Up-and-Comers

It's only a few months into the year, but MIT's Technology Review has put together a list of 10 "breakthrough technologies" for 2013. "Our definition of a breakthrough is simple: an advance that gives people powerful new ways to use technology," the Tech Review editors write.

On that list, nestled between temporary social media (think Twitter messages that can expire) and additive manufacturing (those 3D printers everyone is talking about) is prenatal DNA sequencing. Tech Review notes that, in the US, four companies currently offer non-invasive prenatal genetic screens and, highlighted by Illumina's takeover of Verinata, full-genome sequencing of fetuses is likely coming down the pike, though there are cost and ethical issues to consider.

"We are going to face the challenge of what do you look for and how do you counsel women," Dennis Lo from the Chinese University of Hong Kong tells Tech Review. "I think we must use the technology in an ethical fashion and should refrain from analyzing things that are not life-threatening. Like predisposition to diabetes when someone is 40 years old. We don't even know what medicine would be in 40 years, so why worry the mother about that?"

This Week in Cell

University of Massachusetts researcher Albertha Walhout and colleagues describe diet-related gene expression networks delineated multiple genetic screening methods. The group used a mutagenesis screen, RNA interference, and other approaches to track down a gene network involved in dietary response when Caenorhabditis elegans worms munch on Comamonas bacteria rather than their standard Escherichia coli fare. Through analyses of this set of 146 apparent activators and 38 repressors, the study authors unearthed "a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus."

German researchers report on findings from an RNA interference-based search for genetic factors involved in liver regeneration. The team used small hairpin RNAs to systematically knock down genes in a mouse model of liver regeneration, looking for targets that enhanced or suppressed this liver regeneration. The search led them to a kinase-coding gene called MKK4 that seems to have a central regulatory role in liver regeneration. This process got a boost in mouse models when the gene is silenced, researchers found, even when underlying acute or chronic liver disease was present.

The succession of players that come together in protein complexes appears to be under evolutionary selection, according to a UK team, suggesting this assembly order contributes to biological function. The researchers considered protein assembly in general and in the context of proteins produced from fused genes. With the help of genome sequence data, for example, they found evidence that protein assembly pathways tend to be conserved in the face of gene fusion events. These and other data "reveal the intimate relationships among protein assembly, quaternary structure, and evolution," study authors say, "and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways."

Bicycles, Prosthetic Arms, and Diagnostics

At the White House science fair yesterday, US President Barack Obama hopped on a bicycle and pedaled to power a water filtration system devised by Kiona Elliott and Payton Kaar from Northeast High School in Florida that is designed to be used during an emergency — the pair was influenced by the aftermath of the 2010 earthquake in Haiti, the Associated Press reports. Other science projects included a prosthetic arm made using a 3D printer, pads to help football players keep cool on the field — which Obama called "pretty spiffy," according to the AP — and a fast and cheap way to diagnose pancreatic cancer.

The White House also announced new initiatives to encourage kids to study science, technology, engineering, and mathematics, the New York Times reports. One effort is the creation of an AmeriCorps program that places volunteers with STEM-related nonprofits, while another is a corporate mentoring campaign called US2020 formed by tech companies like SanDisk and Cisco, the Times adds.

In addition, the Times notes, Obama's 2014 budget proposal includes $180 million to increase opportunities from kindergarten through graduate school to participate in STEM programs as well as $265 million for groups focused on STEM education, including school districts, science agencies, and museums, and $80 million for training 100,000 new math and science teachers during the next 10 years.

"This is not the time to gut investments that keep our businesses on the cutting edge, that keep our economy humming, that improve the quality of our lives," Obama said in remarks yesterday.

Powered by E. Coli

By adding genes from a variety sources — including other microorganisms and the camphor tree — researchers have coaxed Escherichia coli to produce diesel, Scientific American's David Biello reports.

As John Love from University of Exeter and his colleagues write in the Proceedings of the National Academy of Sciences, they engineered E. coli to metabolize fatty acids into different hydrocarbons by inserting a Photorhabdus luminescens fatty acid reductase complex along with aldehyde decarbonylase from Nostoc punctiforme, a thioesterase from Cinnamomum camphora, and the branched-chain α-keto acid dehydrogenase complex and β-keto acyl-acyl carrier protein synthase III from Bacillus subtilis.

The E. coli were fed sugar and yeast extract and could produce diesel, which it appears to be able to expel from the cell through an unknown mechanism.

"We wanted to make biofuels that could be used directly with existing engines to completely replace fossil fuels," Love tells Biello. "Our next step will be to try to develop a bacterium that could be deployed industrially."

Meanwhile, In Another Court

Gene patenting isn't just a big case in the US: Australia's Full Federal Court is also considering the validity of patents held by Myriad Genetics and Genetic Technologies, a Melbourne-based firm, on isolated gene sequences associated with breast and ovarian cancers, ScienceInsider reports.

