Alice: fast and haplotype-aware assembly of high-fidelity reads based on MSR sketching

Faure, R.; Hilaire, B.; Flot, J.-F.; Lavenier, D.

doi:10.1101/2025.09.29.679204

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bioRxiv · 10.1101/2025.09.29.679204

Alice: fast and haplotype-aware assembly of high-fidelity reads based on MSR sketching

Faure, R.·Hilaire, B.·Flot, J.-F.·Lavenier, D.

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Abstract

BackgroundLong-read metagenomic assembly is becoming a critical bottleneck in microbiome analysis, as deep sequencing generates massive datasets that existing methods struggle to assemble while maintaining strain resolution. ResultsWe present Alice, a lightweight long-read assembler that achieves orders-of-magnitude speedups through a new sequence sketching technique, MSR sketching, compatible with classical assembly methods. Alice assembles a 235 Gbp soil metagenome in 5 hours using only 84 GB RAM--a task that causes most competing methods to exhaust our computational resources (500 GB RAM and 7 days runtime). Across diverse benchmarks, Alice delivered strain-resolved assemblies an order of magnitude faster than state-of-the-art approaches, while producing the most complete assemblies in some cases. ConclusionsMSR sketching overcomes computational barriers in metagenomic assembly, enabling fast, memory-efficient strain-resolved analysis of massive datasets. While Alices assemblies were more fragmented than with other assemblers, this approach establishes a promising paradigm for scalable metagenomic analysis.

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Faure, R., Hilaire, B., Flot, J.-F., Lavenier, D.. 2025-09-30. Alice: fast and haplotype-aware assembly of high-fidelity reads based on MSR sketching. https://doi.org/10.1101/2025.09.29.679204

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