Fast and Scalable Parallel External-Memory Construction of Colored Compacted de Bruijn Graphs with Cuttlefish 3

The exponential growth of genomic data has created an urgent need for scalable sequence analysis algorithms. De Bruijn graphs--along with their colored and compacted variants--have become essential tools in modern bioinformatics pipelines. Colored compacted de Bruijn graphs condense repetitive sequence information, significantly reducing the data burden on downstream analyses like genome assembly, metagenomic clustering, and pan-genomics. Since constructing uncompacted graphs becomes computationally prohibitive at scale, direct construction methods for colored compacted de Bruijn graphs are essential for the scalability of downstream analyses. We present Cuttlefish 3, a parallel external-memory algorithm that delivers state-of-the-art performance for constructing colored compacted de Bruijn graphs. Our approach introduces three algorithmic innovations that enable efficient scaling to massive datasets while maintaining high performance. First, we develop an optimized technique for accelerating local subgraph contractions. Second, we design a deterministic parallel algorithm based on list-ranking to efficiently merge local solutions. Third, we introduce a novel combinable hash-based method for identifying and tracking color-changing nodes, enabling rapid color-set extraction. We evaluate Cuttlefish 3 on diverse large-scale genomic datasets. In our benchmarks, Cuttlefish 3 achieves 3.29-4.09x speedup over GGCAT, the current state-of-the-art tool, while maintaining comparable memory usage. These performance gains make Cuttlefish 3 a practical solution for representing and analyzing the growing volumes of genomic data in modern bioinformatics workflows. Cuttlefish 3 is implemented in C++17 and is available at https://github.com/COMBINE-lab/cuttlefish.