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Thursday, March 31, 2016

With Greater Contiguity, New Gorilla Genome Assembly Offers Insights into Gene Content, SVs, and More

In a Science paper published today, scientists from the University of Washington, the McDonnell Genome Institute, and other organizations present a new gorilla genome assembly generated with PacBio long-read sequencing, representing an over 150-fold improvement over previous assemblies. From lead authors David Gordon, John Huddleston, Mark Chaisson, and Christopher Hill, and senior author Evan Eichler, the paper reports that the new assembly recovers nearly all reference exons missing from the previous assembly, and provides an unprecedented look at structural variation, genetic diversity, ancestral evolution, repeat structures, and more. The project was launched to address shortcomings with the existing gorilla assembly,…

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Wednesday, March 30, 2016

New Study Uses SMRT-ChIP Method to Find Novel Methylation in Mouse Embryonic Stem Cells

In a new Nature publication, scientists from Yale and other institutions report the discovery of N6-methyladenine (N6-mA) in mouse embryonic stem cells (ESCs), contrary to the conventional wisdom that the only form of methylation in mammals is 5-methylcytosine. Through the project, the team also developed a new method for pairing chromatin immunoprecipitation (ChIP) with SMRT Sequencing. Both of these developments have significant implications for the genomics community. “DNA methylation on N6-adenine in mammalian embryonic stem cells” comes from lead author Tao Wu and senior author Andrew Xiao, both at Yale School of Medicine. The team also included collaborators from the…

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Thursday, March 3, 2016

Prevalent Methylation in Prokaryotic Genomes Suggests Regulatory Functions

A new publication from scientists at Lawrence Berkeley National Laboratory, the Joint Genome Institute, and other organizations reports a landmark study of genome-wide methylation in prokaryotes. The analyses of 230 bacteria and archaea species revealed both more methylation than expected and novel epigenetic mechanisms. “­­­The Epigenomic­­­ Landscape of Prokaryotes” from lead author Matthew Blow, senior author Richard Roberts, and collaborators was recently published in PLoS Genetics. The team used SMRT Sequencing to detect 6-methyladenosine (m6A), 4-methylcytosine (m4C), and 5-methylcytosine (5mC) across the 230 genomes. “Bisulfite sequencing has enabled genome-wide surveys of 5mC methylation, but a historic absence of tools for…

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Thursday, February 25, 2016

New Views of Microbial Communities Call for Updates to Infectious Disease Tenets

Robert Koch In a perspective recently published in Science magazine, scientists Allyson Byrd and Julie Segre from the National Human Genome Research Institute used recent advances in microbial analysis to look at Koch’s postulates through a new lens. Published by Robert Koch in 1890, these principles have become widely accepted in microbiology as the definitive means to prove that a specific pathogen is the cause of an infectious disease. As summarized by Byrd and Segre, the postulates dictate that: “First, the microorganism occurs in every case of the disease; second, it is not found in healthy organisms; and third, after…

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Tuesday, February 2, 2016

Scientists Investigate Minor Influenza Strains in Pandemic, Revealing New Clues in Flu Transmission

On the heels of her remarkable paper tracing influenza evolution in a single host last spring, New York University’s Elodie Ghedin has come out with a new publication in Nature Genetics that offers a higher-resolution view of how the flu spreads through a population. From lead author Leo Poon at the University of Hong Kong and senior author Ghedin, “Quantifying influenza virus diversity and transmission in humans” reports the results of an international collaboration to track the Hong Kong flu pandemic of 2009. The authors began with the premise that much about the genetically diverse influenza A virus is unknown,…

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Wednesday, January 6, 2016

Scientists Develop More Accurate Variant-Calling Procedure for Important Drug Metabolism Enzyme Using SMRT Sequencing

In an article entitled “Long-read single-molecule real-time (SMRT) full gene sequencing of cytochrome P450-2D6 (CYP2D6)” in Human Mutation, authors Wangiong Qiao, Yao Yang, Stuart Scott and other colleagues at the Icahn School of Medicine at Mount Sinai demonstrate a new way of analyzing the CYP2D6 gene using PacBio long reads. This gene has been shown to have a central role in drug metabolism and is believed to be directly involved in the metabolism of ~25% of all commonly used drugs. Given its importance, CYP2D6 genotype testing is now being widely used to predict how efficiently patients will metabolize drugs such…

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Monday, November 16, 2015

Scientists Use the Iso-Seq Method to Study Genes Linked to Prostate Cancer

A team of scientists from Australia, Canada, and the US published fascinating new work that may help explain gene expression patterns seen in prostate cancer. In the course of the project, they used SMRT Sequencing and found a novel fusion transcript linking two genes with high sequence identity. “Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer” was published in Molecular and Cellular Endocrinology by lead author Gregor Tevz, senior author Colleen Nelson, and a number of collaborators. In it, the scientists attempted to untangle expression signals from two relaxin genes, which…

