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DNA Testing for Food

In the wake of the horse meat scandal, European authorities are asking for meat samples to undergo DNA testing to detect any contamination, but, as the Wall Street Journal reports, testing may not prevent another incident. Testing, it adds, may not catch all contaminants, and it is expensive.

"If a sample is mixed (contains DNA from more than one species) then sequencing for the unknown is not possible," Angela Bromley, the general manager of Genon Laboratories, which performs meat testing, says.

And, the Journal adds, broadening the scope of testing becomes expensive — each test, it says, costs about €400, or approximately $535. "You have to concentrate your resources where the intelligence is, and right now the problem is pork and horse," spokesperson from the UK's Food Standards Authority says.

February 20, 2013 / 5 comments

Old Techs, New Tricks

Researchers and clinicians are justifiably excited about methods like LC-MS/MS and next-generation sequencing making their way into their labs, but, asks Christine Snozek, director of clinical chemistry at the Mayo Clinical Arizona, what about the technicians?

Beyond simply worrying about technical validation of new platforms, lab leaders also need to make sure these new technologies are embraced by their employees, Snozek writes this week on the blog of the National Academy of Clinical Biochemistry.

Otherwise, she says, that shiny new mass spec could end up just "a dusty, expensive box sitting idle in the corner."

"Introducing any form of change is challenging," Snozek writes. "Humans are change-resistant by nature, and this is even more true for those individuals whose personalities are well-suited for the clinical laboratory with its stringent regulations and SOP-driven nature."

Education is key, she says. For instance, technicians might not be excited to switch from a fully-automated platform to LC-MS/MS detection using manual extraction. But if supervisors explain the benefits of the extra work — eliminating metabolite cross-reactivity, for example — their team will probably be more willing to come onboard.

Taking a page from the military, Snozek recommends after-action reviews to help implement new technologies. "As laboratorians, it's easy to forget about the human side of the process," she says, but with a host of new omics platforms making their way to the clinic, it's an important consideration.

February 20, 2013 / 2 comments

Notes for NGS Newbies

Before diving in with both feet, next-generation sequencing neophytes might want to take a gander at a post by Dan Koboldt at MassGenomics where he describes his 10 commandments for good next-gen sequencing.

In his post, Koboldt breaks up his instructions into four categories: analysis, publications, data sharing and submissions, and research ethics and cost.

His list includes some oft repeated warnings. For example, he cautions against reinventing the wheel when it comes to developing analysis software, and, for pity's sake, don't invent any more words that end in "ome" or "omics."

Some other no-no's, according to Koboldt, include publishing results before they've been vetted properly, testing new methods on simulated data only, and taking "unfair advantage of submitted data."

He also admonishes newcomers to think a little bit about the cost of analysis without which "your sequencing data, your $1,000 genome, is about as useful as a chocolate teapot," and to have a care for the privacy of their study participants' samples and data.

February 20, 2013

The 'Breakthrough' Prize

A new Breakthrough Prize in Life Sciences has been awarded to 11 scientists, according to a press release from the Milner Foundation. The prize is sponsored by Genetech's Art Levinson, Google's Sergey Brin, Anne Wojcicki from 23andMe, Facebook's Mark Zuckerberg and Priscilla Chan, and Yuri Milner, the founder of Mail.ru Group.

Eleven researchers have been named this year's recipients of the award and its $3 million prize. Those researchers are: Rockefeller University's Cornelia Bargmann, David Botstein at Princeton University, Lewis Cantley from Weill Cornell Medical College, the Hubrecht Institute's Hans Clevers, Napoleone Ferrara at the University of California, San Diego, Titia de Lange, also at Rockefeller, the Broad Institute's Eric Lander, Memorial Sloan-Kettering Cancer Center's Charles Sawyers, Bert Vogelstein at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, MIT's Robert Weinberg, and Shinya Yamanaka from Kyoto University.

Each year's winners will also serve on the selection committee.

"I believe this new prize will shine a light on the extraordinary achievements of the outstanding minds in the field of life sciences, enhance medical innovation, and ultimately become a platform for recognizing future discoveries," Levinson says in a statement.

