Abstract
Multiple displacement amplification (MDA) is a fast non-PCR based isothermal DNA amplification method that can amplify small amounts of DNA samples to a reasonable quantity for genomic analysis. This technique is suitable for metagenomics and single cell genome sequencing and related analyses. The distribution of the coverage of the output amplicons for single cell MDA unlike the multiceli amplification is not uniform. This distribution is unknown, and the parameters that affect this amplification bias have not been studied thoroughly. To have a better understanding of the MDA reaction we have developed a simplified mathematical model and the corresponding simulation algorithm called MDAsim to obtain a generative model for the output amplicons. In this paper we will show that the output coverage of MDAsim matches the experimental coverage very well. Therefore, the combination of MDAsim and a sequencing simulator can be utilized for test and evaluation of single cell assemblers avoiding the burden of experimental sequencing. Our results suggest that modelling the MDA mechanism and simulation of such increasingly complex models may provide valuable insight into the MDA process, which in turn can be used to design more efficient MDA reactions.
Published Version
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