MiSeq Made Easy?

The first computer I ever tried to program was built from a kit by my brother and father.  The DATAC-1000 was a single-board machine, with that single printed circuit board about the area of a large laptop (image on page 9). Sporting a grand 1K of RAM, it was a grand machine.  User input-output was entirely through a set of binary touchpads and LEDs, though a cassette tape interface enabled storing and reading programs.  If I helped any with it, I might have sorted the resistors since I had just learned the color code.  The machine sported the same processor as some other machines of the time, such as the KIM-1 and the PET and even something called an Apple.

With that interface, it wasn't easy to do much but with my brother's help I wrote simple programs to add, subtract and multiply numbers (I probably wrote a divide program too).  Arch soon had a calculator keyboard interface, though you had to boot it each session via a series of commands on the binary touchpads.  Before long, we also had a nice monochrome video interface.  With that I played with a spaceflight simulator he wrote and Conway's Game of Life and Wumpus and a few other games.  I can't claim anything useful beyond Life ever got done, though that is a wonderful place to lose oneself.  The hardware was also a bit tricky; if I remember correctly the power supply received a bit of attention including larger heat dissipating fins for than the kit provided.  The cassette interface was always troublesome, often requiring multiple attempts to retrieve a program.  Still, it worked.

A few years later my Dad got me the Sinclair ZX81 in kit form; for $50 more you could get it assembled, but that would hardly train the youngest offspring in electronics, would it?  This had all of four integrated circuits, which not only gave it again 1K of memory but also a simple video interface and a BASIC interpreter and an ASCII keyboard.  Clearly the technology had advanced to deliver much more functionality yet with fewer parts.  Still, like the DATAC you either played with it or on it; nothing externally useful could really be done on it.

A few years later, we obtained one of early clones of the IBM PC.  This machine had much more than 1K and soon had some useful programming languages (it came with BASIC and we soon had APL and Pascal as better choices).  There were also decent word processing programs and some early spreadsheets (Turbo Pascal came with the source for a simple one).  Finally, a computer that could do useful things!  The original IBM PC still had a cassette interface, but it soon disappeared as nobody used it other than a few hackers.  Disks!!  What a wonderful invention!  As IBM liked to advertise, this was a computer anybody could use.  Of course, it was soon followed by a computer anybody could use easily, the first Mac.

I'm reminded of all this by some of the announcements and developments in the benchtop sequencing world.  Illumina has announced today a trio of products for the MiSeq environment, and two in particular are aimed at making this a sequencer for the masses. 

The three products for MiSeq are improved Nextera kits, an custom kit system for amplicon resequencing and a new bioinformatic environment for analyzing sequence.

The Nextera kits will enable genomic library construction in under 90 minutes, which is touted as much faster than any competition, and will cost about $75 per library.  I love the Nextera kit, as it gives the illusion at least that even I could successfully make sequencing libraries.

The amplicon resequencing approach is interesting.  I spoke at CHI's recent Providence meeting and described my work at Infinity trying to develop custom amplicon resequencing assays on the PGM platform (though I must emphasize, that is a choice driven by availability; as much as possible we strove to not marry a platform).  While we had much success, we also encountered difficulties with barcode representation and specific amplicons not working well.  What Illumina is offering is a bioinformatics environment (an extension of their existing DesignStudio for hybridization enrichment) to specify the targets of your amplicons.  Illumina then generates a whole custom kit for you, with pricing based on the number of samples you wish to target and the number of amplicons required to target your regions of interest. Design Studio also generates the necessary electronic manifest to set up your MiSeq for the run.  So Illumina takes on the risk of getting the designs right, rather than the investigator.  The protocol for actually generating sequencer-read amplicons is specified at 8 hours, meaning an industrious biologist can start first thing in the morning and load the sequencer before leaving.

The third bit is a bioinformatics analysis solution called Base Space, which lives in the cloud.  Teaser accounts will be made free for a number of months, after which the charge will be by the MiSeq run and estimated to be $20.  This may even be rolled into the consumables pricing.  Base Space will support a number of workflows currently on the instrument and is designed to support further workflows in the future.  These may include open source or commercial products.  Base Space also solves a minor issue with the MiSeq, which is it can either run sequencing or analyze a run, but not both simultaneously.  Data will be uploaded to BaseSpace roughly as it is generated.

So all of these are designed to make MiSeq accessible to the scientific masses.  You don't need to be a bioinformatic hacker to design or execute an amplicon sequencing experiment, and you won't need to be a master pipettor to set up genomic sequencing.   Sequencing for the masses; can ads with Charlie Chaplin be far behind?