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 realized by performing disk data accesses only via sequential scans, and the total disk space usage never needs more than twice the output size, excluding the disk space required for the input. Moreover, extLCP allows to compute also the suffix array of the strings of the collection, without any other further data structure is needed. Finally, we test our algorithm on real data and compare our results with another tool capable to work in external memory on large collections of strings.Comment: This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The final version of this manuscript is in press in Journal of Discrete Algorithm

Metagenomic analysis through the extended Burrows-Wheeler transform

Background: The development of Next Generation Sequencing (NGS) has had a major impact on the study of genetic sequences. Among problems that researchers in the field have to face, one of the most challenging is the taxonomic classification of metagenomic reads, i.e., identifying the microorganisms that are present in a sample collected directly from the environment. The analysis of environmental samples (metagenomes) are particularly important to figure out the microbial composition of different ecosystems and it is used in a wide variety of fields: for instance, metagenomic studies in agriculture can help understanding the interactions between plants and microbes, or in ecology, they can provide valuable insights into the functions of environmental communities. Results: In this paper, we describe a new lightweight alignment-free and assembly-free framework for metagenomic classification that compares each unknown sequence in the sample to a collection of known genomes. We take advantage of the combinatorial properties of an extension of the Burrows-Wheeler transform, and we sequentially scan the required data structures, so that we can analyze unknown sequences of large collections using little internal memory. The tool LiME (Lightweight Metagenomics via eBWT) is available at https://github.com/veronicaguerrini/LiME. Conclusions: In order to assess the reliability of our approach, we run several experiments on NGS data from two simulated metagenomes among those provided in benchmarking analysis and on a real metagenome from the Human Microbiome Project. The experiment results on the simulated data show that LiME is competitive with the widely used taxonomic classifiers. It achieves high levels of precision and specificity - e.g. 99.9% of the positive control reads are correctly assigned and the percentage of classified reads of the negative control is less than 0.01% - while keeping a high sensitivity. On the real metagenome, we show that LiME is able to deliver classification results comparable to that of MagicBlast. Overall, the experiments confirm the effectiveness of our method and its high accuracy even in negative control samples

Detecting Mutations by eBWT

In this paper we develop a theory describing how the extended Burrows-Wheeler Transform (EBWT) of a collection of DNA fragments tends to cluster together the copies of nucleotides sequenced from a genome G. Our theory accurately predicts how many copies of any nucleotide are expected inside each such cluster, and how an elegant and precise LCP array based procedure can locate these clusters in the EBWT. Our findings are very general and can be applied to a wide range of different problems. In this paper, we consider the case of alignment-free and reference-free SNPs discovery in multiple collections of reads. We note that, in accordance with our theoretical results, SNPs are clustered in the EBWT of the reads collection, and we develop a tool finding SNPs with a simple scan of the EBWT and LCP arrays. Preliminary results show that our method requires much less coverage than state-of-the-art tools while drastically improving precision and sensitivity

Prospects and limitations of full-text index structures in genome analysis

The combination of incessant advances in sequencing technology producing large amounts of data and innovative bioinformatics approaches, designed to cope with this data flood, has led to new interesting results in the life sciences. Given the magnitude of sequence data to be processed, many bioinformatics tools rely on efficient solutions to a variety of complex string problems. These solutions include fast heuristic algorithms and advanced data structures, generally referred to as index structures. Although the importance of index structures is generally known to the bioinformatics community, the design and potency of these data structures, as well as their properties and limitations, are less understood. Moreover, the last decade has seen a boom in the number of variant index structures featuring complex and diverse memory-time trade-offs. This article brings a comprehensive state-of-the-art overview of the most popular index structures and their recently developed variants. Their features, interrelationships, the trade-offs they impose, but also their practical limitations, are explained and compared

Faster External Memory LCP Array Construction

The suffix array, perhaps the most important data structure in modern string processing, needs to be augmented with the longest-common-prefix (LCP) array in many applications. Their construction is often a major bottleneck especially when the data is too big for internal memory. We describe two new algorithms for computing the LCP array from the suffix array in external memory. Experiments demonstrate that the new algorithms are about a factor of two faster than the fastest previous algorithm