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Friday, October 2, 2015

Toward Platinum Genomes: PacBio Releases a New, Higher-Quality CHM1 Assembly to NCBI

As part of our effort to support the National Institutes of Health and the Genome Reference Consortium (GRC) in creating platinum genomes for the research community and improving the reference genome, in 2014 we generated 54X SMRT® Sequencing coverage of the CHM1 cell line, derived from a human haploid hydatidiform mole, using our P5-C3 chemistry, and made it publicly available through the SRA database at NCBI. The CHM1 dataset was quickly taken up by researchers eager to use long, unbiased reads to identify regions of the genome prone to structural variation and to fill in sequence gaps in the GRC-maintained…

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Friday, September 25, 2015

Marc Salit at NIST: Defining Standards for the Human Genome

In the first podcast of a new series on the applications of long-read sequencing, Mendelspod host Theral Timpson interviewed Marc Salit, leader of the Genome Scale Measurements Group at the National Institute of Standards and Technology. Their conversation focused on how and why NIST is involved in establishing baseline measurements for the human genome.Salit, along with Justin Zook and their team at NIST, are managing the Genome in a Bottle (GIAB) Consortium to develop reference materials, data, and methods needed to assess whole human genome sequencing. Their goal is to establish a physical reference genome as a standard against which…

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Thursday, September 24, 2015

At Genome in a Bottle Workshop, Progress on New Reference Materials

Genome in a Bottle consortium The National Institute of Standards and Technology held its latest Genome in a Bottle workshop last month in Gaithersburg, Md., and we were honored to attend. NIST has performed pivotal work to establish reference materials for the genomics community, starting with its RNA spike-in standards (ERCC spike-in controls) and continuing now with the GIAB consortium. These standards are essential for quality control and we’re pleased to be working with NIST to help ensure the highest accuracy in human genome sequencing.Last year, GIAB released its first reference standard, based on the well-studied NA12878 human genome (NIST RM…

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Monday, June 29, 2015

Nature Methods Paper Uses Long-Read Data for Highly Contiguous Diploid Human Genome

A new publication in Nature Methods describes a new single-molecule assembly approach that resulted in “the most contiguous clone-free human genome assembly to date,” according to lead authors Matthew Pendleton, Robert Sebra, Andy Pang, and Ajay Ummat. The paper, “Assembly and Diploid Architecture of an Individual Human Genome via Single Molecule Technologies,” comes from a large team of collaborators at the Icahn School of Medicine at Mount Sinai, Cornell, Cold Spring Harbor Laboratory, and other institutions. Their new approach leverages the best aspects of each single-molecule data type by combining long-read sequencing for de novo assembly with single-molecule genome maps…

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Thursday, March 26, 2015

In Chronic Myeloid Leukemia Study, SMRT Sequencing Detects Resistance Mutations Early, New Splice Isoforms and More

Scientists from Uppsala University report in a recent paper that using the Iso-Seq™ method with SMRT® Sequencing allowed them to detect and monitor mutations in the BCR-ABL1 fusion gene for patients with chronic myeloid leukemia (CML). Screening mutations in this region is important for determining the point at which these patients become resistant to tyrosine kinase inhibitor (TKI) therapies, and is currently performed in the clinic using Sanger sequencing, quantitative RT-PCR, and other assays. The paper, “Clonal distribution of BCR-ABL1 mutations and splice isoforms by single-molecule long-read RNA sequencing,” was published last month in BMC Cancer from lead author Lucia…

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Thursday, February 26, 2015

AGBT Highlights, Day One: Advancing Human Reference Assembly & Sequencing in the Clinic

It is great to be here in Marco Island for the AGBT meeting! The 16th annual meeting hit the ground running with a pre-meeting workshop hosted by the Genome Reference Consortium (GRC) followed by an opening session that was more clinically focused than many attendees are used to at this tech-heavy conference. From the dynamic Q&A sessions, it was clear that these were precisely the kind of talks that people have been looking for as this meeting evolves downstream along with genomic science. The GRC workshop, entitled ‘Advancing the Human Reference Assembly’ included four speakers: Valerie Schneider (NCBI), Tina Graves-Lindsay…

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Tuesday, February 24, 2015

AGBT 2015: Seeing the Genome in a New Light (Sunshine?)

Like many others, we’re looking forward to an exciting week of science and sun at the 16th annual Advances in Genome Biology and Technology (AGBT) conference! We’re hosting a lunch workshop on Friday, February 27, in the Palms Ballroom from 12:00 pm to 2:00 pm EST. We hope you can join us onsite (please reserve your seat) and even if you’re not at the conference, you can watch the live stream. Here’s the agenda: Towards Comprehensive Genomics – Past, Present and Future The Human Genome: From One to One Million J. Craig Venter, Human Longevity Inc. Is Perfect Assembly Possible?…

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Wednesday, November 12, 2014

New Transcript Study Offers Clues to Pathogenesis of Repeat Disorders Linked to FMR1

