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bioRxiv · 10.1101/271486

Complete assembly of parental haplotypes with trio binning

Koren, S.·Rhie, A.·Walenz, B. P.·Dilthey, A. T.·Bickhart, D. M.·Kingan, S. B.·Hiendleder, S.·Williams, J. L.·Smith, T. P. L.·Phillippy, A.
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Abstract

Reference genome projects have historically selected inbred individuals to minimize heterozygosity and simplify assembly. We challenge this dogma and present a new approach designed specifically for heterozygous genomes. \"Trio binning\" uses short reads from two parental genomes to partition long reads from an offspring into haplotype-specific sets prior to assembly. Each haplotype is then assembled independently, resulting in a complete diploid reconstruction. On a benchmark human trio, this method achieved high accuracy and recovered complex structural variants missed by alternative approaches. To demonstrate its effectiveness on a heterozygous genome, we sequenced an F1 cross between cattle subspecies Bos taurus taurus and Bos taurus indicus, and completely assembled both parental haplotypes with NG50 haplotig sizes >20 Mbp and 99.998% accuracy, surpassing the quality of current cattle reference genomes. We propose trio binning as a new best practice for diploid genome assembly that will enable new studies of haplotype variation and inheritance.

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Koren, S., Rhie, A., Walenz, B. P., Dilthey, A. T., Bickhart, D. M., Kingan, S. B., Hiendleder, S., Williams, J. L., Smith, T. P. L., Phillippy, A.. 2018-02-26. Complete assembly of parental haplotypes with trio binning. https://doi.org/10.1101/271486

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