February 20, 2013

This Week in Genome Research

The University of Washington's Jay Shendure and colleagues describe an approach for finding low frequency variants, while reining in sequence errors. This "single molecule molecular inversion probe," or smMIP, assay combines single molecule tagging with molecular inversion probe-based multiplexed targeted capture, they say. In their Genome Research study, for instance, investigators used smMIP on eight cell lines and 45 clinical cancer samples, targeting 33 clinically informative genes apiece. The approach picked up mutations at down to the 1 percent frequency level with 83 percent sensitivity, prompting those involved to argue that "smMIP will be broadly adoptable as a practical and effective method for accurately detecting low frequency mutations in both research and clinical settings."

For more on the method, check out the latest issue of our sister publication, In Sequence.

Complex breakpoints are common in cancer genomes, according to a study by researchers at the University of Virginia and elsewhere. Using a paired-end mapping algorithm called HYDRA-MULTI, the team tallied up breakpoints in 64 cancer samples using matched tumor and normal sequence data generated for The Cancer Genome Atlas. From mapping patterns for nearly 6,200 somatic structural variant breakpoints, the investigators determined that three-quarters of the tumor genomes housed one or more complex clusters of breakpoints. Their subsequent analyses suggest that many of the complex rearrangements found in the cancer genomes appeared through lone mutational events — apparently involving a combination of double-strand breaks and non-homologous repair.

Researchers from the Massachusetts General Hospital and Harvard Medical School performed deep sequencing on small RNAs from Caenorhabditis elegans and a few nematode worms from the same genus to explore the evolutionary history of small regulatory RNAs. When it sifted through microRNA, small interfering RNA, and piwi-interacting RNA profiles in the worms, the team saw relatively little conservation at specific siRNAs or piRNAs. On the other hand, C. elegans and the three other worms shared conservation across dozens of miRNA families and in broader features of the siRNA and piRNA pathways.

February 20, 2013

BGI Hunts for Genetic Links to High IQ

The Wall Street Journal reports that China's BGI is sequencing around 2,200 samples of individuals with high IQ in order to identify genes associated with intelligence.

The project is sequencing the genomes of people with IQs of 160 or higher. As the WSJ notes, "the average Nobel laureate registers at around 145." These genomes will be compared with sequences from the general population in the hope of identifying genes linked to high IQ. The scientists expect to have results in three months.

BGI's Zhao Bowen, who is leading the project, acknowledges that the genetics of intelligence is a "controversial topic" in the West, but says "that's not the case in China," where the Shenzhen government is paying for half the project and BGI the other half.

Most of the samples have come from a project led by Robert Plomin, a professor of behavioral genetics at King's College, London, who has collected DNA samples from around 1,600 individuals through a US project called the Study of Mathematically Precocious Youth.

It's worth questioning whether several thousand genomes will be sufficient to identify genes associated with a complex trait like intelligence. As the article notes, citing height as an example, "attempts to find height-related genes didn't yield any reliable hits until the number of DNA samples exceeded 10,000."

However, Stephen Hsu from Michigan State University, a collaborator on the project, tells the WSJ that the fact that the scientists are studying an extreme phenotype — IQs over 160 — will serve as a shortcut for finding intelligence-related genes.

Most of the participants in the study are the cognitive equivalent of people "who are 6-foot-9-inches tall," Hsu says, making it relatively easy to identify IQ-related genes.

February 19, 2013 / 1 comment

A Bird’s Eye View of the NGS Market

CLC Bio has published the results of a survey of researchers in the next-generation sequencing market to find out which sequencers and software are used the most.

The company says it received responses from 708 individuals in 73 countries.

Not surprisingly, they found that Illumina’s HiSeq and MiSeq are the most used instruments with about 34.6 percent and 21.3 percent of respondents, respectively, stating that they use the systems. Meanwhile, Roche’s 454 sequencers got 21.2 percent of the votes and Life Technologies’ Ion Torrent Personal Genome Machine got 11.5 percent of the responses.

In terms of bioinformatics tools, the UCSC Genome Browser has the most use, according to the survey, with 28.9 percent of respondents reporting that they use the program. Next in line is Ensembl tools and then Bowtie with 26.9 and 23.4 percent of the votes, respectively.

Also worth noting is that NGS is being used primarily for whole-genome sequencing — 40.8 percent of the votes — followed by RNA-seq and de novo sequencing with 40.1 percent and 39.8 percent of the votes, respectively.

