Home » The Daily Scan

This Week in PNAS

In the early, online edition of the Proceedings of the National Academy of Sciences, a UK team describes gene expression shifts in blood samples from people deprived of sufficient shuteye. Array-based transcripome profiling on samples from 26 individuals involved in week-long sleep restriction experiments indicated that insufficient snoozing can lead to higher- or lower-than-usual expression of hundreds of genes in the blood, the researchers report. Those included genes implicated in circadian rhythm, metabolism, immunity, inflammation, and more, prompting the study's authors to argue that "insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation."

A Duke University- and National Institute of Environmental Health Sciences-led group exploring the developmental influences of bisphenol A saw signs that the widespread chemical can produce epigenetic changes that curb the expression of a potassium chloride co-transporter gene called Kcc2 in cell lines produced from rat, mouse, or human cortical neurons. Follow-up experiments — including chromatin immunoprecipitation analyses showing shifts in histone and methyl binding protein levels near the Kcc2 gene in BPA-exposed neuron — further hinted that BPA is linked to epigenetic changes that alter aspects of cortical neuron development and signaling in rodents and perhaps other mammals.

Finally, the Scripps Research Institute's Kim Janda and colleagues from the US and Germany report on a potential biomarker for river blindness, or onchocerciasis, a neglected tropical disease caused by the parasitic worm Onchocerca volvulus. The investigators performed metabolomic profiling on urine samples from African individuals with or without O. volvulus infections, using liquid chromatography coupled with mass spectrometry to screen compounds in these samples. The search led to an apparent O. volvulus metabolite nicknamed NATOG, which was present in infection-positive samples in the initial analyses and in follow-up experiments. "The discovery of NATOG as a biomarker for O. volvulus should prove valuable in the development of a diagnostic," researchers write, "which will assist in facilitating disease elimination."

February 26, 2013

Another Knock Against Doctors

The O Magazine is cautioning women that doctors' lack of genomics knowhow may harm their health.

Citing a 2012 study by Arup Labs, which found that healthcare providers ordered the wrong genetic test approximately one-third of the time, reporter Cheryl Platzman Weinstock writes that although "research in the field of genetics has advanced at breakneck speed ... many doctors have little to no formal training in genetics, and that ... can lead to devastating mistakes."

Weinstock highlights the example of Lupe Acosta, a mother living in a small town not far from Los Angeles, who had already gotten one mastectomy after being diagnosed with a type of breast cancer. She decided to get genetically tested for BRCA1 and BRCA2 mutations — markers associated with heightened risk of hereditary breast and ovarian cancer — and the results said she had a variant with an unknown association to breast cancer.

However, according to Weinstock's article, it appears that Acosta understood her test results to be positive after discussing it with her oncologist. The suggestion by Weinstock, although not explicitly stated, is that Lupe's doctor recommended another mastectomy based on the results.

Further testing on Myriad Genetics' BRACAnalysis Large Rearrangement Test revealed Acosta didn't have a deleterious mutation and a second doctor's opinion was that she didn't need a preventative mastectomy. Still, Acosta decided to get the surgery anyway. "I couldn't shake the feeling that I was a ticking time bomb," Acosta tells O Magazine. "I had to go ahead with the surgery if I was ever going to move on with my life."

Increasing physicians' genomics education is undoubtedly a serious need. And our sister publications at GenomeWeb have reported on a number of efforts underway in this regard. But this story also shows the public doesn't have a good grasp of concepts of genomic risk. Lupe's original test results and interactions with her physician may have confused her about her risk for breast cancer, but a second test and a second opinion from a oncologists with genetics expertise couldn't convince her to not get a second mastectomy. If anything, this story highlights the importance of educating patients about genomics as well.

February 25, 2013 / 1 comment

Plan for Open Access

The Obama administration announced a new open-access plan on Friday, calling for the public to be able to freely access the results of federally funded research. A memo from John Holdren, who heads the White House Office of Science and Technology Policy, directs federal agencies that spend more than $100 million a year on research and development to devise a plan to implement public access to such research.

The New York Times notes that this policy affects the National Science Foundation, the Department of Energy, and the Department of Agriculture; the National Institutes of Health has an open-access policy in place.

According to the memo, the agencies are to ensure that papers stemming from research they fund should be freely available to the public within a year of publication, though that timeframe is a guideline and could differ for different disciplines.

As the Chronicle of Higher Education reports, the Association of American Publishers said in a statement that the new policy "outlines a reasonable, balanced resolution of issues around public access to research funded by federal agencies."

