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New NHGRI Human Pangenome Reference Initiative Will Use Highly Accurate PacBio Sequencing

Thursday, September 26, 2019

University of Washington genome science technicians Melanie Sorensen, Katherine Munson, and Alexandra Lewis at the PacBio Sequencing Services. (Photo by Amy B. Wifert.)

The National Human Genome Research Institute has awarded nearly $30 million for new sequencing and bioinformatics initiatives that aim to better represent the full range of human genetic diversity. An entirely new human reference genome — the “pangenome” — will be built from high-quality sequencing of 350 individuals from across the human population. Here at PacBio, we’re excited that highly accurate long-read WGS data from our Sequel II Systems will be an important component of this new program.

“It has grown more and more important to have a high-quality, highly usable human genome reference sequence that represents the diversity of human populations,” said Adam Felsenfeld, NHGRI program director in the Division of Genome Sciences, in a statement announcing the news.

The Human Pangenome Project will be carried out at a sequencing center and a reference center, each having extensive collaborations with scientists at many institutions. The University of California, Santa Cruz (UCSC) will form the sequencing center with teammates at the University of Washington, Washington University in St. Louis, and Rockefeller University. Their goal will be to use cutting-edge sequencing technologies, including SMRT Sequencing, to create higher-quality assemblies than have been produced in the past. A separate reference center will be created by Washington University in St. Louis, UCSC, and the European Bioinformatics Institute. Its aim will be to pull all 350 assemblies together into a useful representation for the genomics community.

“The human pangenome reference will be a key step forward for biomedical research and personalized medicine. Not only will we have 350 genomes representing human diversity, they will be vastly higher quality than previous genome sequences,” said UCSC’s David Haussler in a statement announcing these grants. “We are going to use all of the latest and best sequencing technologies and push their capabilities to get the most complete and accurate sequences possible.”

Evan Eichler, professor of genome science at the University of Washington and a Howard Hughes Medical Institute investigator, said in a statement: “We finally have the technology and methods to go after the parts of the human genome that were beyond our reach 20 years ago. It’s an exciting time for human genetics with implications for improved variant discovery associated with disease.”

For genome sequencing with PacBio technology, scientists will use the Sequel II System’s HiFi reads for highly accurate consensus sequencing of multi-kilobase inserts. In a recently posted preprint about a haploid human genome, scientists noted that HiFi mode successfully resolved segmental duplications (SDs), which are known for being difficult to assemble; in fact, authors stated that the HiFi assembly has “the highest fraction of resolved SDs for any of the published assemblies analyzed thus far.” They concluded, “Our results suggest that HiFi may currently be the most effective stand-alone technology for de novo assembly of human genomes.”

A hearty congratulations to all the scientists who will be involved in this new initiative! We look forward to working closely with these teams as they generate much-needed data for the biomedical research community.

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