RefLA: Efficient reference-guided genome assembly from long reads

Abstract High-quality de novo genome assembly from long reads remains computationally demanding, while fast assemblers often compromise on contiguity or accuracy. This trade-off between speed and assembly quality presents a persistent challenge in large-scale genomic studies. Fortunately, high-quality reference genomes are now available for a growing number of species. These references can be leveraged to assist the assembly of closely related genomes, enabling efficient reconstruction without sacrificing fidelity—particularly when evolutionary divergence is moderate.We present RefLA, a reference-assisted assembler tailored for thirdgeneration long-read data. By combining alignment-guided structural refinement with localized reassembly, RefLA achieves accuracy comparable to or better than state-of-the-art de novo tools such as Flye and hifiasm, while running significantly faster. It also surpasses rapid assemblers like wtdbg2 and Shasta in both contiguity and base-level correctness. Competing Interest Statement The authors have declared no competing interest.