ScienceInsider notes that a citizens' petition to the White House from May, signed by more than 65,000 people, called on the administration to implement such open-access policies. In his response to that petition, Holdren writes that "we know that scientific research supported by the Federal Government spurs scientific breakthroughs and economic advances when research results are made available to innovators. Policies that mobilize these intellectual assets for re-use through broader access can accelerate scientific breakthroughs, increase innovation, and promote economic growth."

The agencies have six months to develop their plans.

February 25, 2013 / 3 comments

First Things First

As the UK's National Health Service takes on a £100 million initiative to sequence about 100,000 people, it has a number of questions to answer and challenges to overcome, writes Caroline Wright at Genomes Unzipped. The most pressing one, she adds, "will be to implement genomic knowledge in the clinic."

Wright says that there are a number of technical considerations that contribute to how genomic knowledge can be put to use in the clinic, from determining what and how data is stored, to interpreting and analyzing variants, and to deciding the broadness or specificity of a phenotype.

But first, she adds, the point of the project has to be refined. "Is the aim to maximize diagnostic yield, research potential, equality of access, or economic benefits?" she asks. The answer to that question, she writes, will influence who is sequenced, how the data will be used, and more.

"Doubtless part of the point of this initiative is to kick-start clinical genome sequencing in the NHS, by creating the necessary informatics architecture and manpower required," she says. "It will also generate a rich dataset to enable future research and facilitate clinical interpretation. But since this is primarily a clinical initiative, current NHS patients should benefit too."

February 25, 2013

This Week in PLOS

In PLOS Biology, two University of British Columbia researchers delve into the details of evolutionary diversity, using Escherichia coli as a model system. The team prompted initially isogenic E. coli bacteria to adapt into different populations using competition experiments involving growth in distinct carbon sources over some 1,200 generations. After sequencing and assessing the genomes of bugs undergoing adaptation through three such trials, UBC's Michael Doebeli and co-author Matthew Herron, now at the University of Montana, realized that "similar but independently evolved phenotypes often shared mutations in the same gene and, in four cases, shared identical mutations at the same nucleotide position." Such parallel mutation patterns prompted the duo to propose that adaptive diversification marches along through a "predictive evolutionary process."

Researchers from France, Australia, and the US report on a random codon re-encoding strategy for designing vaccines against Chikungunya virus in PLOS Pathogens. There, the group put together six re-encoded Chikungunya genomes representing random combinations of three 1,400 base chunks of the virus's original sequence. Through genome sequencing and other analyses, the investigators tracked replicative capability and adaptive changes in randomly re-encoded genomes passaged in primate or insect cell lines over time. Because the random re-encoding method appeared capable of creating viruses with reduced replicative fitness, study authors say, the method may hold promise for producing new live-attenuated viruses that are safe and stable over time.

Low-grade gliomas tend to have distinct sets of genomic alterations compared to their high-grade counterparts, according to a PLOS One study. A Chinese research team did array-based genotyping on matched tumor-and normal samples from nine Chinese patients with low-grade glioma and nine with high-grade glioma as part of its effort to characterize chromosomal gain, loss, or copy neutral loss of heterozygosity in the central nervous system cancers. Results of the analyses indicate that "[low-grade glioma] and [high-grade glioma appear to have different molecular signatures in genomic variations," researchers say, and "provide invaluable information for the diagnosis and treatment of gliomas in patients with variable duration or diverse tumor differentiation."

February 25, 2013

From Ducks and Horses to Clone Armies

In case you were wondering (and someone was), the Broad Institute's Eric Lander would rather study the genomes of 100 duck-sized horses than that of one horse-sized duck because "with 100, you get information about the population genetics," he said. "So you can learn cool things about why some of the duck-sized horses can fly better and others can run better."

Lander answered that, and other serious and not-so-serious questions, during a two-hour "Ask Me Anything" session on Reddit yesterday.

A number of the questions posed dealt with Lander's work on the President's Council of Advisors on Science and Technology. As part of that group, Lander said that he has met with President Obama several times and that the group has written a number of reports, including ones on the flu, science education, and climate change, and now are working to put those recommendations into action. Further, Lander noted that the time between scientists receiving their PhD and getting a faculty position needs to be shorter. "Young people should get out into the scientific world early, when they have lots of fresh ideas. We should encourage grants to young scientists and should encourage them to take big risks," Lander said. "When you're taking big risks, science is amazingly fun."

