DNA sequencing gets SOLiD with built-in error detection

December 28th, 2009

Applied Biosystems, now part of Invitrogen, was the first to pioneer a sequencing-by-ligation process, marketing it under the name of SOLiD. The process has some interesting features and is the only sequencing approach to include a degree of built in error-detection, which can drop its error rates below that of traditional sequencing. But it was first of its kind, far more complex than previous methods, and ABI’s own literature on it skipped past key technical details—as a result, it confused most people. When talking with several people involved in genome sequencing, none would let me finish the sentence “I don’t understand how SOLiD works…”—they’d all interrupt by saying “Nobody understands SOLiD sequencing.”

Fortunately, I have a friend at ABI, and I now understand it. It’s really quite clever.

The process starts with a step that’s shared by the other two major sequencing techniques, which we’ll term tethered PCR. Tethered PCR creates a small population of identical molecules to sequence, but keeps them in close physical proximity so that they can be sequenced as a group.