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This Week in Genome Research

An international team led by investigators with the Wellcome Trust Sanger Institute's pathogen genomics group describes a strategy for sequencing the genomes of Chlamydia trachomatis isolates nabbed from clinical swabs without a separate bacterial culturing step. As they report in the early, online edition of Genome Research, the researchers relied on multiple displacement amplification, or MDA, to up the levels of DNA in clinical samples after enriching for the sexually transmitted bugs using a so-called immunomagnetic separation method. Combining the amplification and enrichment techniques helped to sequence the genomes of a significant subset of C. trachomatis specimens found in clinical and archived samples, the team reports, providing "new avenues of investigation for genomic research into difficult-to-culture and fastidious bacteria."

Meanwhile, researchers from the J. Craig Venter Institute and elsewhere explain how they used single-cell sequencing to characterize the genomes of Porphyromonas gingivalis pathogens from the sink drain of a hospital bathroom. That team came up with an automated approach for performing MDA on hundreds of individual bacterial cells in parallel, producing amplified DNA that was then tested by 16S ribosomal RNA sequencing to characterize the microbes present. From there, investigators narrowed in on sequence data for the periodontal disease culprit P. gingivalis, using single-cell sequence assembly software to put an almost complete P. gingivalis genome — a sequence that researchers subsequently compared with existing P. gingivalis genomes.

EMBL's Peer Bork and colleagues used metagenomic sequencing to look at ways in which antibiotic use in food and medicine influences the resistance genes found in microbial communities in the human gut. Using metagenomic sequence data on more than 250 fecal samples from 207 individuals in three countries, the team searched for sequences implicated in resistance to dozens of antibiotic types. Results of the "resistome" analysis indicated that resistance gene representation tends to coincide with the suite of antibiotics that have been long present and/or currently used in agricultural animals in each area.

April 17, 2013

The Amazon, Baseball Bats, Chocolate Chip Cookies, and Gene Patents

US Supreme Court Justices heard arguments yesterday regarding whether isolated genes may be patented, and NPR's Nina Totenberg writes that they "seemed skeptical." Turna Ray at Daily Scan sister publication GenomeWeb Daily News notes that "some justices didn't readily buy" the argument from Myriad's lawyer Gregory Castanias that isolated gene sequences are substantially different from native DNA.

"I find it very, very difficult to conceive how you can patent a sequential numbering system by nature, in the same way that I have a problem in thinking that someone could get a patent on the computer binary code merely because they throw a certain number of things on a piece of paper in a certain order," Justice Sonia Sotomayor said. "I always thought that to have a patent you had to take something and add to what nature does."

The justices turned to a number of analogies to discuss the case. Justice Samuel Alito brought up a scenario in which a plant in the Amazon was found to have medicinal value, saying that extraction and concentration of its compounds should be patentable, the Wall Street Journal reports. Sotomayor, by contrast, likened the situation to a chocolate chip cookie — the cookie itself might be able to be patented but the natural ingredients making it up like flour and sugar could not, according to NPR. Castanias, according to the Wall Street Journal, called that analogy "really simplistic."

He, instead, turned to the idea of a baseball bat. "A baseball bat doesn't exist until it's isolated from a tree," he said. "But that's still the product of human invention to decide where to begin the bat and where to end the bat."

However, Chief Justice John Roberts disagreed with that analogy, and called Myriad's approach to isolating DNA sequencing "snipping," the Journal adds. ""The baseball bat is quite different; you don't look at a tree and say, 'Well, I've cut the branch here and cut it here, and all of a sudden I've got a baseball bat.' You have to invent it," he said, according to NPR.

Additionally, the justices questioned how a ruling in this case would affect incentives to perform genetic research. "On the one hand, we do want people to invent; on the other hand, we're very worried about them tying up ... a thing that itself could be used for further advance," Justice Stephen Breyer said, according to NPR. He added that a new process to extract sap from the medicinal Amazonian plant could be patented but "what you can't patent is the sap itself."

April 16, 2013 / 3 comments

The PR Budget

Members of two US House of Representative committees — House Energy and Commerce Committee and the House Appropriations subcommittee — are asking for details on how much the National Institutes of Health spends on public relations and communications, ScienceInsider reports. Those representatives include Fred Upton (R-Mich.), Marsha Blackburn (R-Tenn.), Joe Barton (R-Texas), Joe Pitts (R-Penn.), Michael Burgess (R-Texas), Jack Kingston (R-Ga.), and Rodney Alexander (R-La.).

