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. 2013 Oct 1;29(19):2395-401.
doi: 10.1093/bioinformatics/btt420. Epub 2013 Aug 5.

Distilled Single-Cell Genome Sequencing and De Novo Assembly for Sparse Microbial Communities

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Free PMC article

Distilled Single-Cell Genome Sequencing and De Novo Assembly for Sparse Microbial Communities

Zeinab Taghavi et al. Bioinformatics. .
Free PMC article

Abstract

Motivation: Identification of every single genome present in a microbial sample is an important and challenging task with crucial applications. It is challenging because there are typically millions of cells in a microbial sample, the vast majority of which elude cultivation. The most accurate method to date is exhaustive single-cell sequencing using multiple displacement amplification, which is simply intractable for a large number of cells. However, there is hope for breaking this barrier, as the number of different cell types with distinct genome sequences is usually much smaller than the number of cells.

Results: Here, we present a novel divide and conquer method to sequence and de novo assemble all distinct genomes present in a microbial sample with a sequencing cost and computational complexity proportional to the number of genome types, rather than the number of cells. The method is implemented in a tool called Squeezambler. We evaluated Squeezambler on simulated data. The proposed divide and conquer method successfully reduces the cost of sequencing in comparison with the naïve exhaustive approach.

Availability: Squeezambler and datasets are available at http://compbio.cs.wayne.edu/software/squeezambler/.

Figures

Fig. 1.
Fig. 1.
The divide and conquer algorithm for an example with 10 cells and 3 distinct genomes shown in different colors. Each row corresponds to one sequencing round. The number of barcodes in each round is the number of blue boxes in the corresponding row

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