SOLiD Sequencing

Applied Biosystems has just launched their instrument, which supports their version of high-throughput sequencing chemistry, termed “SOLiD™” (little “i”, please). Acquired from Agencourt Personal Genomics in late 2006, SOLiD is a unique parallel chemistry which enables simultaneous sequencing of thousands of individual DNA molecules.

Here I will present a brief overview of the technology, aimed at those who haven’t had time to become intimately familiar with the chemistry. Figures and information taken directly from this presentation from ABI’s website.

Sequencing on the SOLiD machine starts with library preparation. In the simplest fragment library, two different adapters are ligated to sheared genomic DNA (left panel of Fig. 1). If more rigorous structural analysis is desired, a “mate-pair” library can be generated in a similar fashion, be incorporating a circularization/cleavage step prior to adapter ligation (right panel of Fig.1).

Figure 1. Library generation schematic.

Once the adapters are ligated to the library, emulsion PCR is conducted using the common primers to generate “bead clones” which each contain a single nucleic acid species.

Figure 2. Clonal bead library generation via emulsion PCR.

Each bead is then attached to the surface of a flow cell via 3’ modifications to the DNA strands.