In a letter, the representatives ask NIH Director Francis Collins about expenditures by the National Cancer Institute. They cite an editorial that appeared in Nature last month that expressed concern regarding the $381.2 million NCI spent between 2006 and 2012 on its communication and education office.

"The news comes at an already troubling time for US cancer research," the editorial adds, alluding to cuts made necessary due to budgetary sequestration.

The lawmakers indicate, ScienceInsider adds, that such funds could go toward a number of research projects. "With increasingly tight federal budgets, every dollar invested at NIH becomes even more precious," they write.

In the letter, the representatives ask Collins to provide details as to the public relations contracts, budgets, and expenditures for all NIH institutes and centers as well as ideas on how to contain those costs. ScienceInsider notes that NCI Director Harold Varmus has been looking into the PR operations there and that an advisory group is to report on the institute's communications activities in June.

April 16, 2013

Among All the Bugs

Metagenomic sequencing may soon be a tool to identify which bacterium is making a patient sick, says news@JAMA. A recent study published in the Journal of the American Medical Association used such a culture-free approach to identify the Shiga toxin-producing Escherichia coli behind an outbreak in Germany in 2011. With this approach, they were able to identify the outbreak strain in 27 of the 40 patients with laboratory-confirmed STEC. The study was included in JAMA's special issue on genomic medicine.

The last author on that study, University of Warwick's Mark Pallen tells news@JAMA that a metagenomic approach would lessen the need for culturing. "The promise of metagenomics is that you can one day replace those work flows with a one-size-fits-all work flow," he says. "The complexity with metagenomics comes with analyzing the data. We are not there yet, but our results represent a proof of principle."

He also adds that the samples from which he and his team didn't get any results had very low bacterial loads. "I'm not too upset about the fact that we didn't get in hard cases. In each of those samples, we know the outbreak sequences are there, but we didn't go deep enough with the sequencing to find them," he says.

The researchers also were able to identify other bacterial strains such as Clostridium difficile in the samples, though they could not conclude if they were also contributing to illness.

April 16, 2013

This Week in PNAS

Eric Kandel and colleagues from Columbia University and elsewhere outline a method for cataloging sets of RNA transcripts shuttled to the synapse during learning. The enrichment-based approach takes advantage of interactions between these mRNAs and the transport protein kinesin, study authors say. For instance, in experiments on Aplysia sea slugs — a model organism for neuron research owing to its large brain cell size — the researchers unearthed almost 5,700 coding and non-coding sequences in the so-called synaptic transcriptome. "[W]e have succeeded in obtaining a comprehensive collection of RNAs targeted to Aplysia [central nervous system] synapses," they write. "We further show that myosin heavy chain mRNA, a cargo of kinesin, is localized to sensory neuron processes and is required specifically for the induction of long-term facilitation at sensory and motor neuron synapses."

Ohio State University's Carlo Croce and Stefano Volinia, from the University of Ferrara, look at the RNA and methylation profiles coinciding with survival patterns in individuals with a form of breast cancer called invasive ductal carcinoma. The duo brought together microRNA, messenger RNA, and DNA methylation data on hundreds of invasive ductal carcinoma patients assessed through the Cancer Genome Atlas — a search that uncovered 30 mRNAs and seven miRNAs showing promise as a prognostic signature, particularly for individuals with early stage tumors. The investigators subsequently verified the signature's ties to survival using data on almost 2,400 individuals with breast cancer from eight patient cohorts.

Biological interactions can offer important information for interpreting genome-wide screens, Columbia University researchers say in another study in the early, online edition of the Proceedings of the National Academy of Sciences. The team came up with a computational scheme called "cutoff linked to interaction knowledge," or CLIK, to take such interactions into account. In addition to describing the rationale for this approach, the investigators used data from five yeast gene disruption screens to highlight the potential benefits of the CLIK software and biological information it can provide.

April 16, 2013

The Buyer Is…

Thermo Fisher Scientific has agreed to buy Life Technologies for $13.6 billion, reports Bloomberg News. Thermo Fisher will be paying $76 a share for the company, adds Daily Scan sister publication GenomeWeb Daily News. GWDN notes that Canada's Financial Post had suggested in January that Life Tech was seeking a buyer and, shortly after that, the company confirmed it was undergoing a strategic review.

