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Wednesday, March 25, 2020

Sequencing 101: The Evolution of DNA Sequencing Tools

Welcome to the Sequencing 101 blog series – where we will provide introductions to sequencing technology, genomics, and much more! If you’re not immersed in the field of DNA sequencing, it can be challenging to keep up with the rapid evolution among all the platforms and technologies on the market. Let’s start with a quick overview of how these different technologies came about — and how each is used today. The evolution of sequencing technology.   First Generation Sequencing – Starting the Era of Genomics The process of Sanger sequencing. DNA sequencing as we know it originated in the late…

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Monday, March 23, 2020

AGBT 2020 Highlights: Reference-Grade Assemblies, Iso-Seq Data, and More

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…

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Wednesday, March 18, 2020

Prokaryotic Methylation Detection on the Sequel II System

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…

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Monday, March 16, 2020

A Menagerie of New Genomes Released by International Ensembl Project

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…

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Wednesday, March 11, 2020

SMRT Grant Winners: Three Scientists Selected to Use HiFi Sequencing to Tackle Genomic Challenges

  PacBio highly accurate long reads, known as HiFi reads, offer all the benefits of long-read sequencing with accuracy comparable to short-read sequencing. To celebrate this new paradigm in sequencing technology, we hosted the 2019 HiFi for All SMRT Grant this past fall. This SMRT Grant was open to scientists worldwide and offered three winning projects each up to six SMRT Cells 8M and sequencing on the Sequel II System by our Certified Service Providers and co-sponsors. In response to our call for projects across the range of SMRT Sequencing applications, we received many truly compelling proposals, which made selecting…

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Thursday, March 5, 2020

Beyond Contiguity – Assessing the Quality of Genome Assemblies with the 3 C’s

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…

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Wednesday, March 4, 2020

Nice to See You, Telomere: Scientists Use SMRT Sequencing for Previously Intractable Regions of the Human Genome

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…

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Friday, February 28, 2020

A Rare Opportunity to Help Tackle Daughter’s Rare Disease

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…

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Friday, February 14, 2020

A Rose is a Rose: HiFi Reads Enable Sequencing of Complex Tetraploid Species

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),…

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Wednesday, February 12, 2020

NARMS Scientists Track Antibiotic Resistance in Foodborne Bacteria Using SMRT Sequencing

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…

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Monday, February 10, 2020

PacBio Sequencing Contributes to New Japanese Reference Genome

People of Japanese descent just moved a little closer toward the promise of precision medicine thanks to a population-specific reference genome based on the de novo genome assembly of three Japanese individuals. A new preprint describing the work shows that SMRT Sequencing was instrumental in the achievement. Scientists from Tohoku University, led by Jun Takayama (@jntkym), Kengo Kinoshita (@kk824), Masayuki Yamamoto, and Gen Tamiya, aimed to create an improved reference genome resource that would better represent the genetic background of a Japanese population than the current human reference genome. “Some ethnic ancestries are under-represented in the international human reference genome (e.g.,…

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Tuesday, February 4, 2020

‘Pathway for Discovery’: SMRT Grant Winner Aims to Address the Mysteries of Autism with HiFi Sequencing

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…

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Thursday, January 30, 2020

At PAG 2020, HiFi Data ‘Transformational’ for Advancing Plant and Animal Research

What better way to start the year than a gathering of thousands of stellar scientists? We were excited, once again, to attend the Plant and Animal Genome (PAG) Conference in sunny San Diego and to showcase some of the achievements of our customers at our well-attended workshop.  For those who missed it – or just want to relive the excitement – here is an overview, and recordings of the presentations.  The workshop kicked off with our CSO Jonas Korlach looking back at the evolution of SMRT Sequencing over the last decade, and concluded with an update on the latest PacBio…

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Monday, January 27, 2020

When Snakes Strike: SMRT Sequencing Reveals Hidden “Venom-ome”

The team from AgriGenome and MedGenome helped assemble the genome and transcriptome of the lethal Indian Cobra (Naja naja) using PacBio long-read sequencing Snake milking, horse blood harvesting and brewing — antivenom production is still more medieval art than modern science. But a new high-quality snake genome may finally pull it into the 21st century. As recently reported in Nature Genetics, a team of scientists led by Somasekar Seshagiri, a former staff scientist at Genentech and now president of the nonprofit SciGenom Research Foundation (@SGRF_Science) in India, assembled the genome and transcriptome of the lethal Indian Cobra (Naja naja) using…

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Thursday, January 23, 2020

Project to Rapidly Sequence Maize Pangenome Delivers Publicly Available Resource

Matt Hufford, associate professor at Iowa State University, helped produce a 26-line maize pangenome assembly collection Maize researchers have been rejoicing over a New Year’s gift delivered by a group of 33 scientists: A 26-line “pangenome” reference collection.  The multi-institutional consortium of researchers used the Sequel System and BioNano Genomics optical mapping to create the assemblies and high-confidence annotations. They released the results on January 9, and in several presentations at the Plant and Animal Genome XXVIII Conference, less than two years after the ambitious project was funded by a $2.8 million National Science Foundation grant.  The collection includes comprehensive,…

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