Integration of SAM sequencing with SBS sequencing

We propose that these SAM techniques could be advantageously integrated with highly parallel SBS array sequencing, as it can readily generate the sequence data for SAM algorithms to reassemble large contiguous regions, even from genomic clones containing repeated motifs, homopolymer regions or recalcitrant elements. The purpose of this paper is to demonstrate the advantages of SAM sequencing methods to alleviate the limitations of SBS technology and provide a basis for improved assembly of short-read data into long contiguous sequence. We have simulated SAM sequencing reactions as would be obtained from an SBS array platform, in which reads of length 100 or 150 bp were obtained from several independently mutated copies of fragments of genomic DNA up to 600 kb long, drawn from human and other genomes. We calculated the proportion of error from our reconstructions of original (wild-type) sequence. Our analyses indicate that SAM approaches would enable the de novo sequencing of megabase DNA fragments from short-read sequencing procedures, including regions of repetitive sequence and base-biased sequence.

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