Of the 708 respondents, about 24.6 percent work in the US, according to CLC. Also, 73 percent of respondents work in academic research while 9 percent work in industry, another 9 percent in government, and 6 percent work in not-for-profit organizations, according to the survey.

February 19, 2013

In a Bind

Earlier this month, our sister publication ProteoMonitor wrote about Massachusetts Institute of Technology researcher Alice Ting and a method her lab had developed combining enzymatic tagging and mass spectrometry for mapping organelle proteomes.

Now, from Retraction Watch, comes word that Ting has retracted a 2010 Cell paper that described an enzymatic tagging approach to image binding of neurexin and neuroligin proteins.

According to the retraction notice published last week in Cell, Ting's former postdoc and first author on the paper, Amar Thyagarajan, falsified data for the publication and, Ting notes, her lab has since been unable to reproduce their original findings.

The notice goes on to state that an MIT investigation found Thyagarajan to be solely responsible for the misconduct and that he declined to sign the retraction

In a note to Retraction Watch, however, Thyagarajan asserts that he was not contacted by Cell about the retraction and that it was done over his objection.

"I stand by the data that was published and the methodology that I developed. I and others have reproduced this method over four years," he writes.

An update to the post, however, notes that Thyagarajan has resigned his position at patent law firm Clark + Elbing, where he worked as a technology specialist.

Ting, meanwhile, notes that her team has found that "with modified constructs and protocols" they now in fact are able to detect binding of neurexin and neuroligin proteins, and that they plan to publish these results in a future paper.

February 19, 2013

This Week in PNAS

A Memorial Sloan-Kettering Cancer Center-led team presents a model for doing integrated analyses of cancer genomes in a study slated to appear online this week in the Proceedings of the National Academy of Sciences. Using data from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas, the researchers demonstrated that their statistical framework — called iCluster+ — accurately classified hundreds of cancer cell lines by sites of origin, subgroup, and so on. In the process, the study's authors explain, the iCluster+ analyses uncovered new drug sensitivity patterns and cancer sub-types, including a newly described colorectal cancer sub-type with lower-than-usual levels of TP53 gene mutation or chromosomal instability.

The University of Texas MD Anderson Cancer Center's Wenyi Wang and colleagues describe family-based variant-calling software designed to find rare Mendelian variants contributing to disease. Along with simulation experiments, the group applied its Family-Based Sequencing — or FamSeq — analytical approach to search for rare variants in whole-genome and targeted sequencing data on 92 samples from 28 families affected by neurodevelopmental disorders or Wilms tumor. By bringing together raw sequencing reads and Mendelian disease transmission patterns, they say, the method makes it possible to see rare variants with potential ties to disease genes while weeding out false-positive de novo variants. For their new analysis, the study's authors also went on to explore factors affecting the extent to which FamSeq improved such variant calls.

An international team led by investigators at Johns Hopkins University School of Medicine report on findings from an RNA interference-based functional genomic screen for kinase enzymes related to retinal ganglion cell survival. The researchers targeted 623 kinase-coding genes in primary mouse retinal ganglion cells using a set of nearly 1,900 small interfering RNAs. The screen unearthed a dual leucine zipper kinase encoded by the DLK gene, while follow-up experiments delineated details of DLK's role in retinal ganglion cell death. Using a rodent model of optic neuropathy, the investigators also identified a small molecule called tozasertib that curbs DLK-mediated retinal ganglion cell death.

February 19, 2013 / 2 comments

Agency Heads Tell Senate Sequester Will Kill Jobs, Cut Grants

Senior Obama Administration leaders last week told the US Senate that the budget cuts caused by the enactment of the sequestration, if an agreement is not reached to avoid the plan, would cut thousands of research grants and lead to the loss of thousands of jobs.

In her written testimony, Department of Health and Human Services Secretary Kathleen Sebelius told the Senate Appropriations Committee that the across-the-board budget cut of around 5.1 percent would "delay progress" on treatments for chronic diseases and would lead to fewer new grants and smaller budgets for some existing programs.

As it is currently constructed, the sequester would cut the entire federal budget by around 5.1 percent, which would amount to around $1.6 billion less for NIH.

"We expect that some existing research projects could be difficult to pursue at reduced levels and some new research could be postponed as NIH would make hundreds fewer awards," Sebelius, who did not attend the hearing, stated in her prepared remarks.

