0000000001165821
AUTHOR
Anthony J. Cox
Lightweight BWT Construction for Very Large String Collections
A modern DNA sequencing machine can generate a billion or more sequence fragments in a matter of days. The many uses of the BWT in compression and indexing are well known, but the computational demands of creating the BWT of datasets this large have prevented its applications from being widely explored in this context. We address this obstacle by presenting two algorithms capable of computing the BWT of very large string collections. The algorithms are lightweight in that the first needs O(m log m) bits of memory to process m strings and the memory requirements of the second are constant with respect to m. We evaluate our algorithms on collections of up to 1 billion strings and compare thei…
Lightweight LCP construction for next-generation sequencing datasets
The advent of "next-generation" DNA sequencing (NGS) technologies has meant that collections of hundreds of millions of DNA sequences are now commonplace in bioinformatics. Knowing the longest common prefix array (LCP) of such a collection would facilitate the rapid computation of maximal exact matches, shortest unique substrings and shortest absent words. CPU-efficient algorithms for computing the LCP of a string have been described in the literature, but require the presence in RAM of large data structures. This prevents such methods from being feasible for NGS datasets. In this paper we propose the first lightweight method that simultaneously computes, via sequential scans, the LCP and B…
Lightweight LCP construction for very large collections of strings
The longest common prefix array is a very advantageous data structure that, combined with the suffix array and the Burrows-Wheeler transform, allows to efficiently compute some combinatorial properties of a string useful in several applications, especially in biological contexts. Nowadays, the input data for many problems are big collections of strings, for instance the data coming from "next-generation" DNA sequencing (NGS) technologies. In this paper we present the first lightweight algorithm (called extLCP) for the simultaneous computation of the longest common prefix array and the Burrows-Wheeler transform of a very large collection of strings having any length. The computation is reali…
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 leng…
Lightweight algorithms for constructing and inverting the BWT of string collections
Recent progress in the field of \{DNA\} sequencing motivates us to consider the problem of computing the Burrows‚ÄìWheeler transform (BWT) of a collection of strings. A human genome sequencing experiment might yield a billion or more sequences, each 100 characters in length. Such a dataset can now be generated in just a few days on a single sequencing machine. Many algorithms and data structures for compression and indexing of text have the \{BWT\} at their heart, and it would be of great interest to explore their applications to sequence collections such as these. However, computing the \{BWT\} for 100 billion characters or more of data remains a computational challenge. In this work we ad…
Comparing DNA sequence collections by direct comparison of compressed text indexes
Popular sequence alignment tools such as BWA convert a reference genome to an indexing data structure based on the Burrows-Wheeler Transform (BWT), from which matches to individual query sequences can be rapidly determined. However the utility of also indexing the query sequences themselves remains relatively unexplored. Here we show that an all-against-all comparison of two sequence collections can be computed from the BWT of each collection with the BWTs held entirely in external memory, i.e. on disk and not in RAM. As an application of this technique, we show that BWTs of transcriptomic and genomic reads can be compared to obtain reference-free predictions of splice junctions that have h…
Adaptive reference-free compression of sequence quality scores
Motivation: Rapid technological progress in DNA sequencing has stimulated interest in compressing the vast datasets that are now routinely produced. Relatively little attention has been paid to compressing the quality scores that are assigned to each sequence, even though these scores may be harder to compress than the sequences themselves. By aggregating a set of reads into a compressed index, we find that the majority of bases can be predicted from the sequence of bases that are adjacent to them and hence are likely to be less informative for variant calling or other applications. The quality scores for such bases are aggressively compressed, leaving a relatively small number at full reso…