Estimation of the Redundancy in Human Genome Shotgun Sequencing by a Monte-Carlo Simulation

Ayumu SAITO and Koichi NISHIGAKI*

Department of Functional Materials Science, Saitama University,
255 Shimo-okubo, Urawa, Saitama 338-8570, Japan

(Received: November 16, 1998; Accepted for publication: November 30, 1998; Published on Web: January 14, 1999)

In order to quantitatively comprehend the essence of whole genome shotgun sequencing, a Monte-Carlo simulation was carried out. It was estimated that even a vast genome such as human genome can be sequenced at a moderate redundancy (~7) with a satisfactory accuracy (10-4 error rate), resulting in a high sequencing speed and much lower cost. Switching from a random process (i.e., shotgun) to a directed process such as PCR-relay was shown to be ultimately important for a whole genome shotgun sequencing not to inflate its cost. An equation to evaluate the optimum switching point was introduced as a function of coverage, which also depends on the costs of a shotgun process and a directed one for sequencing a unit length. Moderate redundancy was underscored to have more merits in speed and accuracy than its demerit of being redundant. Our simulation for estimating redundancy was basically consistent with the results of the current whole genome shotgun sequencing. As a conclusion, whole genome shotgun sequencing applied to a vast genome is estimated to be effective.

Keywords: Monte-Carlo simulation, Whole genome shotgun sequencing, Human genome, Redundancy, PCR-relay, Random process

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