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1. 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 (September 2022, Bioinformatics)

   Birol, Inanc (Ed.)

   Abstract Summary 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. Availability and implementation Format specification, C++/Rust API, tools: https://github.com/Kmer-File-Format/. Supplementary information Supplementary data are available at Bioinformatics online. 

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2. Practical selection of representative sets of RNA-seq samples using a hierarchical approach

   https://doi.org/10.1093/bioinformatics/btab315  

   Tung, Laura H; Kingsford, Carl (July 2021, Bioinformatics)

   Abstract Motivation Despite numerous RNA-seq samples available at large databases, most RNA-seq analysis tools are evaluated on a limited number of RNA-seq samples. This drives a need for methods to select a representative subset from all available RNA-seq samples to facilitate comprehensive, unbiased evaluation of bioinformatics tools. In sequence-based approaches for representative set selection (e.g. a k-mer counting approach that selects a subset based on k-mer similarities between RNA-seq samples), because of the large numbers of available RNA-seq samples and of k-mers/sequences in each sample, computing the full similarity matrix using k-mers/sequences for the entire set of RNA-seq samples in a large database (e.g. the SRA) has memory and runtime challenges; this makes direct representative set selection infeasible with limited computing resources. Results We developed a novel computational method called ‘hierarchical representative set selection’ to handle this challenge. Hierarchical representative set selection is a divide-and-conquer-like algorithm that breaks representative set selection into sub-selections and hierarchically selects representative samples through multiple levels. We demonstrate that hierarchical representative set selection can achieve summarization quality close to that of direct representative set selection, while largely reducing runtime and memory requirements of computing the full similarity matrix (up to 8.4× runtime reduction and 5.35× memory reduction for 10 000 and 12 000 samples respectively that could be practically run with direct subset selection). We show that hierarchical representative set selection substantially outperforms random sampling on the entire SRA set of RNA-seq samples, making it a practical solution to representative set selection on large databases like the SRA. Availability and implementation The code is available at https://github.com/Kingsford-Group/hierrepsetselection and https://github.com/Kingsford-Group/jellyfishsim. Supplementary information Supplementary data are available at Bioinformatics online. 

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3. eCAMI: simultaneous classification and motif identification for enzyme annotation

   https://doi.org/10.1093/bioinformatics/btz908  

   Xu, Jing; Zhang, Han; Zheng, Jinfang; Dovoedo, Philippe; Yin, Yanbin; Xu, Jinbo (December 2019, Bioinformatics)

   Abstract Motivation Carbohydrate-active enzymes (CAZymes) are extremely important to bioenergy, human gut microbiome, and plant pathogen researches and industries. Here we developed a new amino acid k-mer-based CAZyme classification, motif identification and genome annotation tool using a bipartite network algorithm. Using this tool, we classified 390 CAZyme families into thousands of subfamilies each with distinguishing k-mer peptides. These k-mers represented the characteristic motifs (in the form of a collection of conserved short peptides) of each subfamily, and thus were further used to annotate new genomes for CAZymes. This idea was also generalized to extract characteristic k-mer peptides for all the Swiss-Prot enzymes classified by the EC (enzyme commission) numbers and applied to enzyme EC prediction. Results This new tool was implemented as a Python package named eCAMI. Benchmark analysis of eCAMI against the state-of-the-art tools on CAZyme and enzyme EC datasets found that: (i) eCAMI has the best performance in terms of accuracy and memory use for CAZyme and enzyme EC classification and annotation; (ii) the k-mer-based tools (including PPR-Hotpep, CUPP and eCAMI) perform better than homology-based tools and deep-learning tools in enzyme EC prediction. Lastly, we confirmed that the k-mer-based tools have the unique ability to identify the characteristic k-mer peptides in the predicted enzymes. Availability and implementation https://github.com/yinlabniu/eCAMI and https://github.com/zhanglabNKU/eCAMI. Supplementary information Supplementary data are available at Bioinformatics online. 

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4. On the Maximal Independent Sets of k-mers with the Edit Distance

   https://doi.org/10.1145/3584371.3612982  

   Ma, Leran; Chen, Ke; Shao, Mingfu (September 2023, Proceedings of the 14th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics)

   In computational biology, k-mers and edit distance are fundamental concepts. However, little is known about the metric space of all k-mers equipped with the edit distance. In this work, we explore the structure of the k-mer space by studying its maximal independent sets (MISs). An MIS is a sparse sketch of all k-mers with nice theoretical properties, and therefore admits critical applications in clustering, indexing, hashing, and sketching large-scale sequencing data, particularly those with high error-rates. Finding an MIS is a challenging problem, as the size of a k-mer space grows geometrically with respect to k. We propose three algorithms for this problem. The first and the most intuitive one uses a greedy strategy. The second method implements two techniques to avoid redundant comparisons by taking advantage of the locality-property of the k-mer space and the estimated bounds on the edit distance. The last algorithm avoids expensive calculations of the edit distance by translating the edit distance into the shortest path in a specifically designed graph. These algorithms are implemented and the calculated MISs of k-mer spaces and their statistical properties are reported and analyzed for k up to 15. Source code is freely available at https://github.com/Shao-Group/kmerspace. 

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5. Genome-wide alignment-free phylogenetic distance estimation under a no strand-bias model

   https://doi.org/10.1093/bioadv/vbac055  

   Balaban, Metin; Bristy, Nishat Anjum; Faisal, Ahnaf; Bayzid, Md Shamsuzzoha; Mirarab, Siavash (January 2022, Bioinformatics Advances)

   Lengauer, Thomas (Ed.)

   Abstract   Summary: While alignment has been the dominant approach for determining homology prior to phylogenetic inference, alignment-free methods can simplify the analysis, especially when analyzing genome-wide data. Furthermore, alignment-free methods present the only option for emerging forms of data, such as genome skims, which do not permit assembly. Despite the appeal, alignment-free methods have not been competitive with alignment-based methods in terms of accuracy. One limitation of alignment-free methods is their reliance on simplified models of sequence evolution such as Jukes–Cantor. If we can estimate frequencies of base substitutions in an alignment-free setting, we can compute pairwise distances under more complex models. However, since the strand of DNA sequences is unknown for many forms of genome-wide data, which arguably present the best use case for alignment-free methods, the most complex models that one can use are the so-called no strand-bias models. We show how to calculate distances under a four-parameter no strand-bias model called TK4 without relying on alignments or assemblies. The main idea is to replace letters in the input sequences and recompute Jaccard indices between k-mer sets. However, on larger genomes, we also need to compute the number of k-mer mismatches after replacement due to random chance as opposed to homology. We show in simulation that alignment-free distances can be highly accurate when genomes evolve under the assumed models and study the accuracy on assembled and unassembled biological data. Availability and implementation Our software is available open source at https://github.com/nishatbristy007/NSB. Supplementary information Supplementary data are available at Bioinformatics Advances online. 

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