Category Archives: Genome

March 20, 2014

Image Caption: Conifers are the predominant members of the 300 million year old Gymnosperm clade. Conifers are also distinguished by their leviathan genomes. The reference genome sequence of Loblolly pine is published in the March issue of the journal GENETICS, published by the Genetics Society of America. Its 22-Gb genome size, makes it the largest genome sequenced and assembled to date. Credit: Dr. Ronald Billings, Texas A&M Forest Service

Genetics Society of America

The massive genome of the loblolly pinearound seven times bigger than the human genomeis the largest genome sequenced to date and the most complete conifer genome sequence ever published. This achievement marks the first big test of a new analysis method that can speed up genome assembly by compressing the raw sequence data 100-fold.

The draft genome is described in the March 2014 issue of GENETICS and the journal Genome Biology.

Loblolly pine is the most commercially important tree species in the United States and the source of most American paper products. The tree is also being developed as a feedstock for biofuel. The genome sequence will help scientists breed improved varieties and understand the evolution and diversity of plants.

But the enormous size of the pines genome had been an obstacle to sequencing efforts until recently. Its a huge genome. But the challenge isnt just collecting all the sequence data. The problem is assembling that sequence into order, said David Neale, a professor of plant sciences at the University of California, Davis, who led the loblolly pine genome project and is an author on the GENETICS and Genome Biology articles.

Modern genome sequencing methods make it relatively easy to read the individual letters in DNA, but only in short fragments. In the case of the loblolly, 16 billion separate fragments had to be fit back togethera computational puzzle called genome assembly.

We were able to assemble the human genome, but it was close to the limit of our ability; seven times bigger was just too much, said Steven Salzberg, professor of medicine and biostatistics at Johns Hopkins University, one of the directors of the loblolly genome assembly team, who was also an author on the papers.

The scale of the problem can be compared to shredding thousands of copies of the same book and then trying to read the story. You have this big pile of tiny pieces and now you have to reassemble the book, Salzberg said.

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Loblolly Pine Genome Largest Ever Sequenced

Bioinformatics Pioneer, Martin Reese, on Scaling Up Human Genome Interpretation
Chapters: 0:40 How did you get started in bioinformatics? 3:04 What is the biggest challenge with human genome interpretation? 8:01 Diagnosing Ogden Syndrome...

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Newswise BETHESDA, MD MARCH 20, 2014 The massive genome of the loblolly pinearound seven times bigger than the human genomeis the largest genome sequenced to date and the most complete conifer genome sequence ever published. This achievement marks the first big test of a new analysis method that can speed up genome assembly by compressing the raw sequence data 100-fold.

The draft genome is described in the March 2014 issue of the journal GENETICS and the journal Genome Biology.

Loblolly pine is the most commercially important tree species in the United States and the source of most American paper products. The tree is also being developed as a feedstock for biofuel. The genome sequence will help scientists breed improved varieties and understand the evolution and diversity of plants. But the enormous size of the pines genome had been an obstacle to sequencing efforts until recently. Its a huge genome. But the challenge isnt just collecting all the sequence data. The problem is assembling that sequence into order, said David Neale, a professor of plant sciences at the University of California, Davis, who led the loblolly pine genome project and is an author on the GENETICS and Genome Biology articles.

Modern genome sequencing methods make it relatively easy to read the individual letters in DNA, but only in short fragments. In the case of the loblolly, 16 billion separate fragments had to be fit back togethera computational puzzle called genome assembly.

We were able to assemble the human genome, but it was close to the limit of our ability; seven times bigger was just too much, said Steven Salzberg, professor of medicine and biostatistics at Johns Hopkins University, one of the directors of the loblolly genome assembly team, who was also an author on the papers.

The scale of the problem can be compared to shredding thousands of copies of the same book and then trying to read the story. You have this big pile of tiny pieces and now you have to reassemble the book, Salzberg said.

The key to the solution was using a new method to pre-process the gargantuan pile of sequence data so that it could all fit within the working memory of a single super-computer. The method, developed by researchers at the University of Maryland, compiles many overlapping fragments of sequence into much larger chunks, then throws away all the redundant information. Eliminating the redundancies leaves the computer with 100 times less sequence data to deal with.

