The identification of homologous gene families across multiple genomes is a central task in bacterial pangenomics traditionally requiring computationally demanding all-against-all comparisons. PanDelos addresses this challenge with an alignment-free and parameter-free approach based on k-mer profiles, combining high speed, ease of use, and competitive accuracy with state-of-the-art methods. However, the increasing availability of genomic data requires tools that can scale efficiently to larger datasets. To address this need, we present PanDelos-plus, a fully parallel, gene-centric redesign of PanDelos. The algorithm parallelizes the most computationally intensive phases (Best Hit detection and Bidirectional Best Hit extraction) through data decomposition and a thread pool strategy, while employing lightweight data structures to reduce memory usage. Benchmarks on synthetic datasets show that PanDelos-plus achieves up to 14x faster execution and reduces memory usage by up to 96%, while maintaining accuracy. These improvements enable population-scale comparative genomics to be performed on standard multicore workstations, making large-scale bacterial pangenome analysis accessible for routine use in everyday research.

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