Parallel de novo assembly of large genomes from high-throughput short reads

摘要

The advent of high-throughput short read technology is revolutionizing life sciences by providing an inexpensive way to sequence genomes at high coverage. Exploiting this technology requires the development of a de novo short read assembler, which is an important open problem that is garnering significant research effort. Current methods are largely limited to microbial organisms, whose genomes are two to three orders of magnitude smaller than complex mammalian and plant genomes. In this paper, we present the design and development of a parallel de novo short read assembler that can scale to large genomes with high coverage. Our approach is based on the string graph formulation. Input reads are mapped to short paths, and the genome is reconstructed as a superpath anchored by distance constraints inferred from read pairs. Our method can handle a mixture of multiple read sizes and multiple paired read distances. We present parallel algorithms for string graph construction, string graph compaction, graph based error detection and removal, and computing aggregate summarization of paired read links across graph edges. Using this, we navigate the final graph structure to reproduce large contiguous sequences from the underlying genome. We present a validation of our framework on experimental and simulated data from multiple known genomes and present scaling results on IBM Blue Gene/L.