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Health Reform Covers Breast Cancer Test

Genetic testing for breast cancer is to be covered as a preventive service under the US Affordable Care Act, reports MyHealthNewsDaily. A clarification from the Department of Health and Human Services, the Department of Labor, and the Department of Treasury says that asymptomatic, high-risk women — typically with a family history of breast or ovarian cancer — will be able to get tested for the breast cancer risk genes BRCA1 and BRCA2 with no co-pay. This rule applies to non-grandfathered insurance plans.

"We view this clarification as a recognition of the critical value of BRACAnalysis as a preventive service in women's health," Pete Meldrum, the president and CEO of Myriad, says in a statement. "This designation goes a long way in ensuring that high-risk women can now have access to the life-saving preventive information provided by BRACAnalysis without the financial burden of out-of-pocket expenses."

As our sister publication Pharmacogenomics Reporter notes, Myriad is the only commercial US provider of BRCA testing and "this classification will likely broaden access to Myriad's BRCA tests."

March 08, 2013

When DTC Testing Isn't Enough

In a guest post at the Genomes Unzipped blog, two researchers from the University of California, Berkeley, discuss how genotype imputation could help consumers get more information out of their 23andMe testing results by predicting or "imputing" variants that are not assayed by the genotyping chip.

Berkeley's Peter Cheng and Eliana Hechter say that the imputation process involves comparing 23andMe data — or data from some other direct-to-consumer testing company — with a reference panel from the 1000 Genomes or HapMap projects. Since these reference datasets have a much larger pool of SNPs than DTC chips test for and because humans have a common genetic ancestry, the imputation algorithms can predict other variations that would likely be present in the user's genome if it was fully sequenced.

Basically, "the imputation algorithm models your genome as a mosaic of related genomes, and uses these related genomes to fill in all of your missing data," the post says.

There are different programs that can be used to predict genotypes. Hechter and Cheng say they used one called Impute2 which was developed by a team from the University of Oxford. They've also written a handy script that transforms 23andMe raw data files into a format that is compatible with Impute2.

Hechter and Cheng do note that 23andMe updates its genotyping chip from time to time and customers can upgrade their data for a fee.

And the results appear to be quite accurate, according to the post. "To give a rough idea, the average confidence was 97.58 percent across all SNPs [Cheng] imputed in his own genome," they write.

Also, Hechter says she was able to impute BRCA2 variants that she quite likely has, which are not included on the 23andMe chip.

March 08, 2013

Back to Work

Roger Perlmutter is to take the helm of Merck's research and development branch, the Wall Street Journal reports. Previously, Perlmutter was the executive vice president of research and development at Amgen until his retirement about a year ago and prior to joining Amgen he was worked in basic research at Merck. "By hiring Dr. Perlmutter, Merck is tapping into his experience in the field of biotechnology-style drugs, in which Amgen was a pioneer," the Journal notes. While at Amgen, Perlmutter oversaw the FDA approval of a number of drugs.

"I am honored to have the opportunity to return to Merck and to lead MRL," Perlmutter says. Perlmutter is to replace Peter Kim, who is retiring in August. The Journal adds that under Kim, Merck garnered the approval of a number of vaccines and drug, but has recently been beset by setbacks.

March 08, 2013

This Week in Science

In this week's Science, a team led by researchers from Heinrich Heine University and Oklahoma State University report on the discovery that the red alga Galdieria sulphuraria, which lives in the toxic conditions of volcanic sulfur springs, acquired some of the genes it needs to survive from simpler organisms such as bacteria. The investigators sequenced the alga's genome and found acquired at least 75 genes through horizontal gene transfer. Around 5 percent of the alga's protein-coding genes were transferred from prokaryotes in this manner, including ones involved in "ecologically important processes ranging from heavy-metal detoxification to glycerol uptake and metabolism," the researchers write.

Also in Science, scientists from GlaxoSmithKline and Stanford University urge the inclusion of patients' clinical, social, and environmental histories along with genomic data to develop true personalized medicines. Focusing on genomics alone without giving consideration to other factors that affect patient outcomes could lead to "depersonalized" medicine, they warn, adding that an "emphasis on personal attributes of patients and their environments, and to incorporate these features into an enriched approach to personalized medicine" is needed to "complement the power of genomics."

March 08, 2013

Technical Tweaks

After making a big splash at the 2012 Advances in Genome Biology and Technology meeting in Marco Island, Fla., Oxford Nanopore kept fairly mum this year, as our sister publication In Sequence noted, citing arbitration and technical issues as possible causes.

Indeed, the company has been facing technical setbacks, blogger Nick Loman from Birmingham University writes at Pathogens: Genes and Genomes, drawing on a barroom conversation with Clive Brown, the company's chief technology officer, at AGBT.

The MinIon's senor chip wasn't working as the company liked, so that component had to be re-designed. "That put us back about 5 months, but it was the right thing to do," Brown told Loman. Loman also reports that the company is also working on keeping the lipid bilayer it uses from degrading and on reducing its error rate to 1 percent. Last year, as In Sequence reported at the time, the company announced it had a 4 percent error rate.

