Graphasing: phasing diploid genome assembly graphs with single-cell strand sequencing
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.
Authors
- Evan E. Eichler (ORCID: https://orcid.org/0000-0002-8246-4014)
- Sergey Koren (ORCID: https://orcid.org/0000-0002-1472-8962)
- William T. Harvey (ORCID: https://orcid.org/0000-0003-0646-7528)
- Mir Henglin (ORCID: https://orcid.org/0000-0003-3604-4868)
- Peter Ebert (ORCID: https://orcid.org/0000-0001-7441-532X)
- Maryam Ghareghani
- Tobias Marschall (ORCID: https://orcid.org/0000-0002-9376-1030)
- David Porubský (ORCID: https://orcid.org/0000-0001-8414-8966)
Institutions
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- University of Washington (US)
- Düsseldorf University Hospital (DE)
- National Human Genome Research Institute (US)
- Max Planck Institute for Molecular Genetics (DE)
- Heinrich Heine University Düsseldorf (DE)
- Freie Universität Berlin (DE)
Publication Details
- Journal
- Genome biology
- Published
- 2024-10-10
- DOI
- https://doi.org/10.1186/s13059-024-03409-1
- Citations
- 10
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 6.00
Funders
- University of California, Santa Cruz