One questioner, called FiachB7, though, wanted to know whether Lander had "ever advised raising a clone army to Obama?"

Lander said no. "I have never advised the President to raise a clone army," he said. "As I recall, the clone army didn't work out so well for the Empire." (That likely lead Star Wars fans in the exchange to chuckle knowingly.) Lander also pointed out that the White House recently answered a citizens' petition regarding building a Death Star (one isn't going to be built).

And what about Lander's mustache? Basehead2002 wanted to know how long Lander had been sporting that look. Lander said he's had it since high school, and he offered "an embarrassing picture of me in high school with mustache and long (albeit era-appropriate) hair" as proof.

February 22, 2013 / 5 comments

Proteomics Skullduggery

Via Retraction Watch comes a story in Lab Times of a mysterious case of proteomics data plagiarism.

In 2005, researchers from the University of Tuscia, University of Turku, and University of South Denmark published a paper in the journal Proteomics that included as one of its figures a scan of a 2D gel containing barley proteins.

Nothing unusual about that, except, it turns out, a group at the University of Munich had submitted a paper to Proteomics several years before featuring the exact same gel. Upon noticing this apparently "stolen" gel, one of the Munich researchers got in touch with Proteomics chief editor Michael Dunn to notify him.

And here the story, reported by Lab Times' Ralf Neumann, gets interesting. Proteomics twice rejected the Munich's group paper before the gel dispute came to light. When Munich researcher Bernhard Granvogl contacted the journal's editorial staff to alert them to the issue, the staff maintained that the gels were different and that no plagiarism had taken place. However, they either (in Granvogl's telling) requested the Munich group to resubmit their twice-rejected paper, or (in Dunn's telling) entertained a request from Granvogl to resubmit. In either case, the paper was published in Proteomics in 2006, and everyone went their separate ways.

And that might have been the end of it were it not for an anonymous tip emailed last year to Lab Times suggesting it look into the matter. That tip set off an investigation — which Neumann details — by the magazine and Proteomics editors that led to a lot more questions, a few possible answers, an ultimate retraction of the 2005 paper, and a must-read story for fans of scientific skullduggery.

February 22, 2013

Test the Children

Two big advisory groups have updated their stance on genetic testing and screening of children for the first time in more than a decade this week. The American College of Medical Genetics and Genomics and the American Academy of Pediatrics released a joint policy statement in the journal Pediatrics and a scientific paper backing up their recommendations in Genetics in Medicine.

The new advice hinges less on the potential harms of genetic information to the psyches of kids and their parents than the groups' earlier positions, and encourages testing that is in children's best interest.

For those looking to avoid slogging through the whole document, Scientific American has a "Cliff's Notes" version at its guest blog.

Among the specific advice the new statement puts forward is a distinction between predictive testing for diseases that affect kids while they are still kids, and testing for diseases that only affect people once they are adults.

The new guide gives the thumbs up to genetic tests for children who have no symptoms but who are at risk for childhood-onset diseases, recommending that ideally children give their consent to the testing as well.

According to Ricki Lewis, writing at Sciam, the new recommendations have also softened toward the possibility that testing for adult-onset diseases like Huntington's might be beneficial for some children, but they still tow the more traditional line — recommending that families defer genetic testing for late-onset conditions until adulthood.

The advice of the two groups also gives a sharp "no" to direct-to-consumer genetic testing of children, but says that newborn screening tests should be offered to every family.

Our sister publication GenomeWeb Daily News has more on these recommendations here.

February 22, 2013

Abe's Old Hat

US President Abraham Lincoln is known for his stovepipe hat, and some people who oversee the Abraham Lincoln Presidential Library and Museum want to make sure that the hat they have on display is the real deal through DNA testing, the Chicago Sun-Times reports.

Some members of the panel overseeing the museum say that there is a "credibility gap" surrounding the origin of the hat, which is worth an estimated $6.5 million. The museum says that Lincoln gave the hat to a farmer in Illinois following his debate with Stephen Douglas, but, as the Sun-Times reports, ones of the farmer's descendents said in an affidavit in 1958 that the farmer received the hat while in Washington, DC, during the Civil War. The museum curator, however, says that it is a "dead" issue, according to the Huffington Post.

In any event, DNA testing may not be possible, the Sun-Times adds, as the hat does not appear to contain hair or other DNA sources, Lincoln does not have any living descendants, and any samples of his blood or tissue are small and might be harmed by sampling.

