Superfast Sequencing: Prototype machines at Pacific Biosciences are being tested with bacterial DNA.
Credit: Justin Fantl

Features

Interpreting the Genome

  • January/February 2009
  • By Emily Singer

New technologies will soon make it possible to sequence thousands of human genomes. Now comes the hard part: understanding all the data.

   

The 12 prototypes look like prefabricated children's forts--boxes the size of freezers, faced with bright red plastic and grouped in twos and threes on a concrete floor at Pacific Biosciences, a startup in Menlo Park, CA. But the simple exterior of the machines belies the complexity within. Each box houses a small chip packed with thousands of strands of DNA from bacteria or viruses, each strand in a nano-sized well. An enzyme stuck to the bottom of each well speedily builds a corresponding strand, stringing together the bases, or chemical subunits of DNA, that pair properly with those of the original. Each of the four types of bases, represented by the letters A, T, C, and G, is labeled with a different fluorescent marker, which is activated by the reaction that attaches a new base to the strand. Because the machine tracks the reactions as they happen, it can churn out reams of raw data on the sequences of the DNA samples as fast as a built-in camera can record them.

A computer monitor installed next to each machine displays a snapshot of the action taking place. A series of lights scatter across the screen, bursting and fading in quick succession. Each flash lasts just tens of milliseconds, but its color indicates which of the four bases has just been added to a strand of DNA, and its position indicates where. The video must be slowed for viewing: the flashes come too fast for the human eye to process. Computer algorithms convert the pattern of flashes into DNA sequences hundreds to thousands of bases long. Additional algorithms then compare millions of these stretches of DNA, identify sequences that overlap at their ends, and fit the pieces together to capture a complete genome.

 

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