This approach allowed the team to assemble a much more complete genome sequence than the draft assemblies of two other conifer species reported last year. The size of the pieces of consecutive sequence that we assembled are orders of magnitude larger than whats been previously published, said Neale. This will enable the loblolly to serve as a high-quality reference genome that considerably speeds along future conifer genome projects.

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Loblolly Pine Genome is Largest Ever Sequenced

Genome - Logo Ident
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In Silicon Valley, Moore's law seems to stand on equal footing with the natural laws codified by Isaac Newton. Intel co-founder Gordon Moore's iconic observation that computing power tends to double and that its price therefore halves every 2 years has held true for nearly 50 years with only minor revision. But as an exemplar of rapid change, it is the target of playful abuse from genome researchers.

In dozens of presentations over the past few years, scientists have compared the slope of Moore's law with the swiftly dropping costs of DNA sequencing. For a while they kept pace, but since about 2007, it has not even been close. The price of sequencing an average human genome has plummeted from about US$10 million to a few thousand dollars in just six years (see Falling fast). That does not just outpace Moore's law it makes the once-powerful predictor of unbridled progress look downright sedate. And just as the easy availability of personal computers changed the world, the breakneck pace of genome-technology development has revolutionized bioscience research. It is also set to cause seismic shifts in medicine.

In the eyes of many, a fair share of the credit for this success goes to a grant scheme run by the US National Human Genome Research Institute (NHGRI). Officially called the Advanced Sequencing Technology awards, it is known more widely as the $1,000 and $100,000 genome programmes. Started in 2004, the scheme has awarded grants to 97 groups of academic and industrial scientists, including some at every major sequencing company.

It has encouraged mobility and cooperation among technologists, and helped to launch dozens of competing companies, staving off the stagnation that many feared would take hold after the Human Genome Project wrapped up in 2003. The major companies in the space have really changed the way people do sequencing, and it all started with the NHGRI funding, says Gina Costa, who has worked for five influential companies and is now a vice-president at Cypher Genomics, a genome-interpretation firm in San Diego, California.

The $1,000 genome programme, now close to achieving its goal, will award its final grants this year. As technology enthusiasts look to future challenges, the coming milestone raises questions about how the roughly $230-million government programme managed to achieve such success, and whether its winning formula can be applied elsewhere. It benefited from fortuitous timing and the lack of an entrenched industry. But Jeffery Schloss, director of the division of genome sciences at the NHGRI in Bethesda, Maryland, who has run the programme from its inception, says that its achievements also suggest that there are ways to navigate publicprivate partnerships successfully. One of our challenges is to figure out what is the right role for the government; to not get in the way, but feed the pipeline of private-sector technology development, he says.

The quest to sequence the first human genome was a massive undertaking. Between 1990 and the publication of a working draft in 2001, more than 200 scientists joined forces in a $3-billion effort to read the roughly 3 billion bases of DNA that comprise our genetic material (International Human Genome Sequencing Consortium Nature 409, 860921; 2001). It was a grand but sobering success. The project's advocates had said that it would reveal 'life's instruction book', but in fact it did not make it possible to interpret how the instructions encoded in DNA were transformed into biology. Understanding how DNA actually influences health and disease would require studying examples of the links between genes and biology in thousands, perhaps millions, more people.

The dominant technology at the time was Sanger sequencing, an inherently slow, labour-intensive process that works by making copies of the DNA to be sequenced that include chemically modified and fluorescently tagged versions of the molecule's building blocks. One company, Applied Biosystems in Foster City, California, provided the vast majority of the sequencers to a limited number of customers generally, large government-funded laboratories and there was little incentive for it to reinvent its core technology.

Still, researchers had seen some advances, including robots that replaced some human work and improvements in devices capable of handling small amounts of liquid. At a 2002 meeting convened by the NHGRI, scientists predicted that such developments would drive costs down at least 100-fold over the next five years. But that was not enough.

They debated what price target would make human genome sequencing routine, the kind of thing a physician might order to help diagnose a patient on a par with a magnetic resonance imaging scan. Somebody threw out, to great rolling of eyes, 'a thousand dollars', recalls Schloss.

