Joint base-calling of two DNA sequences with factor graphs

To improve the utility of existing technologies based on Sanger sequencing, this paper examines the possibility of base-calling two superposed DNA sequences jointly. This approach allows a single electrophoresis experiment to process two sequences, using the same quantity of reagents and machine hours as for a single sequence. A practical heuristic is proposed to first estimate the peak parameters, then separate them into two sequences (major/minor) by passing messages on a factor graph. Base-calling on the major alone yields accuracy commensurate with single sequence approaches, and joint base-calling provides results for the minor which, while being of lesser quality, incurs no additional cost and can be ultimately used in the genome assembly process.