The strides scientists have made in rare disease research lately is truly impressive. For an overview of recent progress, we encourage you to check out a new article in The Pathologist from our own Luke Hickey (@Luke_Hickey), Senior Director of Strategic Marketing. It offers a great overview of how scientists have used long-read sequencing to find the genetic explanations for elusive rare diseases. “Never before have our laboratory techniques been so successful at identifying rare diseases and elucidating their underlying biological causes,” Hickey writes. “The knowledge we obtain today opens the door to new treatments, giving hope to people who…
UPDATE — November 17, 2020: This paper is now published in Scientific Data. ORIGINAL POST It’s been more than a year since we introduced HiFi sequencing to generate highly accurate long reads. In that time, we’ve seen many PacBio users make HiFi sequencing their go-to setting because it’s simple, reliable, and cost-effective. For scientists who have yet to generate their own HiFi data, we thought it might be helpful to publish a few data sets for exploration and analysis. In a new preprint, we have released HiFi data sets for five samples: mouse, frog, maize, strawberry, and a mock metagenome…
Will the next big cancer breakthrough be in immunotherapy? Therapeutic modification of the tumor microenvironment or microbiome? Or early detection and screening? Whatever the result, long-read sequencing technology can play a pivotal part in the discovery process, according to Meredith Ashby, PacBio’s director of Market Strategy for Microbial Genomics, Cancer and Immunology. In a recent article for Lab Compare, Ashby highlighted some of the ways Single Molecule, Real-Time (SMRT) Sequencing has given researchers a deeper understanding of tumors at the genomic and transcriptomic level. The benefits of applying long-read sequencing to cancer research By spanning very large structural variants in…
California redwoods: Not only are they giants in height and age (up to 379 feet high, 29 feet round, and thousands of years old), but the famous towering trees are also derived from a massive 27 Gb genome. Seeking a sequencing challenge for the Sequel II System, we picked the California redwood, or Sequoia sempervirens as it’s known to scientists. There also happened to be several fine specimens at nearby Stanford University. A small crew of PacBio scientists — Emily Hatas (@EmilyHatas), Greg Young (@PacbioGreg), and Michelle Vierra (@the_mvierra) — headed to campus to acquire samples equipped with ice, scissors,…
Herculean efforts are being made by scientists around the world to respond quickly to the COVID-19 crisis in a race to understand the virus causing the pandemic and develop diagnostics, vaccines, and therapeutics. But many research questions remain. How can long-read SMRT Sequencing technology help fill the gaps? PacBio microbiology expert Meredith Ashby highlighted several opportunities to support coronavirus research in a recent webinar as part of a day-long virtual conference hosted by LabRoots. Sequencing the viral genome Understanding the basic biology of the virus is essential, and the more detailed our investigation, the better. Highly accurate, long-read sequencing…
Image by Miroslava Chrienova from Pixabay Our team is proud to announce that PacBio has been working closely with customers to help in the fight against the COVID-19 pandemic. Scientists in commercial, academic, and government research teams are using highly accurate SMRT Sequencing data to resolve variants of the SARS-CoV-2 virus that exist within one individual or across a population of patients, which is critical to developing and maintaining effective diagnostics, vaccines, and therapeutics. Many of these efforts are powered by our HiFi reads, which are both long and highly accurate. Such reads are well-suited for applications like viral sequencing,…
UPDATE — September 1, 2020: This paper is now published in Genome Research. ORIGINAL POST — April 1, 2020 In a new preprint, scientists from the National Human Genome Research Institute, the University of Washington, and other institutions describe HiCanu, a modified version of the Canu assembler designed specifically for PacBio HiFi reads. The team put the new assembler through its paces, reporting that it significantly outperformed traditional assembly methods — even getting through centromeres, segmental duplications, and other notoriously difficult regions. As lead authors Sergey Nurk (@sergeynurk) and Brian P. Walenz, corresponding authors Sergey Koren (@sergekoren) and Adam Phillippy…
