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Thursday, February 25, 2016

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

[caption id="attachment_11533" align="alignright" width="231"] Robert Koch[/caption] 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…

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Wednesday, September 23, 2015

SMRTest Microbe Grant Winner: Identifying Antibiotic Resistance Mechanisms with SMRT Sequencing

We’re pleased to announce the winner of our recent “SMRTest Microbe” grant competition. Congratulations to Dr. Erin Price at the Menzies School of Health Research in Australia! The grant program, co-sponsored by PacBio and the Institute for Genome Sciences (IGS), was very competitive, with more than 100 submitted proposals.Dr. Price will receive SMRT® Sequencing and analysis from IGS  — using up to 4 SMRTbell™ libraries and 8 SMRT Cells — to characterize the mechanisms behind the emergence of antibiotic resistance in Burkholderia pseudomallei, a highly pathogenic bacterium that causes the potentially deadly disease melioidosis. Dr. Price and colleagues have recently…

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Wednesday, August 26, 2015

In Bacterial Study, Scientists Link Epigenetic Switch to Virulence, Antibiotic Resistance, and More

Scientists from Griffith University, Ohio State University College of Medicine, and other institutions recently published a detailed study of phase-variable expression of a DNA methyltransferase in non-typeable Haemophilus influenzae, the predominant cause of pediatric middle ear infections. The team found that the bacterium’s epigenetic switch regulates proteins used in current vaccine candidates and influences important traits including antibiotic resistance, ability to evade the host immune system, and biofilm formation, which significantly contributes to chronic infection. The paper, “A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae,” was published in Nature Communications last month by lead…

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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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Thursday, May 28, 2015

Microbial Madness: Talks, Posters, and SMRTest Microbe Grant Program at ASM 2015

For some people, Mardi Gras and beignets are big attractions in New Orleans — but for us it’s all about the annual conference of the American Society for Microbiology. With more than 8,000 attendees, ASM 2015 will take place at the Ernest N. Morial Convention Center from May 30 to June 2 and will feature some of the leading scientists in the field. At 2:30 p.m. on Sunday, May 31, in La Nouvelle Orleans Ballroom B, Jing Li from Tsinghua University will discuss the detection and importance of three DNA methylation motifs in the genome of Streptococcus pneumonia. Shortly after,…

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Thursday, December 4, 2014

A New Reference Genome for Shigella: SMRT Sequencing of a Historic Sample

In a special issue of The Lancet dedicated to World War I, an article by scientists from the Wellcome Trust Sanger Institute used Single Molecule, Real-Time (SMRT®) Sequencing to decode the genome of the first isolate ever collected of Shigella flexneri. The bacterium, a descendant of E. coli and first identified as a separate strain in 1902, was responsible for severe dysentery among World War I troops due to poor hygienic conditions in the trenches. Today, S. flexneri is one of the leading causes of diarrheal death among children in developing countries and other areas of poor sanitation. Hoping to…

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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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Monday, October 6, 2014

‘The Quality of PacBio Data Is Beyond Compare’: Eric Schadt on Applications of SMRT Sequencing to Human Genetics

As part of its continuing series on long-read sequencing, last week Mendelspod aired an engaging interview with Eric Schadt, Professor & Chair of Genetics and Genomic Sciences, and Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai. Having now spent three years in his role at the groundbreaking institute, he reports that they are making great progress in the quest to build better data-driven health profiles around individuals that may better guide healthcare choices. On short-read versus long-read sequencing Short-read sequencing technologies still maintain the advantage in terms of throughput, says Schadt, but there are a…

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Tuesday, September 30, 2014

New Papers Detail Complexity of Methylome-Related Virulence in Human Pathogens

In two new publications, one published today, scientists from Australia, Italy, the UK, and the US report critical and surprising new findings about DNA methylation-related complexity of bacteria. Adding to the list of advances from genome-wide epigenetic analysis, these projects enhance our understanding of how methylation systems work in human pathogens — and offer important clues for future investigations into how to treat them. Today’s paper, “A random six-phase switch regulates pneumococcal virulence via global epigenetic changes,” was published in Nature Communications by scientists at the University of Leicester, University of Siena, University of Adelaide, and Griffith University. Senior authors…

