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bioRxiv · 10.1101/2024.02.15.580432

Phasing Diploid Genome Assembly Graphs with Single-Cell Strand Sequencing

Henglin, M.·Ghareghani, M.·Harvey, W.·Porubsky, D.·Koren, S.·Eichler, E. E.·Ebert, P.·Marschall, T.
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Abstract

Haplotype information is crucial for biomedical and population genetics research. However, current strategies to produce de-novo haplotype-resolved assemblies often require either difficult-to-acquire parental data or an intermediate haplotype-collapsed assembly. Here, we present Graphasing, a workflow which synthesizes the global phase signal of Strand-seq with assembly graph topology to produce chromosome-scale de-novo haplotypes for diploid genomes. Graphasing readily integrates with any assembly workflow that both outputs an assembly graph and has a haplotype assembly mode. Graphasing performs comparably to trio-phasing in contiguity, phasing accuracy, and assembly quality, outperforms Hi-C in phasing accuracy, and generates human assemblies with over 18 chromosome-spanning haplotypes.

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Henglin, M., Ghareghani, M., Harvey, W., Porubsky, D., Koren, S., Eichler, E. E., Ebert, P., Marschall, T.. 2024-02-16. Phasing Diploid Genome Assembly Graphs with Single-Cell Strand Sequencing. https://doi.org/10.1101/2024.02.15.580432

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