It was a pleasure to attend the annual Advances in Genome Biology & Technology meeting in sunny Marco Island, Fla., last month. The conference has a long history of supporting sequencing innovation, and during the 20th anniversary celebration this year, the tradition continued. Video and synopses from several presentations featuring SMRT Sequencing are below. Adam Ameur (@_adameur) from Uppsala University spoke about the use of long-read PacBio sequencing to detect off-target edits from CRISPR/Cas9. In a method known as SMRT-OTS, Ameur’s team used a clever adaptation of the standard PacBio library preparation to enrich for molecules bound by a guide…
Since the first PacBio instrument was released in 2011, methylation detection has been one of the advantages of SMRT Sequencing. The kinetics of nucleotide incorporation change as the DNA polymerase moves across a methylated position on the DNA template strand, producing distinctive perturbation patterns (Figure 1) that can be recognized by methylation-calling software. Figure 1: The arrows indicate the methylated positions on a 199 bp circular template. Bars indicate the ratio of the average intra-pulse distance (IPD) on the methylated template to that of the control template. Each methylation type produces a unique fingerprint. With the advent of a simple…
The new and updated species in Ensembl 99 from the Vertebrate Genomes Project (VGP) Meerkats, yaks, geese, and lots of flies — oh my! A full menagerie of new and updated animal genomes has been released by the Ensembl project. The Ensembl 99 release includes a variety of vertebrates, plants, mosquitos, and flies, as well as updates of human gene annotation and variation data. Among them are 38 new species and two dog breeds (Great Dane and Basenji), as well as four updated genome assemblies. Many were created using PacBio sequencing data. Thirteen of the new assemblies have…
With high-throughput long-read sequencing, it is now affordable and routine to produce a de novo genome assembly for microbes, plants and animals. The quality of a reference genome impacts biological interpretation and downstream utility, so it is important that researchers strive to achieve quality similar to “finished” assemblies like the human reference, GRCh38. Until a time when sequence data and resulting assemblies can regularly achieve reference-quality, assemblies should be evaluated in the three key dimensions: Contiguity, Completeness, and Correctness. However, the most commonly used measures of genome quality only tackle two of the three C’s. Contiguity is often measured as…
Diagram depicting telomere shortening. Source: http://2014hs.igem.org/Team:TAS_Taipei/project/abstract Telomeres and centromeres have long vexed genomic scientists. In the early days of genome sequencing, many researchers took it for granted that assembling these highly repetitive regions was essentially impossible. That’s why a new preprint posted to bioRxiv is so exciting. Scientists from Weill Cornell Medicine and Colorado State University describe the use of PacBio long-read whole genome sequencing to analyze and assemble telomeres, characterizing the heterogeneity of these elements across three human genomes from the Genome in a Bottle collection (HG001, HG002, HG005). “Haplotype Diversity and Sequence Heterogeneity of Human Telomeres” comes from…
The rarest day on the calendar is February 29th — which makes it the perfect time to celebrate Rare Disease Day. On this day, we join millions of people around the world making time to honor the patients, caregivers, healthcare professionals and scientists who deal with rare diseases every day. Zoe Harting was diagnosed with Type 1 SMA and was not expected to live past the age of 2, but is now reaching unprecedented milestones as an energetic 7-year-old, thanks to an experimental treatment. And we didn’t have to look far to find someone affected. Bioinformation John Harting, of our…
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),…
Launched in 1996, NARMS is a U. S. public health surveillance system that tracks antimicrobial susceptibility of select foodborne enteric bacteria. We hear a lot about the growing crisis of antibiotic resistance in human health, but it turns out this is just the most visible place it appears as it moves through our complex modern environment. For example, when intensive farming is used to feed large urban populations, antibiotic resistance can first emerge on farms and gain access to human communities through the food system. One of the key groups on the front lines of monitoring antibiotic resistance from farm…