February 22, 2013 / 1 comment

Sara Will Crews Finley Dies

Sara Will Crews Finley, a geneticist at the University of Alabama at Birmingham, has died, according to the school. She was 82. Finley and her husband, Wayne, founded the medical genetics program at UAB, the first in the southeast US. She joined the medical faculty in 1960 — the school was then called Medical College of Alabama — and co-directed UAB's medical genetics lab for 30 years.

"Sara Finley was a true pioneer in medicine," Bruce Korf, the chair of the UAB genetics department, says in a statement. "She and her husband, Wayne, were among the first physicians to recognize the importance of the new field of medical genetics, and they were among the first to implement new technologies for culturing cells and analyzing chromosomes. These technologies helped untold numbers of families by providing new approaches to the diagnosis and classification of birth defects and genetic disorders, as well as enabling genetic counseling for families."

February 22, 2013 / 1 comment

This Week in Science

In Science this week, a Cornell University team reports on the results of a study using a precision nuclear run-on and sequencing assay to map the genome-wide distribution of transcriptionally engaged Pol II at base-pair resolution. They found that Pol II accumulates immediately downstream of promoters, at intron-exon junctions that are efficiently used for splicing and over 3′ polyadenylation sites. "Focused analyses of promoters reveal that pausing is not fixed relative to initiation sites, nor is it specified directly by the position of a particular core promoter element or the first nucleosome," the researchers write. Meantime, core promoter elements function "beyond initiation, and when optimally positioned they act collectively to dictate the position and strength of pausing," they add.

Also in Science, a group of National Institutes of Health researchers detail a framework for making decisions about future research with highly pathogenic avian influenza H5N1 viruses. They review two reports from mid-2012 showing that the viruses could be rendered transmissible by respiratory droplets among ferrets, and discuss international talks that led to the creation of the new framework, which calls for any research proposals involving the transmission of HPAI H5N1 among mammals by respiratory droplets to undergo additional review.

Finally in Science, a group of investigators from the University of Basel and from the Institute of Molecular Systems Biology described a new role for the Ser-Thr kinase mammalian target of rapamycin, or mTOR, which controls cell growth and metabolism by stimulating glycolysis, as well as protein and lipid synthesis. They used quantitative phosphoproteomics to identify substrates or downstream effectors of the two mTOR complexes and found that mTOR controlled the phosphorylation of 335 proteins including CAD, which catalyzes the first three steps in de novo pyrimidine synthesis. Further, mTORC1 indirectly phosphorylated CAD-S1859 through S6 kinase, and CAD-S1859 phosphorylation promoted CAD oligomerization and thereby stimulated de novo synthesis of pyrimidines and progression through S phase of the cell cycle in mammalian cells. "Thus, mTORC1 also stimulates the synthesis of nucleotides to control cell proliferation."

February 22, 2013 / 1 comment

For the Cause

DNA sequencing is increasingly becoming the go-to test to uncover the causes of rare genetic disorders, writes Gina Kolata at the New York Times. While parents seeking such a test for their children have high expectations, experts note that genetic mutations are only found in about a quarter of cases, and the test leads to better treatment plans in only about 3 percent of cases and improvement in about 1 percent of cases. "We give the impression that we can do these things because we only publish our successes," William Gahl from the National Institutes of Health says. He adds that, when seeing patients, "we try to make expectations realistic."

"It seems this is a floor in terms of the results outcome for these children, as some of them may receive better or more effective treatments in the future, because the specific nature of their disease is already known," Razib Khan at the Gene Expression blog notes. "Since most medical treatments today are marginal in effect these outcomes don't surprise or depress me, and the price point is sure to come down."

Kolata also points out that having a diagnosis can also help patients and their families access special education services as well as ease the medical claims process.

February 21, 2013

Rethinking Grant Reviews

Advisers to the National Institutes of Health have suggested a change to its grant review process that could boost its success rate, ScienceInsider reports.

The advisers recommend that "instead of allowing researchers one more shot if a proposal is rejected, NIH would give them unlimited chances to resubmit, but consider all applications to be new," ScienceInsider writes. They also suggest conducting a pilot study during which investigators would be allowed "an unlimited number of resubmissions but no more than two applications over 12 months."

According to the article, the idea is one of five that came out of the December meeting of the advisory council for NIH's Center for Scientific Review. It was originally suggested in a 2008 report that recommended an overhaul of the NIH's peer review system and an end to "the practice of allowing two resubmissions for a grant."

ScienceInsider adds that research community appears to be "divided" on the plan's merits.

February 21, 2013