The Wall Street Journal notes that Thermo Fisher had to "[fend] off competition at the end of an auction process from a private-equity group and another industry bidder, Sigma-Aldrich." Ross Muken, an analyst at International Strategy & Investment Group, tells Bloomberg that the price was higher than what analysts had expected. The Life Tech purchase gives Thermo "reach across all the major technologies," he says, adding, "You now have a unique customer touch and a portfolio others will be unable to match."

The deal is expected to close toward the beginning of 2014, GWDN adds.

April 15, 2013

In the Last 10 Years

The Human Genome Project was completed 10 years ago yesterday, and in the intervening time, there have been a number of advances in genome sequencing and biology, the National Human Genome Research Institute says. According to its calculations, the cost to generate a human genome sequence has dropped from about $1 billion when the project began in 1990 to between $10 million and $50 million when the project ended to between $3,000 and $5,000 today. Also, in the past 10 years the number of human genomes that have been sequenced has skyrocketed from just one to thousands, and there are now nearly 3,000 genes with known phenotypes or disease-causing mutations.

"On the 10-year anniversary of the completion of the Human Genome Project, it is appropriate to celebrate our accomplishments over the past decide and to reflect on the impact of genomics on research, medicine, and society," Eric Green, the NHGRI director, says in a statement. "By improving our understanding of basic genome biology, the genomic underpinnings of disease and genomic medicine, the field gets ever closer to its ultimate goal — improving human health through genomics research."

The NHGRI numbers also note that the number of drugs with pharmacogenetic information on their labels has jumped from four in 1990 to more than 100 in 2013.

April 15, 2013

The Right Question?

The US Supreme Court today is hearing arguments in the Association for Molecular Pathology et al. vs. Myriad Genetics gene patenting case, bringing up the question of whether genes, particularly isolated genes, may be patented. The question the court has to consider, New York University law professor Rochelle Dreyfuss tells NPR is: "Is the thing that's isolated significantly different from the way that it was when it was in nature?" Products of nature cannot be patented.

The New York Times asks, though, whether that question is outdated. "Another question could trump it: Has the field of genetics moved so far so fast that whatever the court decides, it has come too late to the issue?" writes Andrew Pollack at the Times. He adds that whole-genome sequencing may not infringe on single, isolated gene patents and that cancer centers with such technologies are sequencing cancer genes to help determine the best treatments for patients.

"Events on the ground have overtaken the law," James Evans, a professor at the University of North Carolina at Chapel Hill tells the Times. He adds that decision "will be much more ideological than it will be practical."

April 15, 2013 / 3 comments

AMDeC Saying Good-bye

AMDeC said late on Friday that it is shutting down.

The board has decided to close the doors on the Academy for Medical Development and Collaboration, or AMDeC, after 15 years, it said, though it did not say why. The organization was in created in 1997 to "facilitate and encourage collaboration among the major research institutions in the [New York] region.

"We are proud to say that we have achieved this — and much more," it said in a statement.

AMDeC President and CEO Maria Mitchell told Daily Scan sister publication GenomeWeb Daily News less than seven months ago that it was expanding its mission and developing new initiatives to help its members save on costs to better ride through the economic downturn.

April 15, 2013

This Week in PLOS

Two microbial species are especially common in the core community of microbes inside the human bed bug, Cimex lectularius, according to a PLOS One study. The University of Cincinnati's Regina Baucom and company used 16S ribosomal RNA sequencing to characterize collections of intra-bed bug microbes, using 31 bed bug samples collected at eight urban sites across Ohio. The analysis turned up a range of microbial species, researchers say. But the core microbiome in the blood-sucking pests was made up of mainly two microbes: the obligate endosymbiont Wolbachia and an unnamed gamma-proteobacterium that resembles an endosymbiotic species previously found in the leafhopper.

An international team led by investigators in Germany explores the relationship between genetic variation on the Y chromosome, geography, and language groups in native South Americans. As they reported in PLOS Genetics, the researchers looked at SNP and short tandem repeat patterns on the Y chromosomes of 1,011 men from 50 tribal populations in 81 South American locales. Though they did not see genetic variant profiles with clear ties to tribal geography or language groups on the continent, investigators did find a new Y chromosome haplotype that seems to have been introduced to the area within the past 6,000 years.

