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1. 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.

    

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2. An incrementally updatable and scalable system for large-scale sequence search using the Bentley–Saxe transformation

   https://doi.org/10.1093/bioinformatics/btac142  

   Almodaresi, Fatemeh ; Khan, Jamshed ; Madaminov, Sergey ; Ferdman, Michael ; Johnson, Rob ; Pandey, Prashant ; Patro, Rob ; Boeva, ed., Valentina ( March 2022 , Bioinformatics)

   In the past few years, researchers have proposed numerous indexing schemes for searching large datasets of raw sequencing experiments. Most of these proposed indexes are approximate (i.e. with one-sided errors) in order to save space. Recently, researchers have published exact indexes—Mantis, VariMerge and Bifrost—that can serve as colored de Bruijn graph representations in addition to serving as k-mer indexes. This new type of index is promising because it has the potential to support more complex analyses than simple searches. However, in order to be useful as indexes for large and growing repositories of raw sequencing data, they must scale to thousands of experiments and support efficient insertion of new data.

   In this paper, we show how to build a scalable and updatable exact raw sequence-search index. Specifically, we extend Mantis using the Bentley–Saxe transformation to support efficient updates, called Dynamic Mantis. We demonstrate Dynamic Mantis’s scalability by constructing an index of ≈40K samples from SRA by adding samples one at a time to an initial index of 10K samples. Compared to VariMerge and Bifrost, Dynamic Mantis is more efficient in terms of index-construction time and memory, query time and memory and index size. In our benchmarks, VariMerge and Bifrost scaled to only 5K and 80 samples, respectively, while Dynamic Mantis scaled to more than 39K samples. Queries were over 24× faster in Mantis than in Bifrost (VariMerge does not immediately support general search queries we require). Dynamic Mantis indexes were about 2.5× smaller than Bifrost’s indexes and about half as big as VariMerge’s indexes.

   Dynamic Mantis implementation is available at https://github.com/splatlab/mantis/tree/mergeMSTs.

   Supplementary data are available at Bioinformatics online.

    

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3. The K-mer File Format: a standardized and compact disk representation of sets of k -mers

   https://doi.org/10.1093/bioinformatics/btac528  

   Dufresne, Yoann ; Lemane, Teo ; Marijon, Pierre ; Peterlongo, Pierre ; Rahman, Amatur ; Kokot, Marek ; Medvedev, Paul ; Deorowicz, Sebastian ; Chikhi, Rayan ; Birol, ed., Inanc ( July 2022 , Bioinformatics)

   Bioinformatics applications increasingly rely on ad hoc disk storage of k-mer sets, e.g. for de Bruijn graphs or alignment indexes. Here, we introduce the K-mer File Format as a general lossless framework for storing and manipulating k-mer sets, realizing space savings of 3–5× compared to other formats, and bringing interoperability across tools.

   Format specification, C++/Rust API, tools: https://github.com/Kmer-File-Format/.

   Supplementary data are available at Bioinformatics online.

    

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4. 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.

    

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5. Cuttlefish: fast, parallel and low-memory compaction of de Bruijn graphs from large-scale genome collections

   https://doi.org/10.1093/bioinformatics/btab309  

   Khan, Jamshed ; Patro, Rob ( July 2021 , Bioinformatics)

   null (Ed.)

   Abstract Motivation The construction of the compacted de Bruijn graph from collections of reference genomes is a task of increasing interest in genomic analyses. These graphs are increasingly used as sequence indices for short- and long-read alignment. Also, as we sequence and assemble a greater diversity of genomes, the colored compacted de Bruijn graph is being used more and more as the basis for efficient methods to perform comparative genomic analyses on these genomes. Therefore, time- and memory-efficient construction of the graph from reference sequences is an important problem. Results We introduce a new algorithm, implemented in the tool Cuttlefish, to construct the (colored) compacted de Bruijn graph from a collection of one or more genome references. Cuttlefish introduces a novel approach of modeling de Bruijn graph vertices as finite-state automata, and constrains these automata’s state-space to enable tracking their transitioning states with very low memory usage. Cuttlefish is also fast and highly parallelizable. Experimental results demonstrate that it scales much better than existing approaches, especially as the number and the scale of the input references grow. On a typical shared-memory machine, Cuttlefish constructed the graph for 100 human genomes in under 9 h, using ∼29 GB of memory. On 11 diverse conifer plant genomes, the compacted graph was constructed by Cuttlefish in under 9 h, using ∼84 GB of memory. The only other tool completing these tasks on the hardware took over 23 h using ∼126 GB of memory, and over 16 h using ∼289 GB of memory, respectively. Availability and implementation Cuttlefish is implemented in C++14, and is available under an open source license at https://github.com/COMBINE-lab/cuttlefish. Supplementary information Supplementary data are available at Bioinformatics online. 

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