Seven years after the ALS Ice Bucket Challenge soaked the world, the pace of discovery in sporadic amyotrophic lateral sclerosis has increased tremendously, with more than $115 million dollars in donations funding research that has led to the identification of several genes implicated in both familial and sporadic cases of the neurodegenerative disease. While the social campaigns have generated much needed awareness around the disease, there are other challenges – one of which can be addressed with long-read sequencing. As detailed in a new, interactive case study, PacBio SMRT Sequencing is helping researchers at the University of Washington unravel…
It’s a challenge that has haunted rare disease researchers for years: how to increase solve rates in rare and Mendelian disease. Currently, the genetic cause of more than half of rare disease cases worldwide remain unexplained. In a series of talks and posters presented at the 2021 annual meeting of The European Society of Human Genetics (#ESHG21), PacBio experts and users described how HiFi sequencing could help close the gap by providing more comprehensive, accurate and high-definition coverage of the gaps in the human genome. Here is a summary of the discussions that took place and the posters that…
With PacBio HiFi sequencing data now readily available for organisms of any size, many exciting results have been published featuring new de novo assembly methods optimized for highly accurate long reads. These methods have produced assemblies for a variety of organisms at quality levels never before thought possible — as measured by completeness, contiguity and correctness. We feel privileged to collaborate with the scientific community on the development of these tools. From Small to Tall When the USDA wanted to rapidly assemble the Asian Giant Hornet as part of its real-time invasive species response initiative, they turned to a tool…
UPDATE: This paper has now been published in HGG Advances from Cell Press In an exciting new preprint, scientists from the HudsonAlpha Institute for Biotechnology and the University of Alabama at Birmingham describe the use of PacBio highly accurate long-read sequencing to identify pathogenic variants responsible for previously undiagnosable, rare neurodevelopmental disorders. Lead author Susan Hiatt (@suzieqhiatt), senior author Gregory Cooper, and collaborators conducted genomic analyses of several family trios in an attempt to find causal genetic variants that had been missed with earlier studies. “Large fractions of [neurodevelopmental disorders] cannot be attributed to currently detectable genetic variation,” they…
The study of genomics has revolutionized our understanding of science, but the field of transcriptomics grew with the need to explore the functional impacts of genetic variation. While different tissues in an organism may share the same genomic DNA, they can differ greatly in what regions are transcribed into RNA and in their patterns of RNA processing. By reviewing the history of transcriptomics, we can see the advantages of RNA sequencing – using a full-length transcript approach – become clearer. Reaching for the Transcriptome Even before genome sequencing became commonplace, scientists were able to measure gene expression activity using hybridization…
It’s well known that finding the genetic cause of rare diseases can be complex — that’s why so many remain unsolved. But researchers are beginning to get a grasp on just how complex these conditions can be, thanks to the heightened power of PacBio. PacBio principal scientist Aaron Wenger kicked off a recent webinar with a quote from University of Washington scientist Evan Eichler, who said “there are three key aspects to genetic disease associations: comprehensive variant discovery, accurate allele-frequency determination, and an understanding of the pattern of normal variation and its effect on expression.” Wenger explained how HiFi reads…
Assembling the genomes of the tetraploid rose has been challenging, but PacBio HiFi reads are helping Dutch researchers overcome the hurdles. The genome of the rose is almost as complicated as its connotations when given as a gift on Valentine’s Day or other special occasions. Although relatively small in size, at 400-750 Mb, with seven chromosomes, the cells of roses have multiple sets of chromosomes beyond the basic set. And these can vary widely between the commercial varieties. Some are diploids, with two homologous copies of each chromosome (like humans, with one from the mother and one from the father),…
Tychele Turner, Assistant Professor, Washington University in St. Louis School of Medicine We are pleased to announce the winner of the 2019 Human Genetics SMRT Grant: Tychele Turner, an assistant professor who recently joined the Washington University in St. Louis School of Medicine. Turner’s research focuses on neurodevelopmental disorders, particularly on finding answers to unsolved cases. Her project aims to sequence members of a family affected with autism, using long reads and the high accuracy of HiFi sequencing to try to identify a causal genetic variant. We spoke with her to learn more about this winning proposal. Q: How did…
We’d like to extend a sincere thanks to everyone who attended our two-day North America User Group Meeting, held this year at our Certified Service Provider, the University of Delaware Sequencing and Genotyping Center (@UD_DNAcore). With representation from 80+ organizations and over 160 attendees, the event was a great environment for sharing best practices and networking with the SMRT Sequencing community. Also, a big thanks to our host, Bruce Kingham (@bkingham) and team, as well as our partners: Agilent, Biosoft Integrators, Circulomics, Covaris, Diagenode, Perkin Elmer, Sage Science and Shoreline Biome. If you weren’t able to attend the meeting, we’ve…
We were delighted to host an educational workshop at last month’s annual meeting of the American Society of Human Genetics (ASHG), where we had the opportunity to feature talks from two customers as well as an overview of SMRT Sequencing. If you couldn’t attend, check out the videos or read the highlights below. Emily Hatas, our director of business development, kicked things off with a look at how SMRT Sequencing has evolved over the years. Compared to the first instrument we offered, the Sequel II System represents a 100-fold improvement in read length and a 10,000-fold improvement in throughput. As…
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…
UPDATE: The article is now published in the Annals of Human Genetics. A new preprint evaluates the utility of PacBio HiFi reads for assembly of a human genome. The study is a follow-up to a recent publication in Nature Biotechnology that introduced a technique to generate sequencing reads with both long read length and high accuracy. Evan Eichler discussed the challenges of segmental duplications during a presentation at SMRT Leiden in May. Illustration by Alex Cagan of the Sanger Institute. “Improved assembly and variant detection of a haploid human genome using single-molecule, high-fidelity long reads” comes from lead authors…
To enable better understanding of biology, sequencing data must be accurate and complete. This is especially true when seeking out variants and determining their implications. Luckily, technical and software improvements for SMRT Sequencing are making it easier to efficiently generate genome assemblies with unparalleled accuracy. As presented in a webinar by PacBio Staff Scientist Sarah Kingan (@drsarahdoom) and GoogleAI Genomics Project Lead Andrew Carroll (@acarroll_ATG), HiFi reads enabled by circular consensus sequencing (CCS) on the new Sequel II System challenge the notion that sequencing technologies require a tradeoff between length and accuracy. Highly accurate long reads (HiFi reads) offer the…
Maryland Genomics leaders with the Sequel II System In this blog miniseries, we’re recapping presentations from early access users of the Sequel II System. Today, we summarize Luke Tallon’s report from Maryland Genomics, a PacBio Certified Service Provider. Like the other early access users, Maryland received 32 SMRT Cells for use in evaluating the new sequencing system. They tested them across a range of applications: continuous long-read (CLR) sequencing for humans, plants, insects, and bacteria; and HiFi mode, powered by circular consensus sequencing, for human, microbiome, and other samples. Tallon reports that each SMRT Cell 8M averaged about 92 Gb…
The PacBio team was honored to have the opportunity to give several talks at this year’s Advances in Genome Biology & Technology conference. If you weren’t able to be there, we’ve got you covered with videos and highlights. In a plenary session, Marty Badgett, senior director of product management, gave attendees a look at the latest results using the HiFi reads with the circular consensus sequencing (CCS) mode as well as a sneak peek at data from our soon-to-be-released Sequel II System. As he demonstrated, HiFi reads cover the same molecule many times, delivering high consensus accuracy (Q30 or 99.9%)…