Oxford Nanopore declined to comment further, but did not deny any information from the blog post, saying it should have made it clearer that parts of the conversation were off the record, as it did with other news organizations.

Brown further expressed frustration to Loman that he and his company are repeatedly asked by both the community and the media about why they have not released data nor met their anticipated 2012 commercialization goal. Brown added that data from the company's early-access program should come out this year.

March 07, 2013 / 3 comments

After the Cancer Genome Atlas

The Cancer Genome Atlas is set to finish up next year after sequencing some 10,000 samples from about 20 different cancer types. TCGA has found, ScienceInsider notes, a number of new cancer genes and confirmed others that were previously identified. But with its price tag reaching over $375 million, some critics say it has been too expensive, though many disagree.

At a National Cancer Institute meeting earlier this week, Louis Staudt and Stephen Chanock discussed what could be a next step — by sequencing even more samples, say 10,000 per tumor type, researchers could uncover rare variants contributing to the disease, ScienceInsider adds. Further, it could enable studies examining the interplay of genetics and environmental factors.

However, with the agency facing a 5 percent budget cut, such a grand project might not be realized. ScienceInsider also notes that some skeptics said that the project might reach a level of "diminishing returns." According to ScienceInsider Cold Spring Harbor Laboratory's Bruce Stillman noted that he is a supporter of TCGA, but that taking it to such a new scale "is not very sensible at the moment."

March 07, 2013 / 1 comment

Special Look

Sexism unfortunately still exists in science in the US and Europe, begins an editorial in this week's special issue of Nature. While progress has been made to combat sexism, it appears to have stalled — women in the US and Europe earn about half of all the science doctoral degrees awarded, yet make up about a fifth of full professors, the editorial adds. Practical issues like childcare likely hinder the careers of many women, but there is "a second, more insidious major problem: overt or unconscious gender bias," the editorial says.

In a separate article, Jennifer Raymond, a Stanford University neurobiologist, writes that most people associate men with science and careers and women with liberal arts and family, and points to the recent PNAS paper from Jo Handelsman at Yale University that showed that researchers were more likely to hire a male undergraduate laboratory manger over a female one, even if their CVs were identical. The female applicants were also offered a smaller salary.

"There is now sufficient evidence to move us beyond the denial phase of dealing with gender bias. Yet in talking to colleagues around the world, I find continued resistance to the idea that scientists, who take pride in being rational and objective, could be influenced by bias," Raymond says. She offers ways for researchers, and others, to work to overcome their biases, such as using a gender-blind review or to consciously mentor female scientists.

Also in Nature, Brigitte Mühlenbruch from the European Platform of Women Scientists and University of Duisburg-Essen's Maren Jochimsen write that broad changes are needed to bring equality to science. "To achieve lasting equality, science needs a culture that is sensitive to gender and diversity in all its endeavours: individual and social, structural, institutional and political," they write. "We need transparency, accountability and monitoring in decision-making, evaluation, recruitment, attribution and funding. We need to secure the interest and collaboration of highly qualified women and men by offering predictable academic careers, attractive working places and conditions that enable work and life to be reconciled."

Other aspects of the special issue focus on women in biotech, equality for female scientists around the world, equality at journals, and more.

March 07, 2013

This Week in Nature

In Nature this week, a team from Wageningen University reports on the identification of a gene that regulates the initiation of tuber development and plant maturity in potatoes. The plant originated in the Andes and evolved short day-dependent tuber formation as a propagation strategy. In more northern latitudes such as the US and Europe, potatoes needed to adapt to being grown in long-day conditions. The researchers identified a gene responsible for early tuberization in such an environment and suggest that the trait helped form the basis for the plant's domestication in northern countries.

Meanwhile, in Nature Genetics, researchers from the University of Michigan describe newly identified genetic variants associated with age-related macular degeneration. They conducted a meta-analysis of genome-wide association studies for the disease, including over 17,000 individuals with advanced AMD and 60,000 healthy controls. They found seven genomic regions newly associated with AMD risk and 19 associated regions overall, providing "new directions for biological, genetic and therapeutic studies of AMD."

Our sister publication GenomeWeb Daily News has more on this report here.

March 07, 2013

The Proteoform

In correspondence to Nature Methods, Lloyd Smith, Neil Kelleher, and the Consortium for Top Down Proteomics suggest the term "proteoform" to describe all the shapes that a protein can assume. "Given the importance of capturing this protein variation in basic and translational research, and that technologies now exist to reveal it, we point out an ongoing problem in nomenclature regarding what to call it," they write.

Smith and his colleagues add that many of currently used terms are imprecise — 'isoform' actually refers to genetic, not protein, variations, while the phrase 'protein species' cannot "distinguish between proteins originating from different genes and those originating from a single gene."

'Proteoform', they say, will help solve these issues, and they have begun using it in their work. "We find it to be intuitive and readily grasped by readers and audiences. It has an aesthetic appeal, as the simple protein analog of the genetic term 'isoform'," they add.

