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BULLET: a computer simulation of shotgun DNA sequencing

G D Smith1, K E Bernstein

  • 1Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Computer Applications in the Biosciences : CABIOS
|April 1, 1995
PubMed
Summary

BULLET software simulates DNA shotgun sequencing. Doubling fragment size doubles reactions for 80% sequence, but 100% sequence has a non-linear relationship, allowing formula derivation for reaction estimation.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Shotgun sequencing is crucial for DNA fragment assembly.
  • Estimating sequencing reactions is vital for cost and efficiency.
  • Existing models may not accurately predict reactions for complete sequence coverage.

Purpose of the Study:

  • To evaluate the relationship between DNA fragment size and sequencing reactions needed.
  • To develop predictive formulas for DNA sequencing effort.
  • To identify an optimal point for strategy transition in DNA sequencing projects.

Main Methods:

  • Utilized the BULLET computer program for DNA shotgun sequencing simulation.
  • Simulated sequencing of DNA fragments ranging from 2 to 30 kb.
  • Derived linear formulae based on simulation data to estimate sequencing reactions.

Main Results:

  • A linear relationship exists between DNA fragment size and reactions for 80% sequence coverage.
  • Doubling fragment size requires doubling sequencing reactions for 80% coverage.
  • A non-linear relationship complicates prediction for 100% sequence coverage.

Conclusions:

  • Developed linear formulae to estimate sequencing reactions for partial DNA sequencing.
  • 80% double-stranded sequence determination yields approximately 98% single-stranded sequence.
  • Suggests transitioning to a directed sequencing strategy at 80% coverage is efficient.

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