Quality Statement

Pacific Biosciences is committed to providing high-quality products that meet customer expectations and comply with regulations. We will achieve these goals by adhering to and maintaining an effective quality-management system designed to ensure product quality, performance, and safety.


Image Use Agreement

By downloading, copying, or making any use of the images located on this website (“Site”) you acknowledge that you have read and understand, and agree to, the terms of this Image Usage Agreement, as well as the terms provided on the Legal Notices webpage, which together govern your use of the images as provided below. If you do not agree to such terms, do not download, copy or use the images in any way, unless you have written permission signed by an authorized Pacific Biosciences representative.

Subject to the terms of this Agreement and the terms provided on the Legal Notices webpage (to the extent they do not conflict with the terms of this Agreement), you may use the images on the Site solely for (a) editorial use by press and/or industry analysts, (b) in connection with a normal, peer-reviewed, scientific publication, book or presentation, or the like. You may not alter or modify any image, in whole or in part, for any reason. You may not use any image in a manner that misrepresents the associated Pacific Biosciences product, service or technology or any associated characteristics, data, or properties thereof. You also may not use any image in a manner that denotes some representation or warranty (express, implied or statutory) from Pacific Biosciences of the product, service or technology. The rights granted by this Agreement are personal to you and are not transferable by you to another party.

You, and not Pacific Biosciences, are responsible for your use of the images. You acknowledge and agree that any misuse of the images or breach of this Agreement will cause Pacific Biosciences irreparable harm. Pacific Biosciences is either an owner or licensee of the image, and not an agent for the owner. You agree to give Pacific Biosciences a credit line as follows: "Courtesy of Pacific Biosciences of California, Inc., Menlo Park, CA, USA" and also include any other credits or acknowledgments noted by Pacific Biosciences. You must include any copyright notice originally included with the images on all copies.


You agree that Pacific Biosciences may terminate your access to and use of the images located on the PacificBiosciences.com website at any time and without prior notice, if it considers you to have violated any of the terms of this Image Use Agreement. You agree to indemnify, defend and hold harmless Pacific Biosciences, its officers, directors, employees, agents, licensors, suppliers and any third party information providers to the Site from and against all losses, expenses, damages and costs, including reasonable attorneys' fees, resulting from any violation by you of the terms of this Image Use Agreement or Pacific Biosciences' termination of your access to or use of the Site. Termination will not affect Pacific Biosciences' rights or your obligations which accrued before the termination.

I have read and understand, and agree to, the Image Usage Agreement.

I disagree and would like to return to the Pacific Biosciences home page.

Pacific Biosciences

Checkmate, Chromosome 8: The First End-to-End Sequence of a Human Autosome

Monday, September 21, 2020

UPDATE: The paper is now available in Nature.

Even in the field of genomics where new breakthroughs occur every few months, completion of the first-ever fully sequenced human autosome is a momentous achievement. Highly accurate, no gaps, no mis-joins — just chromosome 8 in all its glory. It’s a remarkable feat and we are honored that PacBio HiFi reads played a pivotal role in helping to achieve it.

The complete centromere sequence of chromosome 8 shows a diversity of satellite repeats and other abundant genomic repeats, now with near perfect base-level resolution from end to end. Logsdon, G et al. (2020)

This work is described in a preprint recently posted to bioRxiv from lead author Glennis Logsdon (@glennis_logsdon), senior author Evan Eichler, and their collaborators in the Telomere-to-Telomere (T2T) Consortium. It is part of the broader T2T initiative to sequence and assemble the first truly complete human genome and follows the earlier release of the fully sequenced X chromosome.

“Since the announcement of the sequencing of the human genome 20 years ago, human chromosomes have remained unfinished due to large regions of highly identical repeats located within centromeres, segmental duplication, and the acrocentric short arms of chromosomes,” the authors note. “The advent of long-read sequencing technologies and associated algorithms have now made it possible to systematically assemble these regions from native DNA for the first time.”

Chromosome 8 made an attractive target for the T2T’s first autosome due to its manageable centromere (previously estimated at 1.5 Mb to 2.2 Mb long). But the chromosome is also home to “one of the most structurally dynamic regions in the human genome—the β-defensin gene cluster located at 8p23.1—as well as a neocentromere located at 8q21.2, which have been largely unresolved for the last 20 years,” the scientists write.   The β-defensin cluster plays a key role in innate immunity and structural variation in this region has long been implicated in human disease.

The new assembly, which addresses all five of the previously intractable gaps in the human reference genome, was built with a clever method using several data sets, including accurate long reads: “More than half of the PacBio HiFi data is contained in reads greater than 17.8 kbp, with a median accuracy exceeding 99.9%.” After a scaffolding step based on Oxford Nanopore reads, contigs assembled from PacBio HiFi reads were swapped in to provide the base-pair resolution. “We improved the base-pair accuracy of the sequence scaffolds by replacing the raw ONT sequence with several concordant PacBio HiFi contigs,” the team reports.

The complete chr8 sequence clocks in at 146 Mb and includes more than 3 Mb missing from GRCh38. As Logsdon et al. write, “The result is a whole-chromosome assembly with an estimated base-pair accuracy exceeding 99.99%.”

The scientists also tackled that persnickety β-defensin gene cluster, “which we resolved into a single 7.06 Mbp locus—substantially larger than the 4.56 Mbp region in the current human reference genome,” they note. Nearly all of that sequence data — 99.9934% of it, to be precise — came from HiFi reads. The complete centromere, meanwhile, accounted for 2.08 Mb.

With this beautiful assembly in hand, the T2T team took it out for a spin. First, they validated it with a host of orthogonal tools, such as optical mapping. Next, they generated HiFi data for the chromosome 8 orthologs in chimpanzee, macaque, and orangutan to compare the sequence data and reconstruct the evolutionary history of the human autosome. “Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved specifically in the great ape ancestor, and the centromeric region evolved with a layered symmetry,” the team writes. “We estimate that the mutation rate of centromeric satellite DNA is accelerated at least 2.2-fold, and this acceleration extends beyond the higher-order α-satellite into the flanking sequence.”

Finally, the researchers performed an analysis of full-length transcripts produced with the Iso-Seq method.  That process identified “61 protein-coding and 33 noncoding loci that map better to this finished chromosome 8 sequence than to GRCh38, including the discovery of novel genes mapping to copy number polymorphic regions,” they report.  Twelve of these new genes were uncovered in that tricky β-defensin locus alone.

A combination of HiFi genome assembly and RNA annotation with Iso-Seq data added these 12 new genes to the β-defensin (DEFB) region of chromosome 8. Logsdon, G et al. (2020)

For so many of us in the genomics community, this paper represents far more than the sequence of a single human chromosome. It’s a statement about what science can accomplish now, and where that may lead us in the years to come. As the authors summarized: “Now that complex regions such as these can be sequenced and assembled, it will be important to extend these analyses to other centromeres, multiple individuals, and additional species to understand their full impact with respect to genetic variation and evolution.”

Learn more about the research in this on-demand Labroots presentation, and find out more about whole genome sequencing and the Iso-Seq method on our site.

Subscribe for blog updates:



Press Release

PacBio Grants Equity Incentive Award to New Employee

Friday, January 14, 2022