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Tuesday, September 23, 2014

Science Perspective: “Tracking Antibiotic Resistance”

In the current issue of Science there is an interesting Perspective by Scott Beatson and Mark Walker of the University of Queensland discussing research published this week in Science Translational Medicine by Conlan et al. who used SMRT® Sequencing to track plasmid diversity of hospital-associated infectious bacteria at the NIH Clinical Center. The article provides a nice overview of the paper, including an explanation of the important role that plasmids play in spreading antibiotic resistance. They illustrate why short-read DNA sequencing technologies are insufficient in resolving them and long reads are necessary for this work. “Plasmids may be viewed as…

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Wednesday, September 17, 2014

NIH Study: Finished Genomes Provide Actionable Data to Combat Spread of Drug-Resistant Bacteria

A study launched over concerns around hospital-acquired infections has led to a recommendation for better microbial screening of patients upon admission. The research, from scientists at several NIH institutes, found that cases of hospital-acquired infection were less common than cases where patients were likely already colonized but received false negative results from basic screening. The study was made possible by Single Molecule, Real-Time (SMRT®) Sequencing, which allowed researchers to sequence plasmids and analyze their diversity and likely phylogeny. Short-read sequencing and strain-typing technologies could not provide the information necessary for a comprehensive analysis. “Single-molecule sequencing to track plasmid diversity of…

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Monday, August 18, 2014

Genome-Wide Methylation in Human Microbiome Samples

Scientists in Florida and Finland recently published a report of their work studying methylation patterns in two human microbiome samples. While microbiome studies have become quite popular, the authors note there have been no prior papers detailing genome-wide methylation of bacteria found in those studies. Their goal was to ascertain how much added functional variation might occur based on methylation patterns. “The methylome of the gut microbiome: disparate Dam methylation patterns in intestinal Bacteroides dorei,” published in Frontiers in Microbiology, comes from lead author Michael Leonard and senior author Eric Triplett at the University of Florida plus a team of…

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Tuesday, July 29, 2014

Novel Study of Genome-wide PT Modifications in Bacteria Performed with SMRT Sequencing

A recent paper from scientists in China and the United States demonstrates a novel view of phosphorothioate (PT) DNA modifications in two bacterial genomes. Scientists from Shanghai Jiao Tong University, Massachusetts Institute of Technology, Wuhan University, and Pacific Biosciences teamed up to deploy Single Molecule, Real-Time (SMRT®) Sequencing to generate the first genome-wide view of PT modifications and to better understand their function. “Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences” by Cao et al. was published in Nature Communications. The authors note that PT modifications, which replace a non-bridging phosphate oxygen with sulphur, were only recently…

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Monday, June 23, 2014

Unprecedented Read Length at the Icahn Institute:
Precise Sizing + SMRT Sequencing

At the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai in New York City, technology development expert Robert Sebra, Ph.D., sees tremendous need for long-read, high-accuracy sequencing for use in microbial surveillance, detection of repeat expansions, and other research applications. To meet that demand, he relies on Single Molecule, Real-Time (SMRT®) Sequencing from Pacific Biosciences with BluePippin™ automated DNA size selection from Sage Science. Together, these tools offer a powerful solution and industry-leading read lengths that allow Sebra and other researchers to resolve repeat elements and structural variants, rapidly close microbial genomes, and measure epigenetic marks. Sebra, an…

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Thursday, May 29, 2014

Research Studies Use Sequencing to Track Path of Infection Outbreaks

A talk at last week’s ASM conference continued the recent trend of scientists using Single Molecule, Real-Time (SMRT®) Sequencing in research projects designed to better understand the transmission path of hospital-acquired infections. The presentation, entitled “Tracking Hospital Patients and Environment with Complete Genome Sequencing of Carbapenem-Resistant Klebsiella pneumoniae and other Enterobacteriaceae,” came from Julie Segre, a chief investigator at the National Human Genome Research Institute. Segre spoke of Klebsiella as “the nightmare bug.” From the earliest reports of it in 2001, it is now in more than 40 states in the US and shows strong resistance to antibiotics. The study…

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