Large-scale compression of genomic sequence databases with the Burrows-Wheeler transform

Motivation The Burrows-Wheeler transform (BWT) is the foundation of many algorithms for compression and indexing of text data, but the cost of computing the BWT of very large string collections has prevented these techniques from being widely applied to the large sets of sequences often encountered as the outcome of DNA sequencing experiments. In previous work, we presented a novel algorithm that allows the BWT of human genome scale data to be computed on very moderate hardware, thus enabling us to investigate the BWT as a tool for the compression of such datasets. Results We first used simulated reads to explore the relationship between the level of compression and the error rate, the length of the reads and the level of sampling of the underlying genome and compare choices of second-stage compression algorithm. We demonstrate that compression may be greatly improved by a particular reordering of the sequences in the collection and give a novel `implicit sorting' strategy that enables these benefits to be realised without the overhead of sorting the reads. With these techniques, a 45x coverage of real human genome sequence data compresses losslessly to under 0.5 bits per base, allowing the 135.3Gbp of sequence to fit into only 8.2Gbytes of space (trimming a small proportion of low-quality bases from the reads improves the compression still further). This is more than 4 times smaller than the size achieved by a standard BWT-based compressor (bzip2) on the untrimmed reads, but an important further advantage of our approach is that it facilitates the building of compressed full text indexes such as the FM-index on large-scale DNA sequence collections.Comment: Version here is as submitted to Bioinformatics and is same as the previously archived version. This submission registers the fact that the advanced access version is now available at http://bioinformatics.oxfordjournals.org/content/early/2012/05/02/bioinformatics.bts173.abstract . Bioinformatics should be considered as the original place of publication of this article, please cite accordingl

GPU-Accelerated BWT Construction for Large Collection of Short Reads

Advances in DNA sequencing technology have stimulated the development of algorithms and tools for processing very large collections of short strings (reads). Short-read alignment and assembly are among the most well-studied problems. Many state-of-the-art aligners, at their core, have used the Burrows-Wheeler transform (BWT) as a main-memory index of a reference genome (typical example, NCBI human genome). Recently, BWT has also found its use in string-graph assembly, for indexing the reads (i.e., raw data from DNA sequencers). In a typical data set, the volume of reads is tens of times of the sequenced genome and can be up to 100 Gigabases. Note that a reference genome is relatively stable and computing the index is not a frequent task. For reads, the index has to computed from scratch for each given input. The ability of efficient BWT construction becomes a much bigger concern than before. In this paper, we present a practical method called CX1 for constructing the BWT of very large string collections. CX1 is the first tool that can take advantage of the parallelism given by a graphics processing unit (GPU, a relative cheap device providing a thousand or more primitive cores), as well as simultaneously the parallelism from a multi-core CPU and more interestingly, from a cluster of GPU-enabled nodes. Using CX1, the BWT of a short-read collection of up to 100 Gigabases can be constructed in less than 2 hours using a machine equipped with a quad-core CPU and a GPU, or in about 43 minutes using a cluster with 4 such machines (the speedup is almost linear after excluding the first 16 minutes for loading the reads from the hard disk). The previously fastest tool BRC is measured to take 12 hours to process 100 Gigabases on one machine; it is non-trivial how BRC can be parallelized to take advantage a cluster of machines, let alone GPUs.Comment: 11 page

A representation of a compressed de Bruijn graph for pan-genome analysis that enables search

Recently, Marcus et al. (Bioinformatics 2014) proposed to use a compressed de Bruijn graph to describe the relationship between the genomes of many individuals/strains of the same or closely related species. They devised an $O(n \log g)$ time algorithm called splitMEM that constructs this graph directly (i.e., without using the uncompressed de Bruijn graph) based on a suffix tree, where $n$ is the total length of the genomes and $g$ is the length of the longest genome. In this paper, we present a construction algorithm that outperforms their algorithm in theory and in practice. Moreover, we propose a new space-efficient representation of the compressed de Bruijn graph that adds the possibility to search for a pattern (e.g. an allele - a variant form of a gene) within the pan-genome.Comment: Submitted to Algorithmica special issue of CPM201