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  • #31
    Originally posted by TonyBrooks View Post
    For research the $1000 genome is great. For clinical applications, you need to be looking at the $100 genome or maybe even the $10 genome if you have a public health service and are a trillion dollars in debt (like the UK is).

    My experiences working in research is that the cost of sequencing is fine at the moment when using our Illumina machines. I'm not sure how many researchers would want to routinely do whole genomes as the analysis would be a bit challenging.

    About 10-15% of the cost of any project we undertake comprise of sequencing. The remainder are split between staff and sample prep.
    Bottom line: We need cheaper scientists and cheaper library prep kits!
    Yes, a 100$ genome will be more awesome and have a larger clinical impact than a 1000$ genome.

    Yes, the prices are pretty amazing right now compared to a few years ago, but not quite at the level where its something that you would do as casually and fast as a qPCR. Thats what I am looking forward to.

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    • #32
      The irritating thing about this is that Roche could pour enough money into 454 development to make it competitive with Illumina. They apparently have not thought it worthwhile.

      Illumina has a lot going for it, but where they seem unique to me is their level of tech support. Tech support from nearly every company I have ever dealt with tends towards to be close to a "nearly worthless" line. I presume this is "by design". Tech support is no doubt expensive and good tech support probably more so. Douglas Adam's was not far from the truth with his parody of this issue, with his depiction of the Complaints Department of the Sirius Cybernetics Corporation and their motto "Go Stick Your Head in a Pig". Seems like resisting the urge to cut tech support requires a sort of fortitude that larger companies just can't come by.

      But I suppose there is also just a level of prestige that Illumina offers in the industry. They have plundered the workforces of their competitors, often luring away their best and brightest. But I suppose there is nothing like being bought by a diagnostics giant to turn a trend like that on its head. Could be worse. They could have been purchased by GE.

      --
      Phillip

      Comment


      • #33
        Originally posted by steinmann View Post
        You are not making any sense whatsoever. Both IonTorrent and 454 do sequencing by synthesis (SBS)! The major problems with 454 sequencing are the optics required for detection and limited throughput. The IonTorrent chips were explicitly designed to address these limitation.
        Alright, if you want to get technical then yes, pretty much all of the NGS on the market use SBS. HOWEVER, the Illumina does a single iterative base for each synthesis step incorporating all 4 nucleotides at the same time, while the 454 and ion torrent flow each nucleotide across separately, watching for incorporation at each step.

        And yes, the semiconductor methodology of the ion torrent does address the optical drawbacks of the 454 but it's still the same process overall. It's still going to have homopolymer problems. It's still going to rely on bead deposition on a plate or chip or whatever. It's still going to have the problem inherent with emPCR.

        Finally, perhaps we could move the ion vs illumina discussion to another thread and not derail the discussion of the general dread caused by Roche trying to snatch up Illumina?

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        • #34
          Originally posted by pmiguel View Post
          The irritating thing about this is that Roche could pour enough money into 454 development to make it competitive with Illumina. They apparently have not thought it worthwhile.
          Exactly. The development of both SOLiD and Ion Torrent - both emPCR instruments - shows that they could have scaled 454 way further than they did, and also made steps to automate the fiddly library preparation (e.g. OneTouch). But they apparently chose not to, or couldn't for some reason. (No I don't count the REM e-System).

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          • #35
            Originally posted by steinmann View Post
            You are not making any sense whatsoever. Both IonTorrent and 454 do sequencing by synthesis (SBS)! The major problems with 454 sequencing are the optics required for detection and limited throughput. The IonTorrent chips were explicitly designed to address these limitation.
            I agree the IonTorrent is just a 454 with a different sensor. It should have a slight advantage in the level of signal discrimination by using a pH meter versus a CCD - though not sure we've seen it. However while it's true Ion reads seem to be under Q valued, and Illuminas over, it looks like Ion reads ARE lower quality than Illuminas or 454 reads.

            While pyrosequencing is a form of SBS it is different to Illuminas as it doesn't use reversible terminators so it has the same issues with homopolymers in 454 or IonTorrent. If you think it doesn't have an issue with homopolymers then I'd like to see it sequence some polyA tails.

            Don't get hung up on semiconductors versus optics - it's all post light marketing. Flourogenic sequencing is more sensitive than either 454 or Ion method http://www.nature.com/nmeth/journal/...meth.1629.html. And both Helicos and PacBio show that you can sequencing single molecules with optics.

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            • #36
              Originally posted by pmiguel View Post
              The irritating thing about this is that Roche could pour enough money into 454 development to make it competitive with Illumina. They apparently have not thought it worthwhile.
              Where could they go with 454 that ion torrent is not already going?

              And everybody poaches from everybody in the industry, particularly Illumina from ABI/Life. My Illumina sales rep tried to sell me on a SOLiD years ago, and some of the field service reps/managers worked on 3700's in my former lab.

