PacBio HiFi Sequencing Overwhelmingly Best for Human Genome Sequencing  

This month included significant and historic achievements by the human genetics' community, using PacBio HiFi reads as a cornerstone technology for sequencing and analyzing whole human genomes. Major announcements are listed below, with links to resources and primary sources. 

PacBio HiFi reads are now perceived as having the highest value for human WGS by top KOL's in the human genetics community — providing an optimal balance of long read lengths and high accuracy — to achieve the most comprehensive variant detection for re-sequencing (small + large variants), and the best contiguity and accuracy for de novo assembly (complete chromosomes, >Q60 accuracy).

 These announcements collectively demonstrate that PacBio human Whole Genome Sequencing (WGS), with HiFi reads, continues to gain broad market awareness and adoption —for both our Variant Detection and de novo Assembly applications.

  • Telomere-to-Telomere (T2T) consortium  released the first ever complete human genome (v1.0 assembly). The genome sequence is complete for each of the 23 chromosomes, from one end (telomere), through the centromere, to the other end (telomere). The sequence accuracy is remarkable too with only 1 error per 10 million bases!  Blog post here: The (near) complete sequence of a human genome.   PacBio HiFi reads served as the cornerstone technology for sequencing and assembly of the genome — "We estimate that the consensus quality of our HiFi-based assembly exceeds Q60 (less than 1 error per million bases)" — with additional polishing to achieve the Q70 final quality scores.  NOTE: Just 5 rDNA arrays gaps remain, so technically it's a near-complete human genome.  It also contains the mitochondrial genome.
  • Telomere-to-Telomere (T2T) consortium and the Human Pangenome Reference Consortium (HPRC) are co-hosting a free online conference.  Speakers will offer new insights on chromosome 8 and report on further T2T progress towards a complete human genome assembly and you can follow along on Twitter at #T2THPRC.   Highlights already include a quote from Adam Phillippy, NHGRI stating: "the all-star of this [T2T complete human genome] assembly has been PacBio HiFi".  He also posted this Tweet today: "FWIW, I'm redoing all my own CLR projects with HiFi. It's that much better."
  • Checkmate, Chromosome 8: The First End-to-End Sequence of a Human Autosome, summarizing the recent pre-print from Glennis Logsdon, University of Washington (Eichler Lab) & the T2T consortium.  This was the first completed autosome, and first pre-print discussing T2T's achievements and sequencing and assembly methods using PacBio HiFi reads.
  • Improving the Accuracy of Genomic Analysis with DeepVariant 1.0 — Blog post by Andrew Carroll, Product Lead, and Pi-Chuan Chang, Technical Lead, Google Health describing the recent DeepVariant v1.0 release. It includes a summary of how DeepVariant improves variant calling accuracy with HiFi Reads, including the statement, "We observed no change in SNP errors, suggesting that PacBio reads are strictly superior [to Illumina reads] for SNP calling."
  • In precisionFDA Challenge, PacBio HiFi Reads Outperform Both Short Reads and Noisy Long Reads — Now featuring a short recording of Aaron presenting an overview of the results as well as a link to the Google AI blog post.
  • Google DeepVariant Boosts Accuracy of Indel Calls in PacBio Long Reads — Article published today in GenomeWeb (full text listed below) discussing the new version of DeepVariant and a summary of the outcome of the precisionFDA challenge.
  • This paper describes the generation of a small variant "truth" benchmark for the 5Mb major histocompatibility (MHC) locus of HG002 based on assembly of long and linked reads.  It is the result of an NCBI pangenome hackathon at UCSC in Spring of 2019 and subsequent contributions from the Genome in a Bottle (GIAB) consortium.  It demonstrates that HiFi reads produce highly contiguous and accurate assemblies for even the most difficult regions of the genome and that de novo assembly is a useful approach for regions where an individual genome differs significantly from the reference.  The approach of partitioning HiFi reads by haplotype and then assembling separate haplotypes is now being adopted by numerous groups, including the Human Pangenome Reference Consortium.

Contact Millennium Science today to find out more about PacBio Sequencing

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