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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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Monday, January 13, 2020

Direct Phased Genome Assembly Using Nighthawk on HiFi Reads

By Zev Kronenberg, Senior Engineer of Bioinformatics at PacBio   Since the introduction of HiFi reads the community has embraced these long and highly accurate reads for human genome assembly and paralog resolution [1-5]. At PacBio, the assembly team (Figure 1) is working to build on the accuracy of HiFi data for direct phasing during assembly. Figure 1. The PacBio assembly team. From left to right, James Drake, Zev Kronenberg (@ZevKronenberg), Derek Barnett (@DerekWBarnett), Chris Dunn, and Ivan Sović (@IvanSovic) In diploid organisms, phasing an assembly means separating the maternally and paternally inherited copies of each chromosome, known as haplotypes.…

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Wednesday, January 8, 2020

SMRT Grant Winner: Hunting for Answers in Spinocerebellar Ataxia

Cleo van Diemen, University Medical Center Groningen A hearty congratulations to Cleo van Diemen at the University Medical Center Groningen for winning the 2019 Neuroscience SMRT Grant! Van Diemen’s impressive proposal involves using PacBio long-read sequencing to find new genetic mechanisms associated with spinocerebellar ataxia (SCA). While some 70% of SCA patients can get clear diagnostic and prognostic information because they have one of the ~37 genes known to be associated with this condition, 30% of patients have no such clarity. In this project, van Diemen and her colleagues will use their SMRT Grant award to generate highly accurate long…

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Friday, January 3, 2020

Novel Workflow Produces Fully Phased Human Genome Assemblies Without Trio Sequencing

A new preprint from lead authors David Porubsky and Peter Ebert, senior authors Evan Eichler and Tobias Marschall (@tobiasmarschal), and collaborators reports a method for generating fully phased, de novo human genome assemblies without parental data. The approach combines PacBio HiFi reads (>99% accuracy, 10-20 kb) with the short-read, single-cell Strand-seq technique.  The authors provide a proof-of-principle through assembling the genome of a Puerto Rican female from the 1000 Genomes Project. The work extends a recent publication from many of the same authors in which HiFi reads were used to produce an accurate and contiguous assembly of the human haploid…

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Monday, December 23, 2019

Iso-Seq Analysis Sheds Light on Splicing Associated with Schizophrenia

Neurexin genes, which have been associated with certain neuropsychiatric disorders, are known to make heavy use of alternative splicing. In a recent study, scientists used the Iso-Seq method with SMRT Sequencing to better understand splice variants in neurons derived from human induced pluripotent stem cells (hiPSCs). The study, “Neuronal impact of patient-specific aberrant NRXN1α splicing,” was published in Nature Genetics. Lead authors Erin Flaherty (@erinkflaherty) and Shijia Zhu, senior author Kristen Brennand (@kristenbrennand), and collaborators at the Icahn School of Medicine at Mount Sinai and other institutions undertook the project to help shed light on disorders linked to exonic deletions in the…

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Thursday, December 19, 2019

Release of Six New Reference-Quality Genomes Reveals Superpowers of Bats

Photo of a pale spear-nosed bat (Phyllostomus discolor) courtesy of the Rossiter Lab (@rossiterlab) Bat lovers and animal researchers have been waiting for insights into the evolution and remarkable genetic adaptations of our winged mammalian friends, ever since the global Bat1K initiative announced its quest to decode the genomes of all 1,300 species of bats using SMRT Sequencing and other technologies. Now, the first six reference-quality genomes have been released on the Hiller Lab Genome Browser, and described in a pre-print by Sonja Vernes (@Sonja_Vernes), Michael Hiller (@hillermich) and Gene Myers (@TheGeneMyers) of the Max Planck Institute, Emma Teeling (@EmmaTeeling1) of…

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