Similar to the US, one of the issues the Australian court is considering is whether isolated DNA is different than naturally occurring DNA and if it is eligible to be patented, ScienceInsider adds. A federal court found in February that the patents were valid, with the judge saying that while DNA and RNA found naturally in the cells of the body were not patentable, because isolating the sequences needs human intervention, those sequences are an invention and can be patented. Opponents, led by Sydney law firm Maurice Blackburn's Rebecca Gilsenan, are appealing the case

At the same time, ScienceInsider notes, Australia is moving to change how it handles biomedical patents. A new law, which went into effect last week, "streamlines patent and trademark procedures, raises the standards on patent eligibility, and improves trademark and copyright enforcement, it does not deal with … the patentability of genetic material," it writes.

This Week in PNAS

Columbia University's Ian Lipkin led an international team that unearthed dozens of hepaciviruses and pegiviruses in bats. As they report in the early, online edition of the Proceedings of the National Academy of Sciences, the researchers started with an RNA sequencing-based look at viral diversity in blood samples from more than 400 African and Central American bats. When they tossed out host sequences and compared the remaining reads with RNA and amino acid databases, investigators identified various viral representatives from the Flaviridae family. Among them: representatives from the Hepacivirus and Pegivirus genera that contain hepatitis C and related GB viruses, respectively. Follow-up experiments in more than 1,200 samples from bats in seven countries indicated that a significant proportion of bats — almost 5 percent of those tested — carried hepaciviruses and/or pegiviruses.

An international team led by investigators at the University of California, Davis, describes a new four billion base physical map for Aegilops tauschii — a diploid plant with a genome that's thought to correspond to the hexaploid wheat plant's "D genome." Using an Ae. tauschii SNP array and contigs assembled from fingerprinting information on hundreds of thousands of bacterial artificial chromosomes, researchers put together a 4.03 billion base physical map for Ae. tauschii. Through comparisons with sequenced plants, authors of that study gained insights into gene density, disease resistance gene profiles, recombination, chromosome structure, and other features related to grass plant evolution.

Finally, for another study slated to come out online this week in PNAS, researchers from Cornell University outline a single-molecule analysis strategy that they are using to tally up multiple epigenetic marks in combination with one another. The "single chromatin molecule analysis in nanochannels," or SCAN, approach centers on a nanofluidic manipulation of bits of chromatin with fluorescent labels recognizing methylated DNA and other epigenetic marks, study authors explain. In the new study, for example, they demonstrated that this method could assess combinations of epigenetic marks in both normal and cancerous cell lines.

To Be Precise

Medical institutions across the US are investing in large centers, new technology, and more experts to bring precision medicine — the new personalized medicine — to the clinic, especially to cancer patients, the New York Times reports. While the expectation is that, eventually, every patient will undergo genomic sequencing, "even optimists warn that medicine is a long way from deriving useful information from routine sequencing," the Times says. And it is an expensive endeavor that is rarely covered by insurance.

The institutes, it adds, are busy collecting data, noting that Memorial Sloan-Kettering Cancer Center sequenced 16,000 tumors in 2012 and Mount Sinai has collected information from 24,000 patients that it is storing in an electronic "biobank" and analyzing with its Minerva supercomputer.

Other centers are watching this unfold. James Crawford from Hofstra North Shore-LIJ School of Medicine says his institute is weighing joining the game or waiting for data. "What is the ultimate utility of this personalized medicine?" he tells the Times. "As a medical profession but also as a society we have not answered this question to our satisfaction."

Conflicted Reports

BMC Genomics has issued an expression of concern regarding a 2011 article on an adaptive role for subfunctionalization in modulating the effect of gene dosage, Retraction Watch reports. According to a statement from the journal, one of the institutions to which first author Ariel Fernandez was affiliated found that the data he generated was not reproducible while a second institution he was associated with did not find anything wrong with the methods or data. "Given the conflicting conclusions of these investigations, the Editors advise the readers to interpret the data with due caution," the statement says.

Retraction Watch notes that Fernandez was affiliated with the National Research Council of Argentina, the University of Chicago, and the Morgridge Institute for Research in Wisconsin.

Drawing on the Young

BGI is divided into a number of parts, and all of them are powered by young researchers and staff, Bioentrepreneur's Trade Secrets blog writes. BGI, it says, has more than 4,000 employees spread across its different parts, including BGI Research, BGI Tech, BGI Healthcare, and BGI Agriculture as well as spinoff companies and a college.

Wang Jun, the executive director of BGI, tells Trade Secrets that the average age of a scientist there is 23 and the average age across the company is 26, as it plucks people straight out of college. "There is no existing talent; they all have to be trained," Wang says. "And the best way to train them is to recruit them from the top universities and to throw them into real projects. The ones who have more experience, you need more creative thinking from them, instead of just training them what to do."

This, the blog adds, mirrors the strategy that some dot-com companies took, saying that "in a competitive and fast-paced field like genomics, having the best — and most energetic — talent on your team is the best strategy to keep hitting winners."