That seemed too ambitious, given the state of the technology. The risk associated with that is not one that your normal investor is willing to spend any money on, says Eric Eisenstadt, a retired official from the US government's Defense Advanced Research Project Agency who is now a consultant in Reston, Virginia.

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Technology: The $1,000 genome

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20-Mar-2014

Contact: C. Dana Nelson dananelson@fs.fed.us 228-832-2747 x202 USDA Forest Service Southern Research Station

U.S. Forest Service Southern Research Station (SRS) scientists co-authored the article published today in the journal Genome Biology that reports the sequencing, assembly, and annotation of the loblolly pine (Pinus taeda) genome. As the primary source of pulpwood and saw timber for the U.S. forest industry, loblolly pine is of great economic importance to the South and the nation. David Neale, professor of plant sciences at the University of California, Davis, led the loblolly pine genome project.

"The project was a huge undertaking because at 22 gigabases, the loblolly pine genome is about eight times larger than the human genome," said C. Dana Nelson, SRS Southern Institute for Forest Genetics (SIFG) project leader and research geneticist. "The group chose loblolly pine both because of its economic importance, and the knowledge gained from 60 years of breeding the species and managing millions of trees in genetic trials."

As part of the project, researchers identified a candidate for a gene involved in resistance to fusiform rust, a disease that infects southern pines. SIFG biological science technician Katherine Smith worked with John M. Davis, professor and associate director of the School of Forest Resources and Conservation at the University of Florida (UF), to compare mapped sections of the genome with sections found in loblolly specimens previously inoculated with the pathogen that causes fusiform rust.

"Fusiform rust is the most damaging disease of southern pinesand one of the most complex due to genetic interactions between the pathogen and its host," said Davis, who also serves as faculty and Executive Committee member at the UF Genetics Institute. "Genetic resistance is the only realistic way to manage the disease, which infects young trees within their first five years of growth and weakens or girdles the stem. Chemical control is expensive, impractical, and not very good for the environment."

Researchers and breeders can use the resistance genes as markers to track resistance in pine breeding populations and to guide tree planting at the stand level. "The fusiform rust pathogen has evolved to defeat some rust resistance genes in loblolly," said Nelson. "The increased molecular understanding from the loblolly genome sequencing effort provides managers with a new effective tool to determine how well seedlings will grow on a particular site."

SIFG involvement in sequencing the loblolly genome actually goes back at least two decades, when SIFG helped develop an array of resources to help speed up mapping and sequencing the loblolly pine genome and provide the ability to identify genes that influence factors such as tree growth, wood quality, stress tolerance and resistance to disease. SIFG also conserved and supplied the plant tissue used in the genome sequencing project and provided quality control on the DNA samples that were sequenced.

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In the genome of loblolly pine lies hope for better resistance to a damaging disease

Summary: The collaboration, one of many IBM is planning to widen cognitive computing's footprint, will be the first Watson implementation for genomic research.

IBM's Watson business unit and the New York Genome Center will test a cognitive computing prototype aimed at allowing oncologists to better tailor cancer care.

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The collaboration, one of many IBM is planning to widen cognitive computing's footprint, will be the first Watson implementation for genomic research.

Under the partnership:

Ultimately, IBM wants to use the Watson prototype for a clinical study by the New York Genome Center. The software and analytics tools have been under development for the past decade at IBM Research's Computational Biology Center.

The New York Genome Center specializes in experimental design, genome sequencing, bioinformatics and the computing and data storage infrastructure to crunch the data.

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IBM, New York Genome Center prep Watson prototype

There Is No Evidence For Evolution The Genome part 4 by Jason Burns
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Newswise SALT LAKE CITY The USTAR Center for Genetic Discovery is partnering with California based Omicia, Inc, to make analyzing a patients genome as routine as performing a blood test. The center, co-directed by Mark Yandell, Ph.D., and Gabor Marth, D.Sc., was launched this month with $6 million from the University of Utah and the state-funded Utah Science Technology and Research (USTAR) initiative.

Compared to 10 years ago, sequencing the human genome has plummeted in cost by 1 million-fold and can be completed in a fraction of the time. Yet there are still barriers preventing DNA sequence information from routinely being incorporated into patient care.

