Assembly algorithms for next-generation sequence data

Aakrosh Ratan · 2009

*Signatures are on file in the Graduate School. ii Next-generation sequencing is revolutionizing genomics, promising higher coverage at a lower cost per base when compared to Sanger sequencing. Shorter reads and higher error rates from these new instruments necessitate the development of new algorithms and software. This dissertation describes approaches to tackle some problems related to genome assembly with these short frag-ments. We describe YASRA (Yet Another Short Read Assembler), that performs comparative assem-bly of short reads using a reference genome, which can differ substantially from the genome being sequenced. We explain the algorithm and present the results of assembling one ancient-mitochondrial and one plastid dataset. Comparing the performance of YASRA with the AMOScmp-shortReads and Newbler mapping assemblers (version 2.0.00.17) as template genomes are var-ied, we find that YASRA generates fewer contigs with higher coverage and fewer errors. We also analyze situations where the use of comparative assembly outperforms de novo assembly, and

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