Daily Archives: November 18, 2014

PUBLIC RELEASE DATE:

18-Nov-2014

Contact: Steven Salzberg salzberg@jhu.edu 410-614-6112 PeerJ @ThePeerJ

As genome sequencing has gotten faster and cheaper, the pace of whole-genome sequencing has accelerated, dramatically increasing the number of genomes deposited in public archives. Although these genomes are a valuable resource, problems can arise when researchers misapply computational methods to assemble them, or accidentally introduce unnoticed contaminations during sequencing.

The first complete bacterial genome, Haemophilus influenzae, appeared in 1995, and today the public GenBank database contains over 27,000 prokaryotic and 1,600 eukaryotic genomes. The vast majority of these are draft genomes that contain gaps in their sequences, and researchers often use these draft sequences for future analyses.

Each genome sequencing project begins with a DNA source, which varies depending on the species. For animals, blood is a common source, while for smaller organisms such as insects the entire organism or a population of organisms may be required to yield enough DNA for sequencing. Throughout the process of DNA isolation and sequencing, contamination remains a possibility. Computational filters applied to the raw sequencing reads are usually effective at removing common laboratory contaminants such as E. coli, but other contaminants may be more difficult to identify.

In a new study in PeerJ , authors from Johns Hopkins University discovered contaminating bacterial and viral sequences in "draft" assemblies of animal and plant genomes that had been deposited in GenBank. These may cause particular problems for the rapidly growing field of microbiome analysis, when sequences labeled as animal in origin actually turn out to be microbial.

In an even more surprising finding, the authors discovered the presence of cow and sheep DNA in the supposedly finished genome of a pathogenic bacterium, Neisseria gonorrhoeae. Although deposited in GenBank as a finished genome, the bacterium apparently was a draft genome that was submitted as complete, with erroneous DNA inserted in five places. If taken at face value, this data would appear to be a startling case of lateral gene transfer, but the correct explanation appears to be more mundane.

These findings highlight the importance of careful screening of DNA sequence data both at the time of release and, in some cases, for many years after publication.

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Unexpected cross-species contamination in genome sequencing projects

PUBLIC RELEASE DATE:

17-Nov-2014

Contact: Michael McCarthy leilag@uw.edu 206-543-3620 University of Washington Health Sciences/UW Medicine

In what is likely to be a major step forward in the study of influenza, cystic fibrosis and other human diseases, an international research effort has a draft sequence of the ferret genome. The sequence was then used to analyze how the flu and cystic fibrosis affect respiratory tissues at the cellular level.

The National Institute of Allergy and infectious Diseases, of the National Institutes of Health, funded the project that was coordinated by Michael Katze and Xinxia Peng at the University of Washington in Seattle and Federica Di Palma and Jessica Alfoldi at the Broad Institute of MIT and Harvard.

"The sequencing of the ferret genome is a big deal," said Michael Katze, UW professor of microbiology who led the research effort. "Every time you sequence a genome, it allows you to answer a wide range of questions you couldn't before. Having the genome changes a field forever."

Ferrets have long been considered the best animal model for studying a number of human diseases, particularly influenza, because the strains that infect humans also infect ferrets. These infections spread from ferret to ferret much as they do from human to human.

In the study, scientists at Broad Institute of MIT and Harvard, led by Federica Di Palma and Jessica Alfoldi, first sequenced and annotated the genome of a domestic sable ferret, Mustela putorius furo. They then collaborated with the Katze group on the subsequent analysis. A technique called transcriptome analysis. This technique identifies all the RNA that is being produced, or transcribed, from areas of the genome that are being activated at a given point in time. This makes it possible to see how the ferret cells are responding when challenged by influenza and in cystic fibrosis.

"By creating a high quality genome and transcriptome resource for the ferret, we have demonstrated how studies in non-conventional model organisms can facilitate essential bioscience research underpinning health," said Federica Di Palma, director of science in Vertebrate & Health Genomics at TGAC, The Genome Analysis Centre.

In the influenza portion of the study, Yoshihiro Kawaoka's group at the University of Wisconsin-Madison exposed ferrets to a reconstructed version of the virus that caused the deadly pandemic flu of 1918, the so-called Spanish flu, which killed 25 million people worldwide, and the swine-flu virus that caused the worldwide pandemic of 2009-2010 and continues to cause disease today.

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Ferret genome sequenced, holds clues to respiratory diseases

PUBLIC RELEASE DATE:

17-Nov-2014

Contact: Adrienne Vienneau avienneau@cheo.on.ca 613-737-7600 x4144 Children's Hospital of Eastern Ontario Research Institute

OTTAWA and VANCOUVER, November 17, 2014--What do a mouse, a fly, a zebrafish, a worm and yeast have in common? Together these five organisms hold the keys for scientists to better understand the basic molecular function of genes and specific gene mutations. The Canadian Institutes of Health Research (CIHR), in partnership with Genome Canada, has awarded the Canadian Rare Diseases Models and Mechanisms (RDMM) Network -- a first of its kind collaboration -- $2.3 million to investigate these molecular mechanisms and advance rare disease research.

Rare diseases are usually not the focus of research laboratories, which greatly limits our ability to discover effective therapies. We can gain insight into most rare human diseases by analyzing the equivalent genes and pathways in experimental organisms, because nature uses the same building blocks to construct organisms such as yeast, worms, flies, fish, mice and humans. This approach will underpin the RDMM Network, which is led by Drs. Phil Hieter, Kym Boycott and Janet Rossant.

"Our efforts will build on Canada's proven leadership in rare disease gene discovery through national engagement," said Hieter, senior scientist at the University of British Columbia. "We will mobilize the entire Canadian biomedical community of clinicians and model organism researchers to communicate and connect, integrate and share their resources and expertise, and work together to provide functional insights into newly discovered rare disease genes."

The RDMM Network includes all basic science researchers studying gene function in model systems and clinician scientists discovering novel disease genes in Canada. It will study biological mechanisms underlying rare diseases at the levels of genes, pathways and networks by analyzing the equivalent (orthologous) genes in the five model organisms.

"The key to success will be increased collaboration between clinicians and scientists as early as possible following the discovery of new gene mutations that cause disease," said Boycott, senior scientist at the Children's Hospital of Eastern Ontario (CHEO) and associate professor in the University of Ottawa Faculty of Medicine. "Our goal is to better understand new aspects of human biology and disease and identify therapeutic pathways that might lead to the development of new treatments for rare disease patients."

The RDMM Network, through its scientific advisory committee, will fund at least 24 catalyst projects annually. Its goals are to validate genetic variants that cause disease, advance understanding of disease mechanisms, create the rationale for treatment (e.g., identification of candidate drug targets) and establish longer-term collaborations between scientists and clinicians that will lead to subsequent funding of outstanding laboratory and/or applied research.

"Together, with our partners at Genome Canada, the Canadian Institutes of Health Research is proud to support the RDMM network, to advance efforts in rare disease research," said Dr. Paul Lasko, scientific director of the CIHR Institute of Genetics. "Their work will guide the development and improvement of treatments and therapeutics for the more than 350 million people worldwide who suffer from a rare disease."

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From mice to yeast: New network to use model organisms to study rare disease