More Like this

1. μ- PBWT: a lightweight r-indexing of the PBWT for storing and querying UK Biobank data

   https://doi.org/10.1093/bioinformatics/btad552  

   Cozzi, Davide ; Rossi, Massimiliano ; Rubinacci, Simone ; Gagie, Travis ; Köppl, Dominik ; Boucher, Christina ; Bonizzoni, Paola ; Robinson, ed., Peter ( September 2023 , Bioinformatics)

   The Positional Burrows–Wheeler Transform (PBWT) is a data structure that indexes haplotype sequences in a manner that enables finding maximal haplotype matches in h sequences containing w variation sites in O(hw) time. This represents a significant improvement over classical quadratic-time approaches. However, the original PBWT data structure does not allow for queries over Biobank panels that consist of several millions of haplotypes, if an index of the haplotypes must be kept entirely in memory.

   In this article, we leverage the notion of r-index proposed for the BWT to present a memory-efficient method for constructing and storing the run-length encoded PBWT, and computing set maximal matches (SMEMs) queries in haplotype sequences. We implement our method, which we refer to as μ-PBWT, and evaluate it on datasets of 1000 Genome Project and UK Biobank data. Our experiments demonstrate that the μ-PBWT reduces the memory usage up to a factor of 20% compared to the best current PBWT-based indexing. In particular, μ-PBWT produces an index that stores high-coverage whole genome sequencing data of chromosome 20 in about a third of the space of its BCF file. μ-PBWT is an adaptation of techniques for the run-length compressed BWT for the PBWT (RLPBWT) and it is based on keeping in memory only a succinct representation of the RLPBWT that still allows the efficient computation of set maximal matches (SMEMs) over the original panel.

   Our implementation is open source and available at https://github.com/dlcgold/muPBWT. The binary is available at https://bioconda.github.io/recipes/mupbwt/README.html.

    

   more » « less
2. Optimal gap-affine alignment in O ( s ) space

   https://doi.org/10.1093/bioinformatics/btad074  

   Marco-Sola, Santiago ; Eizenga, Jordan M ; Guarracino, Andrea ; Paten, Benedict ; Garrison, Erik ; Moreto, Miquel ( February 2023 , Bioinformatics)

   Martelli, Pier Luigi (Ed.)

   Pairwise sequence alignment remains a fundamental problem in computational biology and bioinformatics. Recent advances in genomics and sequencing technologies demand faster and scalable algorithms that can cope with the ever-increasing sequence lengths. Classical pairwise alignment algorithms based on dynamic programming are strongly limited by quadratic requirements in time and memory. The recently proposed wavefront alignment algorithm (WFA) introduced an efficient algorithm to perform exact gap-affine alignment in O(ns) time, where s is the optimal score and n is the sequence length. Notwithstanding these bounds, WFA’s O(s2) memory requirements become computationally impractical for genome-scale alignments, leading to a need for further improvement.

   In this article, we present the bidirectional WFA algorithm, the first gap-affine algorithm capable of computing optimal alignments in O(s) memory while retaining WFA’s time complexity of O(ns). As a result, this work improves the lowest known memory bound O(n) to compute gap-affine alignments. In practice, our implementation never requires more than a few hundred MBs aligning noisy Oxford Nanopore Technologies reads up to 1 Mbp long while maintaining competitive execution times.

   All code is publicly available at https://github.com/smarco/BiWFA-paper.

   Supplementary data are available at Bioinformatics online.

    

   more » « less
3. Practical dynamic de Bruijn graphs

   https://doi.org/10.1093/bioinformatics/bty500  

   Crawford, Victoria G. ; Kuhnle, Alan ; Boucher, Christina ; Chikhi, Rayan ; Gagie, Travis ; Hancock, ed., John ( June 2018 , Bioinformatics)

   The de Bruijn graph is fundamental to the analysis of next generation sequencing data and so, as datasets of DNA reads grow rapidly, it becomes more important to represent de Bruijn graphs compactly while still supporting fast assembly. Previous implementations of compact de Bruijn graphs have not supported node or edge deletion, however, which is important for pruning spurious elements from the graph.

