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Improving DNA Sequencing Accuracy and Throughput

  • David O. Nelson
Conference paper
Part of the The IMA Volumes in Mathematics and its Applications book series (IMA, volume 81)

Abstract

LLNL is beginning to explore statistical approaches to the problem of determining the DNA sequence underlying data obtained from fluorescence-based gel electrophoresis. Among the features of this problem that make it interesting to statisticians include:
  • • 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.

Keywords

Original Signal Fredholm Integral Equation Base Calling Lawrence Livermore National Laboratory Reverse Complement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • David O. Nelson
    • 1
    • 2
  1. 1.Lawrence Livermore National LaboratoryLivermoreUSA
  2. 2.Statistics DepartmentUniversity of CaliforniaBerkeleyUSA

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