It’s been nearly two years since a team of scientists from the University of California, Davis, School of Medicine published the first-ever complete sequence of FMR1, the gene associated with a repeat expansion that causes Fragile X syndrome. That team is once again breaking new ground, this time characterizing alternative splicing and full-length transcripts of FMR1. For both studies, the scientists relied on Single Molecule, Real-Time (SMRT®) Sequencing because its uniquely long reads allowed them to span the gene and generate sequence and isoform data that would not have been possible any other way. The new paper, “Differential increases of…

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Monday, November 10, 2014

Nature Paper Offers Novel Sequence, Structural Variant Data for a More Complete Human Genome

A new paper out in Nature extends our view into the human genome and challenges current ideas about genetic variation. “Resolving the complexity of the human genome using single-molecule sequencing” comes from first author Mark Chaisson, senior author Evan Eichler, and their collaborators at the University of Washington, University of Bari Aldo Moro, and University of Pittsburgh. In the paper, the scientists describe an important effort to fill gaps and better characterize structural variation in the human genome by using Single Molecule, Real-Time (SMRT®) Sequencing data. The team sequenced a haploid human genome, using a hydatidiform mole cell line (CHM1),…

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Wednesday, October 29, 2014

‘Revolutionizing HLA Typing’: Uppsala’s Ulf Gyllensten on How Long Reads Give Access to New Areas of the Human Genome

In a recent interview with Theral Timpson — part of Mendelspod’s series on long-read sequencing — Ulf Gyllensten, a scientist at Uppsala University, spoke about using PacBio® technology for HLA typing, human genome studies, transcriptomics, and more. Based in the medical genetics and genomics department, Gyllensten focuses on two areas: using systems biology to study biological variation in human physiology and studying the epidemiology of human papilloma virus and its genetic link to cervical cancer. He also works with the National Genomics Infrastructure, a national core facility in Sweden for genotyping and DNA sequencing, where he has access to all…

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Tuesday, October 21, 2014

Data Release: Whole Human Transcriptome from Brain, Heart, and Liver

In higher eukaryotic organisms, like humans, RNA transcripts from the vast majority of genes are alternatively spliced. Alternative splicing dramatically increases the protein-coding potential of eukaryotic genomes and its regulation is often specific to a given tissue or developmental stage. Using our updated Iso-Seq™ sample preparation protocol, we have generated a dataset containing the full-length whole transcriptome from three diverse human tissues (brain, heart, and liver). The updated version of the Iso-Seq method incorporates the use of a new PCR polymerase that improves the representation of larger transcripts, enabling sequencing of cDNAs of nearly 10 kb in length. The inclusion…

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Friday, October 10, 2014

ASHG 2014: A New Look at the Human Genome with Long-Read Sequencing

Scientists around the world are getting ready for the annual meeting of the American Society of Human Genetics taking place October 18-22 at the San Diego Convention Center. We’re looking forward to a number of excellent presentations and posters, and are delighted to see that many of them will focus on applying Single Molecule, Real-Time (SMRT®) Sequencing to human studies. If you’ll be among those attending ASHG, be sure to attend our workshop, A New Look at the Human Genome – Novel Insights with Long-Read PacBio Sequencing, taking place 12:30 – 2:00 p.m. on Tuesday, October 21. Register in advance to…

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Friday, June 27, 2014

At SFAF 2014, Great Science and High-Quality Genomes

It’s been a busy start to the summer, but we’re still basking in the top-notch presentations and posters from the Sequencing, Finishing, and Analysis in the Future meeting last month. Hosted by Los Alamos National Laboratory in Santa Fe, this has become a premier event for scientists working on sequencing protocols, analysis, and assembly methods. Many speakers presented data including reads from Single Molecule, Real-Time (SMRT®) Sequencing. Jeff Rogers from Baylor College of Medicine used long PacBio® reads with the PBJelly algorithm to fill gaps in many mammalian genomes, including sheep, rat, baboon, sooty mangabey, and mouse lemur. Tina Graves-Lindsay…

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Wednesday, May 28, 2014

The Sequence Analysis Meeting: SFAF 2014

The Sequencing, Finishing, and Analysis in the Future (SFAF) meeting kicks off today in Santa Fe, New Mexico. The conference is hosted by Los Alamos National Laboratory and focuses on the analytical details that are so important as the community assesses how to get the most out of all this sequence data. This year, we will have two PacBio speakers, and there will be a number of other talks from users of our long-read sequence data. Steve Turner, our CTO, will speak on Wednesday morning about the use of Single Molecule, Real-Time (SMRT®) Sequencing for generating highly contiguous genome assemblies…

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Tuesday, May 13, 2014

A New Approach for HLA Typing: SMRT Sequencing

Two recent news announcements demonstrate the utility of our Single Molecule, Real-Time (SMRT®) Sequencing technology in the challenging realm of HLA typing.  HLA typing — or analysis of genes in the human leukocyte antigen region of the human genome — is of critical importance for research in tissue transplantation matching, autoimmune disease-association studies, drug hypersensitivity research, and other applications. But analyzing those genes, which are highly polymorphic and contain thousands of alleles that code for proteins important in recognizing foreign antigens, has proven difficult with most technologies. Use of Sanger or short-read sequencing technologies has required other methods for confirmation…

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