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Generating pangenomic datasets is becoming increasingly common but there are still few tools able to handle them and even fewer accessible to non-specialists. Building compressed suffix trees (CSTs) for pangenomic datasets is still a major challenge but could be enor- mously beneficial to the community. In this paper, we present a method, which we refer to as RePFP-CST, for building CSTs in a manner that is scalable. To accomplish this, we show how to build a CST directly from VCF files without decompressing them, and to prune from the prefix-free parse (PFP) phrase boundaries whose removal reduces the total size of the dictionary and the parse. We show that these improvements reduce the time and space required for the construction of the CST, and the memory footprint of the finished CST, enabling us to build a CST for a terabyte of DNA for the first time in the literature.

Abstract Computational pangenomics is an emerging research field that is changing the way computer scientists are facing challenges in biological sequence analysis. In past decades, contributions from combinatorics, stringology, graph theory and data structures were essential in the development of a plethora of software tools for the analysis of the human genome. These tools allowed computational biologists to approach ambitious projects at population scale, such as the 1000 Genomes Project. A major contribution of the 1000 Genomes Project is the characterization of a broad spectrum of genetic variations in the human genome, including the discovery of novel variations in the South Asian, African and European populations—thus enhancing the catalogue of variability within the reference genome. Currently, the need to take into account the high variability in population genomes as well as the specificity of an individual genome in a personalized approach to medicine is rapidly pushing the abandonment of the traditional paradigm of using a single reference genome. A graph-based representation of multiple genomes, or a graph pangenome , is replacing the linear reference genome. This means completely rethinking well-established procedures to analyze, store, and access information from genome representations. Properly addressing these challenges is crucial to face the computationalmore »tasks of ambitious healthcare projects aiming to characterize human diversity by sequencing 1M individuals (Stark et al. 2019). This tutorial aims to introduce readers to the most recent advances in the theory of data structures for the representation of graph pangenomes. We discuss efficient representations of haplotypes and the variability of genotypes in graph pangenomes, and highlight applications in solving computational problems in human and microbial (viral) pangenomes.« less

Large sequencing projects, such as GenomeTrakr and MetaSub, are updated frequently (sometimes daily, in the case of GenomeTrakr) with new data. Therefore, it is imperative that any data structure indexing such data supports efficient updates. Toward this goal, Bannai et al. (TCS, 2020) proposed a data structure named dynamic r-index which is suitable for large genome collections and supports incremental construction; however, it is still not powerful enough to support substantial updates. Here, we develop a novel algorithm for updating the r-index, which we refer to as RIMERGE. Fundamental to our algorithm is the combination of the basics of the dynamic r-index with a known algorithm for merging Burrows-Wheeler Transforms (BWTs). As a result, RIMERGE is capable of performing batch updates in a manner that exploits parallelism while keeping the memory overhead small. We compare our method to the dynamic r-index of Bannai et al. using two different datasets, and show that RIMERGE is between 1.88 to 5.34 times faster on reasonably large inputs.

Grammar compression is, next to Lempel-Ziv (LZ77) and run-length Burrows-Wheeler transform (RLBWT), one of the most flexible approaches to representing and processing highly compressible strings. The main idea is to represent a text as a context-free grammar whose language is precisely the input string. This is called a straight-line grammar (SLG). An AVL grammar, proposed by Rytter [Theor. Comput. Sci., 2003] is a type of SLG that additionally satisfies the AVL property: the heights of parse trees for children of every nonterminal differ by at most one. In contrast to other SLG constructions, AVL grammars can be constructed from the LZ77 parsing in compressed time: 𝒪(z log n) where z is the size of the LZ77 parsing and n is the length of the input text. Despite these advantages, AVL grammars are thought to be too large to be practical. We present a new technique for rapidly constructing a small AVL grammar from an LZ77 or LZ77-like parse. Our algorithm produces grammars that are always at least five times smaller than those produced by the original algorithm, and usually not more than double the size of grammars produced by the practical Re-Pair compressor [Larsson and Moffat, Proc. IEEE, 2000]. Ourmore »algorithm also achieves low peak RAM usage. By combining this algorithm with recent advances in approximating the LZ77 parsing, we show that our method has the potential to construct a run-length BWT in about one third of the time and peak RAM required by other approaches. Overall, we show that AVL grammars are surprisingly practical, opening the door to much faster construction of key compressed data structures« less

Compressed full-text indexes are one of the main success stories of bioinformatics data structures but even they struggle to handle some DNA readsets. This may seem surprising since, at least when dealing with short reads from the same individual, the readset will be highly repetitive and, thus, highly compressible. If we are not careful, however, this advantage can be more than offset by two disadvantages: first, since most base pairs are included in at least tens reads each, the uncompressed readset is likely to be at least an order of magnitude larger than the individual’s uncompressed genome; second, these indexes usually pay some space overhead for each string they store, and the total overhead can be substantial when dealing with millions of reads. The most successful compressed full-text indexes for readsets so far are based on the Extended Burrows-Wheeler Transform (EBWT) and use a sorting heuristic to try to reduce the space overhead per read, but they still treat the reads as separate strings and thus may not take full advantage of the readset’s structure. For example, if we have already assembled an individual’s genome from the readset, then we can usually use it to compress the readset well: e.g.,more »we store the gap-coded list of reads’ starting positions; we store the list of their lengths, which is often highly compressible; and we store information about the sequencing errors, which are rare with short reads. There is nowhere, however, where we can plug an assembled genome into the EBWT. In this paper we show how to use one or more assembled or partially assembled genome as the basis for a compressed full-text index of its readset. Specifically, we build a labelled tree by taking the assembled genome as a trunk and grafting onto it the reads that align to it, at the starting positions of their alignments. Next, we compute the eXtended Burrows-Wheeler Transform (XBWT) of the resulting labelled tree and build a compressed full-text index on that. Although this index can occasionally return false positives, it is usually much more compact than the alternatives. Following the established practice for datasets with many repetitions, we compare different full-text indices by looking at the number of runs in the transformed strings. For a human Chr19 readset our preliminary experiments show that eliminating separators characters from the EBWT reduces the number of runs by 19%, from 220 million to 178 million, and using the XBWT reduces it by a further 15%, to 150 million.« less

We extend recent results regarding finding shortest unique substrings (SUSs) to obtain new time-space tradeoffs for this problem and the generalization of finding k-mismatch SUSs. Our new results include the first algorithm for finding a k-mismatch SUS in sublinear space, which we obtain by extending an algorithm by Senanayaka (2019) and combining it with a result on sketching by Gawrychowski and Starikovskaya (2019). We first describe how, given a text T of length n and m words of workspace, with high probability we can find an SUS of length L in O(n(L/m)logL) time using random access to T, or in O(n(L/m)log2(L)loglogσ) time using O((L/m)log2L) sequential passes over T. We then describe how, for constant k, with high probability, we can find a k-mismatch SUS in O(n1+ϵL/m) time using O(nϵL/m) sequential passes over T, again using only m words of workspace. Finally, we also describe a deterministic algorithm that takes O(nτlogσlogn) time to find an SUS using O(n/τ) words of workspace, where τ is a parameter.