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  • pmiguel
    Senior Member
    • Aug 2008
    • 2328

    Illumina to give better cost per base?

    Have you seen the investor press release:

    HiSeq 2500 chemistry enhancements empower the industry’s highest daily throughput and drive down the price of whole-genome sequencing. With support of paired 250 base pair read lengths in rapid run mode, the HiSeq 2500 will be capable of generating up to 300 Gb in rapid mode with sample to data in less than three days. These enhancements will be available in the second half of
    this year.
    Anyone tried to parse this to get the actual cluster density change?

    This would be 300 Gb from 4 lanes, right? (2 flow cells, 2 lanes per rapid flowcell).

    So 75 Gb per lane. That does sound like a lot. But much of that would come from the 100 --> 250 base read length shift.

    So 30 Gb per lane with 100 base reads. That does not sound so great. Using "high output" chemistry one gets 40-50 Gb per lane with 2x100 PE at optimum clustering densities. Although, I guess that is beyond spec for a HiSeq. But it is what you get.

    But, currently anyway, only 2 swaths per lane are scanned with Rapid chemistry, instead of the 3 swaths per lane scanned with High Output chemistry.

    So what does this mean for the actual increase in cluster density? 30 Gb at 2x100 base reads converts to 150 million clusters/lane. What is that? ~160K PF Clusters/mm^2 for 3 swaths, so 240Kclusters/mm^2 PF for a 2 swath lane?

    That is not bad, especially if quality is good out to 250 bases. However, I don't think it represents a dramatic price per base decrease. Of course that may not be the appropriate metric. 2x250 for de novo applications give you more than 2.5x the sequencing power of 2x100.

    I am bringing this up, because we have seen the hyper-Moore's rate increase in bases/$ for several years now. One always wonders when this will top out. My impression, which is purely the speculation of someone with zero inside connections in the industry, someone literally working in a hole in the ground (well, the sub-basement), is that Illumina is deliberately throttling back on the bases/$ acceleration to just what is needed to compete with the Proton Torrent.

    For instance, the 2 swaths/lane scanning of Rapid flow cells seems completely artificial to me. The lanes are clearly large enough to accept an additional swath. But this would have the effect of reducing the cost/base to below that of the "high output" chemistry.

    Personally, I am completely ready to kick the "high output" chemistry to the curb. I mean, it delivers, but 10 day runs are exhausting. And even minor problems in a run generally result in a week of troubleshooting, minimum, to get a fix. That kind of device period just isn't good for humans. At least if you have a single instrument. If you have several, you can just stagger the runs to get data coming off in even intervals.

    --
    Phillip
  • GenoMax
    Senior Member
    • Feb 2008
    • 7142

    #2
    Originally posted by pmiguel View Post
    I am bringing this up, because we have seen the hyper-Moore's rate increase in bases/$ for several years now. One always wonders when this will top out. My impression, which is purely the speculation of someone with zero inside connections in the industry, someone literally working in a hole in the ground (well, the sub-basement), is that Illumina is deliberately throttling back on the bases/$ acceleration to just what is needed to compete with the Proton Torrent.
    This is par for course like other technology companies. Intel regularly does it taking into consideration what AMD has on the horizon.

    Originally posted by pmiguel View Post
    For instance, the 2 swaths/lane scanning of Rapid flow cells seems completely artificial to me. The lanes are clearly large enough to accept an additional swath. But this would have the effect of reducing the cost/base to below that of the "high output" chemistry.
    --
    Phillip
    That may be true but it allows them to hedge their bets against the "next" great chemistry/technology not working out in time. By flicking an additional switch they can make an "improved" version available in short order (most likely at cost of additional run time though).

    I hate to use the microprocessor industry analogy again but there was a time when Intel was going to charge $$ to unlock additional cores on a processor that you could buy for cheap (with only half the cores working initially). I think that initiative died though.

    Comment

    • steinmann
      Member
      • Feb 2010
      • 64

      #3
      Originally posted by pmiguel View Post
      I am bringing this up, because we have seen the hyper-Moore's rate increase in bases/$ for several years now. One always wonders when this will top out. My impression, which is purely the speculation of someone with zero inside connections in the industry, someone literally working in a hole in the ground (well, the sub-basement), is that Illumina is deliberately throttling back on the bases/$ acceleration to just what is needed to compete with the Proton Torrent.
      In that case one should have expected a little more form Illumina. If things continue to go according to schedule for Ion Torrent the PII chip will be shipping next month.

      Comment

      • pmiguel
        Senior Member
        • Aug 2008
        • 2328

        #4
        Originally posted by GenoMax View Post
        This is par for course like other technology companies. Intel regularly does it taking into consideration what AMD has on the horizon.



