Improving DNA Sequencing Accuracy and Throughput
• the underlying mechanics of electrophoresis is quite complex and still not completely understood;
• the yield of fragments of any given size can be quite small and variable;
• the mobility of fragments of a given size can depend on the terminating base;
• the data consists of samples from one or more continuous, non-stationary signals;
• boundaries between segments generated by distinct elements of the underlying sequence are ill-defined or nonexistent in the signal; and
• the sampling rate of the signal greatly exceeds the rate of evolution of the underlying discrete sequence.
Current approaches to base calling address only some of these issues, and usually in a heuristic, ad hoc way. In this article we describe some of our initial efforts towards increasing base calling accuracy and throughput by providing a rational, statistical foundation to the process of deducing sequence from signal.
KeywordsPorosity Migration Phosphorus Hydroxyl Electrophoresis
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