b-move: faster bidirectional character extensions in a run-length compressed index.

Due to the increasing availability of high-quality genome sequences, pan-genomes are gradually replacing single consensus reference genomes in many bioinformatics pipelines to better capture genetic diversity. Traditional bioinformatics tools using the FM-index face memory limitations with such large genome collections. Recent advancements in run-length compressed indices like Gagie et al.'s r-index and Nishimoto and Tabei's move structure, alleviate memory constraints but focus primarily on backward search for MEM-finding. Arakawa et al.'s br-index initiates complete approximate pattern matching using bidirectional search in run-length compressed space, but with significant computational overhead due to complex memory access patterns. We introduce b-move, a novel bidirectional extension of the move structure, enabling fast, cache-efficient bidirectional character extensions in run-length compressed space. It achieves bidirectional character extensions up to 8 times faster than the br-index, closing the performance gap with FM-index-based alternatives, while maintaining the br-index's favorable memory characteristics. For example, all available complete E. coli genomes on NCBI's RefSeq collection can be compiled into a b-move index that fits into the RAM of a typical laptop. Thus, b-move proves practical and scalable for pan-genome indexing and querying. We provide a C++ implementation of b-move, supporting efficient lossless approximate pattern matching including locate functionality, available at https://github.com/biointec/b-move under the AGPL-3.0 license.

Pan-genome de Bruijn graph using the bidirectional FM-index.

BACKGROUND: Pan-genome graphs are gaining importance in the field of bioinformatics as data structures to represent and jointly analyze multiple genomes. Compacted de Bruijn graphs are inherently suited for this purpose, as their graph topology naturally reveals similarity and divergence within the pan-genome. Most state-of-the-art pan-genome graphs are represented explicitly in terms of nodes and edges. Recently, an alternative, implicit graph representation was proposed that builds directly upon the unidirectional FM-index. As such, a memory-efficient graph data structure is obtained that inherits the FM-index' backward search functionality. However, this representation suffers from a number of shortcomings in terms of functionality and algorithmic performance. RESULTS: We present a data structure for a pan-genome, compacted de Bruijn graph that aims to address these shortcomings. It is built on the bidirectional FM-index, extending the ability of its unidirectional counterpart to navigate and search the graph in both directions. All basic graph navigation steps can be performed in constant time. Based on these features, we implement subgraph visualization as well as lossless approximate pattern matching to the graph using search schemes. We demonstrate that we can retrieve all occurrences corresponding to a read within a certain edit distance in a very efficient manner. Through a case study, we show the potential of exploiting the information embedded in the graph's topology through visualization and sequence alignment. CONCLUSIONS: We propose a memory-efficient representation of the pan-genome graph that supports subgraph visualization and lossless approximate pattern matching of reads against the graph using search schemes. The C++ source code of our software, called Nexus, is available at https://github.com/biointec/nexus under AGPL-3.0 license.

Dynamic partitioning of search patterns for approximate pattern matching using search schemes.

Search schemes constitute a flexible and generic framework to describe how all approximate occurrences of a search pattern in a text can be found efficiently. We propose an algorithm for the dynamic partitioning of search patterns which can be universally applied to any kind of search scheme and demonstrate that this technique significantly reduces the search space. We present Columba, a software tool written in C++, in which a multitude of search schemes are implemented. We discuss implementation aspects such as memory interleaving of Burrows-Wheeler transform representations and the reduction of redundancy that is inherently associated with the edit distance metric. Ultimately, we demonstrate that Columba has superior performance to the state of the art. Using a single CPU core, Columba is able to retrieve all occurrences of 100,000 Illumina reads and their reverse complements within a maximum edit distance of four in the human genome in less than 3 min.