Efficient Coding Strategies for DNA Sequencing

Enzymatic dideoxy sequencing can be streamlined using algebraic coding strategies from communications theory. Using coding methods similar to those applied to telecommunications and digital electronics, the speed and efficiency of DNA sequencing can be substantially improved. One DNA template can be sequenced using three mixed dideoxy reactions and data channels; two templates can be read simultaneously in five channels. Having demonstrated that such 3-channel coding and 5:2 source code compression can be applied to 35-S dideoxy sequencing, experiments are proposed to improve the speed and efficiency of (i) multiplex DNA sequencing, (ii) PCR-based sequencing, (iii) automated multi-fluor sequencing, and (iv) automated multi-channel/single fluor sequencing. Proposed experiments are a cost-effective means of significantly improving a variety of existing manual and automated DNA sequencing techniques by 33-60%; further improvements are possible.