This Week in PLOS

A University of California, San Francisco-led team interrogated SNPs in 17 candidate genes as part of its search for genetic and other factors contributing to lymphedema risk in women treated for breast cancer. As they report in PLOS One, the researchers unearthed lymphedema-associated variants in four lymphatic and/or blood vessel formation-related genes after testing more than 150 breast cancer patients with lymphedema and 387 breast cancer patients without the lymphatic blockage condition. Along with the apparent risk variants, the team notes that women with more lymph nodes removed during treatment appeared to be at higher-than-usual lymphedema risk. So, too, were those who were heavier and/or had later stage breast cancers.

In PLOS Genetics, researchers from Ireland, the UK, Canada, and France describe findings from a genome sequencing-based analysis of Salmonella enterica. By sequencing 73 isolates of a S. enterica serovar called Agona — collected during five foodborne infection outbreaks, from individuals or animals with sporadic infections, or from environmental sources — the team delved into details of past outbreaks and tallied up genetic diversity in the gastroenteritis-causing bug. For instance, their results suggest the outbreaks considered in the current study involved genetically different versions of S. enterica. Even so, outbreak strain diversity appeared to be lower than that predicted by pulsed-field gel electrophoresis, which seems to pick up variation in the bug's accessory genome rather than from core sequences containing outbreak-related determinants.

The simian Treponema strain Fribourg-Blanc is most genetically similarly to the T. pallidum sub-species that causes yaws in humans, according to a study in PLOS Neglected Tropical Diseases. Investigators from Masaryk University in the Czech Republic and Washington University School of Medicine generated a high-quality genome sequence for the Fribourg-Blanc strain. When they compared the genome sequences for representatives from the T. pallidum sub-species that cause syphilis (pallidum) or yaws (pertenue), researchers found that the Fribourg-Blanc strain clustered most closely with the yaws-causing pertenue sub-species. "[W]e propose to rename the unclassified simian isolate to T. pallidum ssp. pertenue strain Fribourg-Blanc," authors of the study say, noting that "non-human primates could serve as possible reservoirs of [yaws-causing] strains."

FDA for "2 Cents a Day"

In front of the Senate appropriations subcommittee yesterday, US Food and Drug Administration Commissioner Margaret Hamburg said the agency is a "true bargain" among federal agencies, at a cost of about two cents a day or eight dollars a year for each American.

Reuters reports that Hamburg appeared before the committee to ask for more money in the face of mandatory cuts of about $209 million to the agency budget as part of the sequester.

The FDA gets only a small part of its funding from taxpayers, with most of its budget filled by user fees paid by drug and other companies that submit products for review. The sequester is set to withhold a portion of these user fees.

According to Reuters, Hamburg argued to the committee what she told Massachusetts Biotechnology Council annual meeting attendees — that such fees should be exempt from the cuts, and that the FDA "will not always be able to complete its review of new drug applications on the agreed upon schedule," without them.

According to Hamburg, the FDA is doing its best to tighten its belt by cutting back on travel and training, but plans to expand its oversight of specialty compounding pharmacies to the tune of $3 million and also needs money to respond to increasing globalization of the food and drug supply chain.

The Microbes You Share

With all the licking and petting, dogs and their owners share microorganisms. Dog ownership, writes Lisa Raffensperger at D-brief, may be a main factor influencing what microbes live on a person's skin.

In a new study, researchers led by the University of Colorado's Rob Knight examined the fecal, oral, and skin microbiota of 60 families with and without children or dogs. As they report in eLife, cohabitating partners shared many microbes, especially Prevotella and Veillonella, but people also had similar microbial communities as their dogs. Dogs, Raffensperger notes, harbor Methylophilaceae bacteria in their mouths that appear to make their way to dog owners' skin.

"It is intriguing to consider that who we cohabit with, including companion animals, may alter our physiological properties by influencing the consortia of microbial symbionts that we harbor in and on our various body habitats, and in particular, our skin habitats," Knight and his colleagues write.

Economics and Serendipity

By now, you've probably read several blog post and articles that make arguments for why research data and software should be free and open to all — we figure one more won't hurt.

In a recent post, an Ensembl outreach officer makes a case for why Ensembl's data and code are open source and open access that is based on economics and chance.

Economically speaking, making everything open saves time, money, and infrastructure and just makes for more efficient research.

"Funders and scientists understand that lots of different labs need the data and the analysis that we produce," the post says. "However, it would be horribly inefficient if each lab who needs the resources we provide had to produce it themselves, repeating work that somebody else has already done, spending money that has already been spent, spending time that they could be spending doing other experiments or doing other analysis."

Also, unrestricted access to data leaves room for surprise discoveries, like the time Alexander Fleming found a fungus or when the Kellogg brothers discovered that stale wheat could be rather tasty.

"If we charged people to use Ensembl in some kind of per-use manner, then they’d only use Ensembl to look for things they knew they were looking for," the author writes. "By allowing people to browse Ensembl freely, without worrying about costs, they may stumble across the tool or data that will be exactly what they need."