"Actual funding reductions will depend on the final mix of projects chosen to be supported by each institute and center within available resources. With each research award supporting up to seven research positions, several thousand research positions across the nation could be eliminated," Sebelius continued.

National Science Foundation Director Subra Shuresh in his testimony told the committee that his agency would see a reduction of around 1,000 research grants, impacting nearly 12,000 people who are supported by NSF.

Shuresh said that NSF's funding for major equipment purchases and facility construction would drop by around $35 million, "leading to layoffs of dozens of science and technical staff, with larger impacts at supplier companies."

He said that if the sequester does go into effect, his agency would prioritize its existing awards and aim to hold on to the NSF workforce and protect its Science, Technology, Engineering and Mathematics human capital development programs.

Although very few lawmakers on Capitol Hill actually want to see the sequestration happen, if Democrats, Republicans, and the White House are unable to strike a deficit reduction bargain or continue deferring it then the cuts will take effect.

If a deal is struck to cut spending or raise revenues via various means, it appears to be unlikely that the agreement would include much in the way of cuts to discretionary spending, which is a small part of the overall budget, or that biomedical research would be a likely area to be cut.

This is because funding for NIH, NSF, and other science-supporting agencies enjoys quite broad bipartisan support in Congress, and because President Barack Obama regularly emphasizes the importance of investing in research.

In his State of the Union Address last week, Obama said that the sequester cuts would be "harsh, arbitrary," and would "devastate priorities like education, energy, and medical research."

The president specifically pointed to genomics as an industry that has been paying taxpayers back for their federal investments.

"Every dollar we invested to map the human genome returned $140 to our economy — every dollar. Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs; devising new material to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race. We need to make those investments."

February 18, 2013

Billion-Dollar Brain Map

The New York Times reports that the Obama Administration is set to announce a large-scale effort to map the activity of the human brain, promising to do for brain research what the Human Genome Project did for genetics.

The decade-long project, likely to cost billions of dollars, "is expected to be part of the president's budget proposal next month," the Times reports.

While the White House declined to comment about the initiative, four scientists who were involved in planning the project spoke to the paper about it, including Harvard's George Church, who said the concept emerged in a similar fashion to the Human Genome Project.

“The genome project arguably began in 1984, where there were a dozen of us who were kind of independently moving in that direction but didn’t really realize there were other people who were as weird as we were,” he said.

He noted that the Brain Activity Map could provide a much-needed financial boost for neuroscience. “The Human Genome Project was on the order of about $300 million a year for a decade,” he said. “If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck.”

Some are a bit more cautious about comparisons with the Human Genome Project, however. Ralph Greenspan, the associate director of the Kavli Institute for Brain and Mind at the University of California, San Diego, noted that the Brain Activity Map is addressing a "much more intricate question” than the genome project.

Greenspan, who is involved in planning the Brain Activity Map, said that while it was "very easy" to define the goal of the genome project, "in this case, we have a more difficult and fascinating question of what are brainwide activity patterns and ultimately how do they make things happen?”

February 18, 2013 / 1 comment

A Boost for Biology Crowdsourcing

The UK's Biotechnology and Biological Sciences Research Council has earmarked £2 million ($3 million) to support crowdsourcing approaches to "complex, large-scale scientific problems" within the funding agency's purview.

"In recent years crowd sourcing has been deployed to tackle complex problems and to build research community resources," the BBSRC says in its funding announcement. "Examples have seen crowd sourcing use to re-design a protein, perform microscopic analysis of biomedical samples and even search for molecules that could make cancer treatment candidates."

The agency is seeking research proposals that demonstrate "a large and complex problem that lends itself to a crowdsourced solution and that would be difficult to solve in other ways."

Further details about the program are available here.

February 18, 2013

Get to Know Your Genetic Counselor

At the Cleveland Clinic's HealthHub, Charis Eng highlights the role of genetic counselors in the healthcare system.

Eng, who heads the clinic's Genomic Medicine Institute, says that genetic counselors "help make sense of complicated information and translate it into something that can benefit your health and your family’s health in very real ways."

As an example, she recommends working with a genetic counselor to review your family history before deciding which genetic tests may be necessary. "Genetics is not a fishing expedition," she says. "Nobody wants to go through tests they do not need."

She adds that genetic counselors should be contacted before genetic screening as well as afterward, and that they should work with doctors to create personalized health plans for patients.

February 18, 2013