain UK based company of yesteryear, but certainly exaggeration and puffing up. So far LT has shown a steady improvement, but far less and with at least 6 month lag over what they had promised. So yes, they are lying.

          3.: With the PGM they have shown that their technology works, that its scalable, generates sales and their announcements come true. Why believe that this should be any different for the Proton?
          Whoa, slow it down cowboy... What does "scalable" mean? Scalable as six months away? Or scalable as "has a decade of headroom". The latter is far from clear. ISFETs are inherently susceptible to noise in the subthreshold regime, and may not be operatable in a biological environment with modulated input. Signal only gets worse as well density increases, and cross-talk goes up too. Protons diffuse like there is no tomorrow. There are probably circuit and biochemical solutions to these problems, but that is pure speculation.

          Originally posted by steinmann View Post
          Slow pace? You consider 10x improvement every 6 months to be slow?
          10x is easy when you start out at rock bottom. 10x in another six months? Perhaps not.

          In the end of the day the better sequencer will win.
          Yeah, that is why the Betamax won. Most of the time cheap and robust wins over sexy. IT has a potential to be cheaper (natural dNTPs) and the jury is still out on robust. A likely outcome is that if both make steady progress they reach an equilibrium at some point and then pound the heck out of each other, to the benefit of the end user.
          Last edited by BBoy; 02-15-2013, 12:57 AM.

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          • #50
            Originally posted by BBoy View Post
            Yeah, that is why the Betamax won. Most of the time cheap and robust wins over sexy. IT has a potential to be cheaper (natural dNTPs) and the jury is still out on robust. A likely outcome is that if both make steady progress they reach an equilibrium at some point and then pound the heck out of each other, to the benefit of the end user.
            A more likely outcome is that one method is inherently superior and will kill the competitor.

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            • #51
              While Ion may have an inherent cost advantage, the homopolymer calling issue just won't go away. New entrants (e.g. QIAGEN, GnuBio) are likely to liven the competition for some of the very valuable clinical markets, while other new entrants (nanopores) are likely to make life interesting for the current players in other areas.

              There are plenty of arenas in which convergence to a single technology just doesn't happen. Or, it may well be that in 5 years that both ILMN and Ion have the current market position of 454 -- measurable, but clearly eclipsed by newer platforms.

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              • #52
                About Qiagen, they make more money on hybrid capture than anyone in the research world can imagine. So ngs for them is a hobby.

                Life is for sale because the already mighty want to cash in. It's been made incredibly lean to a very low R&D expenditure and growth on reduction. This will culminate in a buy out. Only thing is, the buyer could care less about NGS and Life will once again split up in two pieces. Word is Roche for you know what and Thermo for the rest.

                If this doesn't happen, also a big chance of that, there will be a lot of slow damage because it will be tough to come back and build up the skeleton. At that point, the stock will start a good decline. If you want to hold, there is no chance in hell a company will be a 15% premium over current prices. So wake up early...

                Right now everyone holding their breath and icing their wounds and stalling the big results for product intros.

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                • #53
                  The question is: You go to the doctor for some condition and before prescribing a particular medicine he swabs your mouth and puts it into his Pfizer subsidiced desktop genome analyzer which reads your DNA and outputs the specialized Pfizer medication required for your DNA/Height/Weight and age (thereby leveraging out any Generic drugss company from competing with them).

                  Now what brand is the desktop sequencer that he used? Which company is going to sell 1 Million sequencers that is whats at stake, "research sequencing" is where the real money is.

                  Personalized medicine(specially to fend of Generics), insurance, food/water/air biohazard sequencing this where the technology can really start returning investment. For this to happen the process has to be miniturized, robust, fool proof. So far Illumina seems to have the upper hand in this no?

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                  • #54
                    We are nowhere near that. Just like when they told me we would be flying cars around in 2000. Is that you Dr Collins ? Companies will go though gazillion iterations before that and CEO's will keep cashing in on that sale's pitch.

                    Comment


                    • #55
                      No I'm not sure who Dr Collins is, I'm just a bioinformatics phd student (with delusions of business).

                      Well, there is no real reason why you should have flying cars (you can still make lots of money on the road). I think this change will come quickly, because of market reasons, not due to innovations. There are two effects that I think will push the market wise adoption of these machines.