In PLOS Neglected Tropical Diseases, researchers from Italy and Slovakia report on a phylogeographical analysis of the parasitic roundworms Ascaris lumbricoides and A. suum species. Using a PCR-restriction fragment length polymorphism method, the team assessed nuclear gene profiles in 143 Ascaris worms from pigs and another eight from human hosts. Together with mitochondrial gene sequence data on the same samples, the PCR-RFLP profiles allowed the team to assess phylogeny and phylogeography of the worms, which came from Italy, Slovakia, Hungary, Syria, Romania, and Pakistan. "Results obtained suggest that A. suum and A. lumbricoides may be variants of the same species," study authors say, "with the lack of fixed genetic differences and considerable phylogeographic admixture confirming an extremely close evolutionary relationship among these nematodes."

April 15, 2013

Steak, Bacteria, and Heart Disease

A link between eating red meat and heart disease has been known for a while, but just how eating a steak leads to atherosclerosis isn't quite clear, writes The Economist. Stanley Hazen from the Cleveland Clinic, though, says the effect might be mediated through the gut microbiome.

As they report in Nature Medicine, Hazen and his team found that intestinal microbes metabolize L-carnitine, a trimethylamine found in red meat, to trimethylamine-N-oxide, which, in mice, leads to atherosclerosis. Trimethylamine-N-oxide levels, they added, were higher in human omnivores than in human vegetarians or vegans.

The necessary microbes, The Economist notes, are not always present — vegetarians and vegans are less likely to be able to produce trimethylamine-N-oxide, even after taking carnitine supplements or when persuaded "in the interests of science" to eat a steak. And when antibiotics are used to kill off gut bacteria, even steak eaters produce less trimethylamine-N-oxide.

In a cohort of nearly 2,600 people, plasma levels of it and its L-carnitine precursor were associated with increased risk for cardiovascular disease and cardiac events like heart attack or stroke. And in mouse studies, the researchers found that prolonged exposure to L-carnitine led mice to develop atherosclerosis.

While "the precise chain of events linking microbes to heart disease is still unclear," The Economist adds that "this study suggests that people looking for the link between heart disease and the eating of meat have been ignoring two culprits, carnitine and bacteria."

April 12, 2013

Mass Spec on the March

Mass spec is taking over the world, pharma researcher Derek Lowe writes this week on his blog In The Pipeline.

Or, at least, it's taking over his world, which is to say, the world of biopharma research.

The technology might still be struggling for acceptance in realms like clinical proteomics, but in biopharma "there are just so many things that you can do with modern instrumentation that the assays and techniques just keep on coming," Lowe writes, singling out a recent paper in Angewandte Chemie in which researchers used MALDI mass spec to detect deacetylation on a histone peptide.

The assay offers an alternative to fluorescence-based assays that, Lowe notes, have "(notoriously) been shown to cause artifacts."

And this example isn't a one-off, he adds. A number of such mass spec-based assays have been published in journals, with even more unpublished examples "worked out inside various biopharma companies for their own uses."

April 12, 2013

Supreme Showdown

The US Supreme Court is gearing up to hear arguments in the Myriad Genetics gene patenting case on Monday. The Myriad patents cover the isolated BRCA1 and BRCA2 genes, which increase the risk of breast, ovarian, and other cancers, while critics say isolated DNA is a product of nature and, therefore, is not patentable. The implications of a decision in The Association for Molecular Pathology v. the US Patent and Trademark Office and Myriad Genetics case, Heidi Ledford at Nature writes, may not be as broad as some think.

"Symbolically, this case is a pretty big deal," Duke University's Robert Cook-Deegan tells Nature's Ledford. "But the practical consequences of it are limited."

University of Medicine and Dentistry of New Jersey's Jeffrey Rosenfeld and Christopher Mason from Cornell University recently wrote in Genomic Medicine that, according to their analysis, about 41 percent of the human genome could be covered by patent claims. Ledford at Nature notes that other researchers like Christopher Holman, a law professor at the University of Missouri-Kansas City, and Harvard Law School's Nicholson Price place that percentage closer to a quarter.

The case, Ledford adds, focuses on isolated gene patents, and there are other types of patents that also cover genes. And Harvard's Price says that whole genome sequencing likely would not infringe any gene patents as it looks at the full scope of the genome rather than at isolated DNA. Cook-Deegan adds, though, that if the court does take a broad view of the case, whole-genome approaches could be affected.

A decision in the case is expected toward the end of June, Nature adds.

April 12, 2013 / 2 comments