"It just catches on … it fills a void the rolls right off the tongue at conferences and sits well in the gut while digesting text," Kelleher tells Nature Methods' Methagora blog.

March 06, 2013 / 1 comment

Rebuilding and Reflection

Researchers at New York University's Langone Medical Center are working to restore their mouse colonies following their loss during Hurricane Sandy, reports the Associated Press. The storm caused flooding of the medical center's basement where the animals (as well as the building's emergency generators) were housed. Shortly after the storm, NYU neurobiologist Gordon Fishell told the Nature News Blog that he'd lost 40 strains of mice, or 2,500 individuals, but that his colleagues in the region had been in touch, telling him they'd help him rebuild.

Such rebuilding is underway, the AP adds, but it will take time. "But it's not as easy as just shipping mice to New York. The mice at NYU live in a super-clean environment, and those imported from other labs carry a risk of contamination," the AP notes. "So scientists use them to create a new generation of animals that are quarantined and checked for germs before they enter their NYU home."

Sergei Koralov says he lost about 600 mice that he was using to study genetic changes in white blood cells and how those changes related to lymphoma development. While he is rebuilding his mouse colonies, he is also taking another look at his research. "The silver lining of the whole storm, what little there is, is the fact it allows me to refocus myself," he tells the AP. Koralov plans to "go after what is interesting to me now, not what was interesting to me two years ago."

March 06, 2013

Oxford Nanopore Chip Sighting

While the next-generation sequencing world ponders the existence of Oxford Nanopore's sequencers, James Hadfield writes on his blog that he caught sight of a sequencing chip for the instrument recently.

On his CoreGenomics blog, Hadfield says that while at the Science Museum in London this past weekend, he was "amazed" to see the chip on display in the "Who Am I" gallery. Next to the chip is a description of the chip that reads, "Oxford Nanopore chip. Tiny pores 10,000 times smaller than a human hair sit in microscopic holes covering the surface of this speedy chip. DNA is read electronically as it zips through each pore, generating DNA sequence data."

Hadfield, who runs the genomics core facility at Cambridge Research Institute, also notes that the chip is next to a Life Technologies SOLiD sequencer. "Don't read [too] much into it being next to a technology that is already obsolete!" he says.

Oxford Nanopore, of course, sent a shiver through last year's Advances in Genome Biology and Technology meeting when it announced two nanopore strand sequencing systems, GridIon and MinIon, that the UK company said would deliver very long reads with high speed and accuracy, as Daily Scan's sister publication In Sequence reported at the time.

Since then, however, the company has been relatively quiet and at this year's AGBT meeting, the firm was a phantom, opting not to provide an update on the technology, In Sequence said.

March 06, 2013

Nancy Kelley Leaves the New York Genome Center

Nancy Kelley is leaving her founding executive director post of the New York Genome Center, Bio-IT World reports. According to a press release, Kelley "was a key driving force behind the creation and growth of NYGC," the aim of which is to strengthen genomics research in the New York City area.

Kelley will stay as an advisor and a member of the center's board of directors. "Working with the New York Genome Center and all of its supporters and partners has been an extraordinary experience," Kelley says in a statement. "This is an exciting time in science and medicine. The Center is now well positioned to become a world-class collaborative center for translational genomic research."

NYGC recently announced that Rockefeller University's Robert Darnell will serve as its first president and scientific director, as our sister publication In Sequence has reported.

March 06, 2013

This Week in Nucleic Acids Research

George Church and company have cooked up a scheme for harnessing components of the bacterial "clustered interspersed short palindromic repeat" and "CRISPR-associated" system — normally used in adaptive immunity — to aid in genome engineering efforts using the budding yeast Saccharomyces cerevisiae. As they report in the online edition of Nucleic Acids Research, the researchers relied on RNA-guided endonuclease activity offered by components from the type II CRISPR-Cas system. Using a Cas9 gene together with a designer guide RNA, they found that they could target double-stranded DNA breaks in the yeast genome, ratcheting up rates of homologous recombination with donor oligos.

Negative strand genomes generated during hepatitis C virus replication appear impervious to RNA interference by short hairpin RNAs active against the original HCV genome, according to a study by a Stanford University team. After narrowing in on short hairpin RNAs with activity against conserved bits of the RNA-based HCV genome, researchers designed corresponding shRNAs aimed at the virus's "antigenome." Their results suggest such negative strand targets are not vulnerable the shRNAs — a realization that study authors study say should "provide new insights into HCV biology and have important implications for the design of more effective and safer anti-viral RNAi strategies seeking to target HCV and other viruses with similar replicative strategies."

Finally, a group from China and the US describes a methylation sequencing method it used to compare 5-hydroxymethylcytosine profiles in mouse embryonic stem cells with those in neural progenitor cells. The strategy — known as hydroxylated DNA immunoprecipitation sequencing, or hMeDIP-seq — allows for simultaneous analyses of several barcoded DNA samples that are handled in a single hMeDIP reaction, the researchers note, offering what they call a "cost-effective and user-friendly strategy for direct genome-wide comparison of DNA hydroxymethylation across multiple samples."

March 06, 2013