                      First, I think Big Farma is in a lot of "trouble". Well, ok they are some of the biggest most stable companies, but as far as I understand, they can't get the money back from drug development in the 20 years they get before the Generics flood the market and their revenues are filling the pinch for the first time. I think generics are taking a big bite out of there market and they will do whatever necesary to push them out. I see personalized "Coke Machine" drug platforms as the only way Big Farma can leverage their size to fend off the invasion of Generics. Of course mine is a very limited view of the marked, but that is the only way I can explain a $66-a-share bid for a sequencing company, I mean how else would you get ROI on that massive investment? I know we are far away from a real break-through but I've seen these companies sell mildly effective therapies with good advertisement (aka "inception"). I think that they could be able to convince the public that by reading their genome they can provide a custom made pill, which could be mildly true at first but enough to push the technology through. Unfortunately, the speed of innovation in medicine is directly proportional to the amount of money that you put into it, Big Farma has deep pockets and a huge problem.

                      Secondly, the US has a very disfunctional medical/judicial system. All is needed is a lawsuit, some cancer patient to sue his doctor for not doing a genome sequencing that would have helped him choose one chemo over another and voula... instant market appears. How many clinical tests are performed regardless of their efficacy just because there is a lawsuit behind them, how many machine's were sold to make such tests?? There are already some papers saying that sequencing the Leukemia genome helps you determine if you should do one chemo or another, the last one I saw hinted that in some cases you might want to skip chemo all together. I don't think it will be long before "ambulance chasers" find a way to sue doctors for not performing what is now a "cheap" and widely available test.

                      If you wait for these changes to happen for the "good of the patient", you are correct this would take decades and a "gazyllion" iterations, but if there is money to be made by lawyers or CEO's... well, then a few million in lobby money and a few well funded champion-data studies or a simple lawsuit might speed up the progress.

                      I'm not saying these things are morally correct, but companies do not have morals, they pursue revenue and they will push the system and the technology to suit their needs by any means necessary. Just look at all the "creative statistics" they been publishing in Phase 3 trials for new meds, how many were published for existing medications. I mean think about it, the public has a vague ambiguos idea of "the human genome", think how easy would it be to convince a big chunk of the public that these new state of the art black box technology that they know about but don't understand will improve their lives. A Pharma CEO could not ask for a better opportunity. I mean how hard can it be to convince "climate change deniers", vitamin takers, vaccine deniers, anti-socialism (you know republicans) that the new <<BigFarma name>> iOmics works?

                      I know this is a cynical view, and I do not support selling high-tech genomic snake oil. I do think however, that once this platform is deployed even if it is done for the wrong reasons, it will quickly evolve from marketing scheme to a real life-changing advance. I mean the internet was created by the army for all the wrong reasons and look at all the positive changes it has brought. Revolutions not always happen for the right reasons, but may end up with good consequences ... the problem is that if you don't understand the context in which they occur and the forces behind them they might converge to the wrong solution (just ask any Iranian). Scientists sometimes focus on their work so much that they block out the commercial and political impact of their work. This is dangerous, we should be mindful of external forces if we are to steer the upcoming genomic revolution into something useful for humanity.
                      Last edited by aleferna; 02-18-2013, 01:25 AM.

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                      • #56
                        Originally posted by krobison View Post
                        While Ion may have an inherent cost advantage, the homopolymer calling issue just won't go away. New entrants (e.g. QIAGEN, GnuBio) are likely to liven the competition for some of the very valuable clinical markets, while other new entrants (nanopores) are likely to make life interesting for the current players in other areas.

                        There are plenty of arenas in which convergence to a single technology just doesn't happen. Or, it may well be that in 5 years that both ILMN and Ion have the current market position of 454 -- measurable, but clearly eclipsed by newer platforms.
                        Dont think the homopolymer issue is a showstopper. To me it looks like they have improved to a level that can be considered good enough.

                        As for the possible competitors you mentioned its hard to take them seriously. The only one amongst them that is at least doing something truly interesting (oxford nanopore) wont even show up at this years AGBT.

                        The convergence does not need to happen, but given how fundamentally different the technologies are thats the most likely scenario. I am not saying that one of them is going to take 100% market share or that there wont be niches for things like super long reads. I am talking about a "kill" in the sense that Intel "killed" AMD.

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                        • #57
                          Originally posted by steinmann View Post
                          I am talking about a "kill" in the sense that Intel "killed" AMD.
                          And in turn Intel is getting clobbered by ARM, not because ARM is better on the same metrics but the metrics people care most about shifted.