Current systems are not prepared for the increasing amounts of data we will be seeing within the next few years, said Marth, a computer scientist who was instrumental in the success of high profile projects such as the Human Genome Project, HapMap Project, and 1,000 Genomes Project. He relocated to the University of Utah from Boston College to apply his skills in a medical setting.

At some point all of humanity will be sequenced, and potentially more than one genome per individual, he continued. Marth and Yandell will lead efforts to tame the big data to come not only from personal genomes, but also tumor genomes and metagenomes from infectious disease agents such as viruses and bacteria.

Knowing the DNA sequence of a cancer patients tumor, for example, may reveal a personalized treatment plan for combatting the disease. Pinpointing tiny sequence variations in personal genomes will expose inherited diseases that, in some cases, may be life-threatening.

What we want to be able to do is help the kid who is born with a hard-to-diagnose genetic disorder, said Yandell. Our genome interpretation tools will be able to identify that disorder and guide treatment.

Together with Omicia, Inc., the USTAR Center for Genetic Discovery is building a web accessible informatics platform, called Opal, to distill genome data to clinically relevant findings. Opal is powered by VAAST, a proven disease gene finder algorithm invented by Yandell. Launched less than two years ago, VAAST has successfully identified causes of inherited diseases, including hard-to-diagnose rare diseases, and is used at 251 institutions worldwide.

The USTAR Center for Genetic Discovery eventually anticipates commercializing its full suite of software tools, and becoming a top genomic health data service provider for medical centers nationwide.

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From DNA to Diagnosis: USTAR Center for Genetic Discovery to Integrate Genome Data into Patient Care

Date:

March 17, 2014

Source:

NIH/National Institute of Allergy and Infectious Diseases

Summary:

Using genome sequencing, scientists have tracked the evolution of the antibiotic-resistant bacterium Klebsiella pneumoniae sequence type 258 (ST258), an important agent of hospital-acquired infections. While researchers had previously thought that ST258 K. pneumoniae strains spread from a single ancestor, the team showed that the strains arose from at least two different lineages.

Using genome sequencing, National Institutes of Health (NIH) scientists and their colleagues have tracked the evolution of the antibiotic-resistant bacterium Klebsiella pneumoniae sequence type 258 (ST258), an important agent of hospital-acquired infections. While researchers had previously thought that ST258 K. pneumoniae strains spread from a single ancestor, the NIH team showed that the strains arose from at least two different lineages. The investigators also found that the key difference between the two groups lies in the genes involved in production of the bacterium's outer coat, the primary region that interacts with the human immune system. Their results, which appear online in Proceedings of the National Academy of Sciences, promise to help guide the development of new strategies to diagnose, prevent and treat this emerging public health threat.

ST258 K. pneumoniae is the predominant cause of human infections among bacteria classified as carbapenem-resistant Enterobacteriaceae (CRE), which kill approximately 600 people annually in the United States and sicken thousands more. Most CRE infections occur in hospitals and long-term care facilities among patients who are already weakened by unrelated disease or have undergone certain medical procedures. In the new study, scientists from the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and their colleagues sequenced the complete genomes of ST258 K. pneumoniae strains collected from two patients in New Jersey hospitals. By comparing these reference genomes with gene sequences from an additional 83 clinical ST258 K. pneumoniae isolates, the scientists found that the strains divided broadly into two distinct groups, each with its own evolutionary history. Further analysis revealed that most differences between the two groups occur in a single "hotspot" of the genome containing genes that produce parts of the bacterium's outer shell. The investigators plan to further study how these genetic differences may affect the bacterium's ability to evade the human immune system.

The findings from this study highlight the wealth of information that can be gained from genome sequencing. They also demonstrate the importance of sequencing to the surveillance and accurate tracking of bacterial spread. Study collaborators included NIAID-funded scientists from Public Health Research Institute and New Jersey Medical School-Rutgers University, as well as researchers from Case Western Reserve University, the Houston Methodist Research Institute and Hospital System and NIAID's Rocky Mountain Laboratories, where the comparative genome sequencing took place.

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Scientists track evolution of a superbug