   Belazzougui et al. (2016b) recently proposed a compact and fully dynamic representation, which supports exact membership queries and insertions and deletions of both nodes and edges. In this paper, we give a practical implementation of their data structure, supporting exact membership queries and fully dynamic edge operations, as well as limited support for dynamic node operations. We demonstrate experimentally that its performance is comparable to that of state-of-the-art implementations based on Bloom filters.

   Our source-code is publicly available at https://github.com/csirac/dynamicDBG under an open-source license.

    

   more » « less
4. HyGraph: a subgraph isomorphism algorithm for efficiently querying big graph databases

   https://doi.org/10.1186/s40537-022-00589-0  

   Asiler, Merve ; Yazıcı, Adnan ; George, Roy ( April 2022 , Journal of Big Data)

   The big graph database provides strong modeling capabilities and efficient querying for complex applications. Subgraph isomorphism which finds exact matches of a query graph in the database efficiently, is a challenging problem. Current subgraph isomorphism approaches mostly are based on the pruning strategy proposed by Ullmann. These techniques have two significant drawbacks- first, they are unable to efficiently handle complex queries, and second, their implementations need the large indexes that require large memory resources. In this paper, we describe a new subgraph isomorphism approach, the HyGraph algorithm, that is efficient both in querying and with memory requirements for index creation. We compare the HyGraph algorithm with two popular existing approaches, GraphQL and Cypher using complexity measures and experimentally using three big graph data sets—(1) a country-level population database, (2) a simulated bank database, and (3) a publicly available World Cup big graph database. It is shown that the HyGraph solution performs significantly better (or equally) than competing algorithms for the query operations on these big databases, making it an excellent candidate for subgraph isomorphism queries in real scenarios.

    

   more » « less
5. A space and time-efficient index for the compacted colored de Bruijn graph

   https://doi.org/10.1093/bioinformatics/bty292  

   Almodaresi, Fatemeh ; Sarkar, Hirak ; Srivastava, Avi ; Patro, Rob ( June 2018 , Bioinformatics)

   Indexing reference sequences for search—both individual genomes and collections of genomes—is an important building block for many sequence analysis tasks. Much work has been dedicated to developing full-text indices for genomic sequences, based on data structures such as the suffix array, the BWT and the FM-index. However, the de Bruijn graph, commonly used for sequence assembly, has recently been gaining attention as an indexing data structure, due to its natural ability to represent multiple references using a graphical structure, and to collapse highly-repetitive sequence regions. Yet, much less attention has been given as to how to best index such a structure, such that queries can be performed efficiently and memory usage remains practical as the size and number of reference sequences being indexed grows large.

   We present a novel data structure for representing and indexing the compacted colored de Bruijn graph, which allows for efficient pattern matching and retrieval of the reference information associated with each k-mer. As the popularity of the de Bruijn graph as an index has increased over the past few years, so have the number of proposed representations of this structure. Existing structures typically fall into two categories; those that are hashing-based and provide very fast access to the underlying k-mer information, and those that are space-frugal and provide asymptotically efficient but practically slower pattern search. Our representation achieves a compromise between these two extremes. By building upon minimum perfect hashing and making use of succinct representations where applicable, our data structure provides practically fast lookup while greatly reducing the space compared to traditional hashing-based implementations. Further, we describe a sampling scheme for this index, which provides the ability to trade off query speed for a reduction in the index size. We believe this representation strikes a desirable balance between speed and space usage, and allows for fast search on large reference sequences.

   Finally, we describe an application of this index to the taxonomic read assignment problem. We show that by adopting, essentially, the approach of Kraken, but replacing k-mer presence with coverage by chains of consistent unique maximal matches, we can improve the space, speed and accuracy of taxonomic read assignment.

   pufferfish is written in C++11, is open source, and is available at https://github.com/COMBINE-lab/pufferfish.

   Supplementary data are available at Bioinformatics online.

    

   more » « less