                          Originally posted by steinmann View Post
                          Don't think the homopolymer issue is a showstopper. To me it looks like they have improved to a level that can be considered good enough.
                          Homopolymer issue might not be showstopper, but it is a royal pain. I'd be very curious if anyone trusts Ion data for finding frameshifts where it really matters (such as cancer samples), particularly in the face of low sample homogeneity.

                          Does anyone know if Ion has invested any in trying to fix this at level other than individual read? I.e., using suffix trees, kmers or other that look at whole set of reads? Definitely not something to attempt without informing user, but perhaps useful.

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                          • #58
                            Originally posted by krobison View Post
                            And in turn Intel is getting clobbered by ARM, not because ARM is better on the same metrics but the metrics people care most about shifted.
                            Funny that you say that. Intel happens to be my second largest long position

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                            • #59
                              Hi Aleferna, I am sorry but that vision is about 2 decades old and it's not gaining any traction. Just like ngs is not gaining ground in forensics and applied science.

                              Also, hope everyone sold their shares, life is officially way too expensive and that baby is slowly going to deflate.

                              Comment


                              • #60
                                Originally posted by aleferna View Post
                                Any updates on the contest, is Ion keeping up with the PII promise?
                                Not completely, they seem to be about six months off if you believe the latest statements from Rothberg at AGBT


                                Once you have bought a MiSeq or a HiSeq it becomes very difficult to through it away and by a Proton even if it has 10x more coverage.
                                That is only true in the RUO market, which is largely made up of NIH-funded purchases. In that market $100k is a lot of money. For a true commercial enterprise that is largely insignificant sum in the grand scheme of things. Ion Torrent likes to point to the semiconductor industry, and it is indeed useful to look there for what economies of scale look like. The big boys in that market depreciate sums in excess of $10B every few years. The major cost of switching platforms is not direct capital cost, but all the ancillary pain of re-establishing the surrounding infrastructure and the opportunity cost of establishing working relationships with a new supplier.

                                Also I have trouble understanding Ion, why are they trying to compete with Illumina's HiSeq, that monster is soon to be obsolete "mainframe". You should be building $10k self contained push-go sequencers for hospitals/farmacies/small labs???
                                Yeah, mainframes are nowhere to be seen anymore. Your phone runs on its own processing power. If there was ever a realization of Larry Ellison's "dumb terminal" vision, it is the "smart"phone. :-)

                                We need Ion to keep up the pressure in Illumina, otherwise she will turn into another lazy monopoly like Intel, unlikely to make any real advances because they have no real competition.
                                Your view of Intel is rather myopic. EVERY significant innovation in semiconductor process technology in the past decade has come from Intel, and everyone is copying them. The design side of the business is a somewhat different story with a complicated history, but "lazy" is not a word anyone who knows anything about Intel would use in describing the company.

                                My advice to Ion: you will never match Illumina at this pace, sell the PGM at cost, and make money on the consumables (printers/ink)....
                                Yeah, that worked out for HP real well...

                                Note: Yes I bought a single MiSeq when I really wanted to buy an Ion (I'm a disgrunted wanna be Ion customer). We would have bought the Ion if it was cheaper than the MiSeq, but it had no Nextera, we had to buy the Covaris and the OneTouch, much higher hands-on prep time and a huge footprint. Today if they offer a Proton at the same price as a MiSeq we would have to say no because we already have a MiSeq, we already made the investment... This is our own particular experience, but I know we probably not a rare case. I hope that Ion's manager has a plan, down here in the ground their future seems quite dim.
                                See, the ecosystem is usually far more important than any one particular component of it. The history of dominant enterprises shows that you cannot beat them at their own game, you have to shift the game. Today, at a very gross level the output of a P2 is very similar to that of a HiSeq: 200-ish bp scattershot reads, with perhaps lower consumable costs, but with a higher labor cost, perhaps a homopolymer issue that may or may not be important to many, and downside in the ecosystem (sample prep, informatics). If all IT can do is sacle output by making their chips bigger they are playing Illumina's game. (the cost of a YIELDING chip increases exponentially with area). If, on the other hand, they can make a 1B well chip and not have to rely on a HUMONGOUS 30mmx30mm die to do it then they are shifting the game and have a chance of eating the cake.

                                Speaking of that, does anyone have a sense how far IT can push well pitch? The latest PR statements from Rothberg imply around 1um pitch for the P2.

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