        That may be true but it allows them to hedge their bets against the "next" great chemistry/technology not working out in time. By flicking an additional switch they can make an "improved" version available in short order (most likely at cost of additional run time though).

        I hate to use the microprocessor industry analogy again but there was a time when Intel was going to charge $$ to unlock additional cores on a processor that you could buy for cheap (with only half the cores working initially). I think that initiative died though.
        Yeah, this was exactly the analogy that occurred to me as well.

        --
        Phillip

        Comment

        • pmiguel
          Senior Member
          • Aug 2008
          • 2328

          #5
          Originally posted by steinmann View Post
          In that case one should have expected a little more form Illumina. If things continue to go according to schedule for Ion Torrent the PII chip will be shipping next month.
          Well, let's hope it is awesome. Then Illumina might "unlock" the Rapid flow cells to provide 50% more data.

          --
          Phillip

          Comment

          • steinmann
            Member
            • Feb 2010
            • 64

            #6
            Originally posted by pmiguel View Post
            Well, let's hope it is awesome. Then Illumina might "unlock" the Rapid flow cells to provide 50% more data.
            Or start looking like Kodak in 2001

            Comment

            • TonyBrooks
              Senior Member
              • Jun 2009
              • 303

              #7
              I believe there is a semi-ordered flowcell on the horizon that can deal with "significantly higher" cluster density.
              Here's hoping, it's Illumina making good on this patent http://www.google.com/patents/US20090226975

              No more over-clustering. Woo-hoo!!!

              Comment

              • HESmith
                Senior Member
                • Oct 2009
                • 512

                #8
                And I thought I was cynical ;-).

                Like Phillip, I have zero inside knowledge. However, since imaging is the most time-intensive step, I assume that two-swath scanning is the trade-off for keeping the run time relatively short (~one day for 2x150 fast mode).

                And Tony, thanks for the optimism re: semi-ordered flow cell. +1 Woo-hoo!

                Harold

                Comment

                • pmiguel
                  Senior Member
                  • Aug 2008
                  • 2328

                  #9
                  Originally posted by HESmith View Post
                  And I thought I was cynical ;-).

                  Like Phillip, I have zero inside knowledge. However, since imaging is the most time-intensive step, I assume that two-swath scanning is the trade-off for keeping the run time relatively short (~one day for 2x150 fast mode).

                  And Tony, thanks for the optimism re: semi-ordered flow cell. +1 Woo-hoo!

                  Harold
                  Okay, but why not include the option to scan that 3rd swath per surface at a cost of some time? I think 2x150 Rapid mode takes 2 days -- at least with both flow cells loaded, right? Even if chemistry was never the limiting factor, then scanning one extra swath per surface should take an extra 50% of the time. 3 days.

                  Run the numbers, that would make "semi-rapid" runs cheaper per base than "high output" chemistry.

                  Call me cynical if you like, but remember Illumina's CEO blaming a down-turn in profits last year on the v1->v3 transition that nearly tripled the bases/$ generated with Illumina chemistry. Of course the economy was still tanking last year and that transition put the nails in the SOLiD's coffin, but apparently these were subtleties not likely to play well to investors.

                  --
                  Phillip

                  Comment

                  • snetmcom
                    Senior Member
                    • Oct 2008
                    • 159

                    #10
                    Originally posted by TonyBrooks View Post
                    I believe there is a semi-ordered flowcell on the horizon that can deal with "significantly higher" cluster density.
                    Here's hoping, it's Illumina making good on this patent http://www.google.com/patents/US20090226975

                    No more over-clustering. Woo-hoo!!!
                    Ordered flowcells have been shown for the last 4 years. Doesn't mean we will get them at a reasonable cost.

                    Comment

                    • GenoMax
                      Senior Member
                      • Feb 2008
                      • 7142

                      #11
                      Originally posted by snetmcom View Post
                      Doesn't mean we will get them at a reasonable cost.
                      There will be no way to determine if the pricing is "reasonable" (only a few people likely know what it actually costs to make the flowcells and they are not likely to disclose that info here).

                      Cost will ultimately be what the market will be willing to bare.

                      Comment

                      • ymc
                        Senior Member
                        • Mar 2010
                        • 496

                        #12
                        Similar thing happens in the CPU and GPU market. Even if their techies might want to bring the latest tech to the market, they will be stopped cold by the marketing people. From the point of view of making the most $$$, I think this makes sense.

                        That's why we need competitions. Let's hope PII is as good as it claims.

                        Comment

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