Computing matching statistics on Wheeler DFAs.

Matching statistics were introduced to solve the approximate string matching problem, which is a recurrent subroutine in bioinformatics applications. In 2010, Ohlebusch et al. [SPIRE 2010] proposed a time and space efficient algorithm for computing matching statistics which relies on some components of a compressed suffix tree - notably, the longest common prefix (LCP) array. In this paper, we show how their algorithm can be generalized from strings to Wheeler deterministic finite automata. Most importantly, we introduce a notion of LCP array for Wheeler automata, thus establishing a first clear step towards extending (compressed) suffix tree functionalities to labeled graphs.

r-indexing the eBWT.

The extended Burrows Wheeler Transform (eBWT) was introduced by Mantaci et al. [TCS 2007] to extend the definition of the BWT to a collection of strings. In our prior work [SPIRE 2021], we give a linear-time algorithm for the eBWT that preserves the fundamental property of the original definition (i.e., the independence from the input order). The algorithm combines a modification of the Suffix Array Induced Sorting (SAIS) algorithm [IEEE Trans Comput 2011] with Prefix Free Parsing [AMB 2019; JCB 2020]. In this paper, we show how this construction algorithm leads to r-indexing the eBWT, i.e., run-length encoded eBWT and SA samples of Gagie et al. [SODA 2018] can be constructed efficiently from the components of the PFP. Moreover, we show that finding maximal exact matches (MEMs) between a query string and the r-index of the eBWT can be efficiently supported.

Computing the original eBWT faster, simpler, and with less memory.

Given an input string, the Burrows-Wheeler Transform (BWT) can be seen as a reversible permutation of it that allows efficient compression and fast substring queries. Due to these properties, it has been widely applied in the analysis of genomic sequence data, enabling important tasks such as read alignment. Mantaci et al. [TCS2007] extended the notion of the BWT to a collection of strings by defining the extended Burrows-Wheeler Transform (eBWT). This definition requires no modification of the input collection, and has the property that the output is independent of the order of the strings in the collection. However, over the years, the term eBWT has been used more generally to describe any BWT of a collection of strings. The fundamental property of the original definition (i.e., the independence from the input order) is frequently disregarded. In this paper, we propose a simple linear-time algorithm for the construction of the original eBWT, which does not require the preprocessing of Bannai et al. [CPM 2021]. As a byproduct, we obtain the first linear-time algorithm for computing the BWT of a single string that uses neither an end-of-string symbol nor Lyndon rotations. We also combine our new eBWT construction with a variation of prefix-free parsing (PFP) [WABI 2019] to allow for construction of the eBWT on large collections of genomic sequences. We implement this combined algorithm (pfpebwt) and evaluate it on a collection of human chromosomes 19 from the 1,000 Genomes Project, on a collection of Salmonella genomes from GenomeTrakr, and on a collection of SARS-CoV2 genomes from EBI's COVID-19 data portal. We demonstrate that pfpebwt is the fastest method for all collections, with a maximum speedup of 7.6x on the second best method. The peak memory is at most 2x larger than the second best method. Comparing with methods that are also, as our algorithm, able to report suffix array samples, we obtain a 57.1x improvement in peak memory. The source code is publicly available at https://github.com/davidecenzato/PFP-eBWT.

Variable-order reference-free variant discovery with the Burrows-Wheeler Transform.

BACKGROUND: In [Prezza et al., AMB 2019], a new reference-free and alignment-free framework for the detection of SNPs was suggested and tested. The framework, based on the Burrows-Wheeler Transform (BWT), significantly improves sensitivity and precision of previous de Bruijn graphs based tools by overcoming several of their limitations, namely: (i) the need to establish a fixed value, usually small, for the order k, (ii) the loss of important information such as k-mer coverage and adjacency of k-mers within the same read, and (iii) bad performance in repeated regions longer than k bases. The preliminary tool, however, was able to identify only SNPs and it was too slow and memory consuming due to the use of additional heavy data structures (namely, the Suffix and LCP arrays), besides the BWT. RESULTS: In this paper, we introduce a new algorithm and the corresponding tool ebwt2InDel that (i) extend the framework of [Prezza et al., AMB 2019] to detect also INDELs, and (ii) implements recent algorithmic findings that allow to perform the whole analysis using just the BWT, thus reducing the working space by one order of magnitude and allowing the analysis of full genomes. Finally, we describe a simple strategy for effectively parallelizing our tool for SNP detection only. On a 24-cores machine, the parallel version of our tool is one order of magnitude faster than the sequential one. The tool ebwt2InDel is available at github.com/nicolaprezza/ebwt2InDel . CONCLUSIONS: Results on a synthetic dataset covered at 30x (Human chromosome 1) show that our tool is indeed able to find up to 83% of the SNPs and 72% of the existing INDELs. These percentages considerably improve the 71% of SNPs and 51% of INDELs found by the state-of-the art tool based on de Bruijn graphs. We furthermore report results on larger (real) Human whole-genome sequencing experiments. Also in these cases, our tool exhibits a much higher sensitivity than the state-of-the art tool.

SNPs detection by eBWT positional clustering.

BACKGROUND: Sequencing technologies keep on turning cheaper and faster, thus putting a growing pressure for data structures designed to efficiently store raw data, and possibly perform analysis therein. In this view, there is a growing interest in alignment-free and reference-free variants calling methods that only make use of (suitably indexed) raw reads data. RESULTS: We develop the positional clustering theory that (i) describes how the extended Burrows-Wheeler Transform (eBWT) of a collection of reads tends to cluster together bases that cover the same genome position (ii) predicts the size of such clusters, and (iii) exhibits an elegant and precise LCP array based procedure to locate such clusters in the eBWT. Based on this theory, we designed and implemented an alignment-free and reference-free SNPs calling method, and we devised a consequent SNPs calling pipeline. Experiments on both synthetic and real data show that SNPs can be detected with a simple scan of the eBWT and LCP arrays as, in accordance with our theoretical framework, they are within clusters in the eBWT of the reads. Finally, our tool intrinsically performs a reference-free evaluation of its accuracy by returning the coverage of each SNP. CONCLUSIONS: Based on the results of the experiments on synthetic and real data, we conclude that the positional clustering framework can be effectively used for the problem of identifying SNPs, and it appears to be a promising approach for calling other type of variants directly on raw sequencing data. AVAILABILITY: The software ebwt2snp is freely available for academic use at: https://github.com/nicolaprezza/ebwt2snp.