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ASHG PacBio Workshop: Of reference genomes and precious metals

Rick Wilson, Director of the McDonnell Genome Institute at Washington University in St. Louis titled his talk “Of reference genomes and precious metals” and walked the audience through definitions and standards for the various quality levels for de novo assembled human genomes, e.g., platinum, gold, and silver. He noted that this was a good topic for this session because of the important role PacBio has played in the community’s work to create reference-grade genomes. For example, PacBio technology has enabled them to sequence additional genomes (CHM1, CHM13) to a very high quality level. Although these sequences were essential for further refining the GRCh38 reference build, the current reference genome is still not optimal for some highly polymorphic and complex regions of the genome, and does not adequately represent diverse ancestries sufficiently. Wilson outlined their definition of a ‘gold’ genome as a high-quality, highly contiguous representation of the genome with haplotype resolution of critical regions – created with PacBio reads to perform de novo assembly, a scaffold created using BioNano and/or Dovetail aligned to reference, and BACs to fill targeted regions and shore up gaps. The list of gold genomes in progress includes the Yuroban, Puerto Rican Han Chinese, CEU, and Luhya. A ‘platinum’ genome is a contiguous, haplotype-resolved representation of the entire genome, two of which currently exist for the CHM1 and CHM13 hydatidiform moles. While ‘silver’ definition standards are to be determined, this category is generally non-trio genomes produced with PacBio and BioNano mapping, and no BAC library.

 

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