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              • #37
                Originally posted by nickloman View Post
                Exactly. The development of both SOLiD and Ion Torrent - both emPCR instruments - shows that they could have scaled 454 way further than they did, and also made steps to automate the fiddly library preparation (e.g. OneTouch). But they apparently chose not to, or couldn't for some reason. (No I don't count the REM e-System).
                Yeah, I can't recall how many people I pestered at Roche about something called Raindance, that was going to revolutionize emPCR...

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                • #38
                  Originally posted by GW_OK View Post
                  Where could they go with 454 that ion torrent is not already going?
                  Too late now, they should have done more back in 2009 (not just announce 1kb reads).

                  Comment


                  • #39
                    Originally posted by TonyBrooks View Post
                    For research the $1000 genome is great. For clinical applications, you need to be looking at the $100 genome or maybe even the $10 genome if you have a public health service and are a trillion dollars in debt (like the UK is).
                    That's what people said about the $100,000 a year drug. The cost of sequencing is not what is keeping sequencing out of the clinic at this point. And it's probably not even the cost of data analysis. It's mostly that we just don't have much of a reason to be sequencing people's genomes at this point.
                    --------------
                    Ethan

                    Comment


                    • #40
                      Originally posted by pmiguel View Post
                      The irritating thing about this is that Roche could pour enough money into 454 development to make it competitive with Illumina. They apparently have not thought it worthwhile.
                      I'm not sure I agree with this...Roche has probably realized what most people have...that emulsion and beads will never compete with clustering in the mythical "clinic".

                      Comment


                      • #41
                        Originally posted by ECO View Post
                        I'm not sure I agree with this...Roche has probably realized what most people have...that emulsion and beads will never compete with clustering in the mythical "clinic".
                        Yeah, maybe so. If they purchase Illumina, suddenly all that IP is theirs to exploit. Reversible terminators, Bridge PCR -- no problem.

                        Say Roche is successful, what do things look like 1 year from now?

                        --
                        Phillip

                        Comment


                        • #42
                          Originally posted by pmiguel View Post
                          Say Roche is successful, what do things look like 1 year from now?

                          Human sacrifice, dogs and cats living together, mass hysteria...

                          Seriously though, Roche promises PE1000 in the next quarter, but won't be released until several years later when 90% of the market has already switched to Oxford Nanopore...

                          Comment


                          • #43
                            I wish folks would stop about the 100$ genome, 100$ of garbage in is garbage out... I hate to be so blunt but please give me a direct clear clinical setting where a WGS system saves lives as opposed to clean water, running shoes and measuring one's girth over time... The cost of implimenting a new technology in a health system is tremendous and requires an enourmous social pull... The common patient has been told that sequencing would save his life for the last 15 years... Roche knows this and it's buying price is the expression of this, I woulnd't be suprise if Flatley knows also... If I hear another ridiculous marketing hype about the revolution of the cancer single bullet, I'm gonna faint. I'm sure a few folks made some nice sells today, cause it's all about your options, not your condition.

                            Comment


                            • #44
                              Originally posted by Elcannibal View Post
                              I wish folks would stop about the 100$ genome, 100$ of garbage in is garbage out... I hate to be so blunt but please give me a direct clear clinical setting where a WGS system saves lives as opposed to clean water, running shoes and measuring one's girth over time... The cost of implimenting a new technology in a health system is tremendous and requires an enourmous social pull... The common patient has been told that sequencing would save his life for the last 15 years... Roche knows this and it's buying price is the expression of this, I woulnd't be suprise if Flatley knows also... If I hear another ridiculous marketing hype about the revolution of the cancer single bullet, I'm gonna faint. I'm sure a few folks made some nice sells today, cause it's all about your options, not your condition.
                              As much as we might wish otherwise, large health systems are not always focused on saving lives. Reducing the cost of delivering the current level of care is another. Choosing the right chemotherapy drug can save costs both in terms of saving on expensive drugs and avoiding expensive side effects. Identifying cases of rare disorders is far more efficient than flailing away with bad diagnoses, and is more humane.

                              For various reasons good and bad, large health systems also have little if any ability to alter some of these things. Forcing healthy choices (even when it is agreed what they are!) is not trivial in a democracy; look at the spectacular lack of success with Prohibition. So health systems go for what they can.

                              Sequencing in the clinic is happening NOW! Large U.S. medical centers are making it routine for cancer care, and that will percolate into the rest of the system. Now, most of that is amplicon sequencing, but it is still sequencing on a broad scale.

                              Comment


                              • #45
                                Originally posted by matholomew View Post
                                Don't get hung up on semiconductors versus optics - it's all post light marketing. Flourogenic sequencing is more sensitive than either 454 or Ion method http://www.nature.com/nmeth/journal/...meth.1629.html. And both Helicos and PacBio show that you can sequencing single molecules with optics.
                                I am confused. Helicos and PacBio are the perfect examples to support my point. Why do you think that Helicos is dead and PacBio slowly dying? Yes, flurogenic sequencing of single molecules is pretty damn cool, but error rates are way too high and the machines are the most expensive and unreliable ones on the market.

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