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Wednesday, November 11, 2015

Scientists Publish High-Quality, Near-Complete Genome of Resurrection Grass Oropetium

We’re excited about a new Nature paper from the winners of our 2014 “Most Interesting Genome in the World” SMRT Grant program. “Single-molecule sequencing of the desiccation tolerant grass Oropetium thomaeum” comes from lead authors Robert VanBuren and Doug Bryant along with senior author Todd Mockler at the Donald Danforth Plant Science Center, as well as a number of collaborators at other institutions. In it, the authors report a virtually complete genome of Oropetium thomaeum, a grass with an estimated genome size of 245 Mb and the handy ability to regrow even after extreme drought once water becomes available. The…

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Thursday, October 22, 2015

Scientists Sequence Klebsiella Strain Resistant to All Known Antibiotics

A new publication reports the discovery and analysis of a nightmare bacterium that’s genetically resistant to all commercially available classes of antibiotics. The paper, “Stepwise evolution of pandrug-resistance in Klebsiella pneumonia,” came out this month in Scientific Reports from Nature. Lead authors Hosam Zowawi and Brian Forde, along with senior author David Paterson and several collaborators, studied an isolate recovered from the urine of an 87-year-old patient who was hospitalized in the United Arab Emirates last year. They used SMRT Sequencing to characterize the strain and its genetic mechanisms for drug resistance. That strain, MS6671, “was found to be non-susceptible to…

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Tuesday, October 20, 2015

Scientists Reveal Recent Autosome-to-Y Duplication Event in Drosophila

Following on the heels of characterizing 18 Mst77Y genes that were tandemly duplicated within a 96 kb region (Krsticevic FJ, et al., 2015), scientists from institutes in Brazil, Austria, and the United States recently published a study in which they also used the Drosophila melanogaster data release from PacBio to characterize a region of the Y chromosome that had never before been accessible. In a paper published in PNAS, entitled “Birth of a new gene on the Y chromosome of Drosophila melanogaster,” lead author Antonio Bernardo Carvalho, senior author Andrew Clark, and collaborators detail their find of a gene duplicated from…

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Wednesday, August 12, 2015

Using SMRT Sequencing, Scientists Uncover Unexpected Transcript Diversity in Fungi

A new PLoS One publication from scientists at the Joint Genome Institute, University of Minnesota, and other organizations demonstrates that fungal genomes may contain far more transcript diversity than previously thought. In “Widespread Polycistronic Transcripts in Fungi Revealed by Single-Molecule mRNA Sequencing,” lead author Sean Gordon, senior author Zhong Wang, and collaborators used long-read isoform sequencing to characterize four fungal species. In addition to widespread alternative splicing, they found evidence of polycistronic transcription units that could be important engineering targets for genetic manipulation of fungi. The scientists turned to SMRT® Sequencing to escape the limitations of short-read transcriptome sequencing. “The…

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Thursday, July 23, 2015

SMRT Sequencing Provides Novel View of Long-Term Viral Evolution in a Single Patient

A group of scientists from the University of Pittsburgh School of Medicine and New York University used long-read sequencing from PacBio for a remarkable new study characterizing influenza virus evolution with unprecedented precision. “Intrahost Dynamics of Antiviral Resistance in Influenza A Virus Reflect Complex Patterns of Segment Linkage, Reassortment, and Natural Selection,” published in mBio by lead author Matthew Rogers and senior author Elodie Ghedin, reports a two-year study tracking the flu virus in one person. Although normally limited to acute infection, in this case the patient, a three-year-old with severe combined immunodeficiency disease, received multiple antiviral therapies but kept…

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Tuesday, July 14, 2015

SMRT Sequencing Contributes to Detection of DNA Methylation in C. elegans

A recent paper in the journal Cell presents novel findings of DNA methylation in C. elegans, an organism previously believed not to have such epigenetic marks. Scientists used several approaches to analyze the adenine N6-methylation (6mA) found in C. elegans, including SMRT® Sequencing to directly observe base modifications across the genome. From lead authors Eric Greer and Mario Blanco with senior author Yang Shi at Harvard Medical School, “DNA Methylation on N6-Adenine in C. elegans” describes a range of technological methods deployed to assess methylation across the worm’s genome. The team queried the nematode with specific antibodies for 6mA; immunofluorescence;…

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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, June 25, 2015

SMRT Data Delivers for Next-Generation HLA Typing at Anthony Nolan Research Institute

A new publication in PLoS One from authors at Anthony Nolan’s Research Institute describes a feasibility study for HLA typing using SMRT® Sequencing. The research institute, where the world’s first bone marrow registry started in 1973, is part of the UK-based charity dedicated to improving the outcomes of bone marrow transplantation. Scientists at Anthony Nolan are leaders in HLA typing, which is an important step in matching a bone marrow or stem cell donor to a patient in need. The Anthony Nolan team adopted the PacBio® system last year, and this publication reflects its efforts to test and establish the…

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