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Vaziri N.D.,University of California at Irvine | Wong J.,Lawrence Berkeley National Laboratory | Pahl M.,University of California at Irvine | Piceno Y.M.,Lawrence Berkeley National Laboratory | And 5 more authors.
Kidney International | Year: 2013

The population of microbes (microbiome) in the intestine is a symbiotic ecosystem conferring trophic and protective functions. Since the biochemical environment shapes the structure and function of the microbiome, we tested whether uremia and/or dietary and pharmacologic interventions in chronic kidney disease alters the microbiome. To identify different microbial populations, microbial DNA was isolated from the stools of 24 patients with end-stage renal disease (ESRD) and 12 healthy persons, and analyzed by phylogenetic microarray. There were marked differences in the abundance of 190 bacterial operational taxonomic units (OTUs) between the ESRD and control groups. OTUs from Brachybacterium, Catenibacterium, Enterobacteriaceae, Halomonadaceae, Moraxellaceae, Nesterenkonia, Polyangiaceae, Pseudomonadaceae, and Thiothrix families were markedly increased in patients with ESRD. To isolate the effect of uremia from inter-individual variations, comorbid conditions, and dietary and medicinal interventions, rats were studied 8 weeks post 5/6 nephrectomy or sham operation. This showed a significant difference in the abundance of 175 bacterial OTUs between the uremic and control animals, most notably as decreases in the Lactobacillaceae and Prevotellaceae families. Thus, uremia profoundly alters the composition of the gut microbiome. The biological impact of this phenomenon is unknown and awaits further investigation. © 2012 International Society of Nephrology.

McDonald D.,University of Colorado at Boulder | Price M.N.,Lawrence Berkeley National Laboratory | Goodrich J.,University of Colorado at Boulder | Goodrich J.,Cornell University | And 9 more authors.
ISME Journal | Year: 2012

Reference phylogenies are crucial for providing a taxonomic framework for interpretation of marker gene and metagenomic surveys, which continue to reveal novel species at a remarkable rate. Greengenes is a dedicated full-length 16S rRNA gene database that provides users with a curated taxonomy based on de novo tree inference. We developed a taxonomy to tree approach for transferring group names from an existing taxonomy to a tree topology, and used it to apply the Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB (Cyanobacteria only) taxonomies to a de novo tree comprising 408 315 sequences. We also incorporated explicit rank information provided by the NCBI taxonomy to group names (by prefixing rank designations) for better user orientation and classification consistency. The resulting merged taxonomy improved the classification of 75% of the sequences by one or more ranks relative to the original NCBI taxonomy with the most pronounced improvements occurring in under-classified environmental sequences. We also assessed candidate phyla (divisions) currently defined by NCBI and present recommendations for consolidation of 34 redundantly named groups. All intermediate results from the pipeline, which includes tree inference, jackknifing and transfer of a donor taxonomy to a recipient tree (tax2tree) are available for download. The improved Greengenes taxonomy should provide important infrastructure for a wide range of megasequencing projects studying ecosystems on scales ranging from our own bodies (the Human Microbiome Project) to the entire planet (the Earth Microbiome Project). The implementation of the software can be obtained from http://sourceforge.net/projects/tax2tree/. © 2012 International Society for Microbial Ecology All rights reserved.

Second Genome | Date: 2014-01-03

The disclosure provides methods and systems for characterizing the effects of an agent on one or more microbial communities.

News Article | January 18, 2013
Site: www.wired.com

Ayasdi, a company that has developed data visualization software it says uses big data to answer the questions you never thought to ask, has launched in Palo Alto with $10.25 million in funding. Khosla Ventures and Floodgate are backing Ayasdi, which was founded in 2008 by Gurjeet Singh, Harlan Sexton and Stanford mathematics professor Gunnar Carlsson while researching ways to commercialize Carlsson’s work with scientific data investigation. In 2010, the company received $1.25 million in seed funding to build prototypes of its technology, used with private clients that include US intelligence agency Iarpa, Second Genome, and Darpa to investigate areas such as drug discovery, cancer therapy, fraud prediction and terrorist attack prevention. This latest round of financing officially launches the company into the commercial realm. [partner id=”wireduk”]Their new product is called the Iris Insight Discovery platform. It’s a type of machine learning that uses hundreds of algorithms and topological data analysis to mine huge datasets before presenting the results in a visually accessible way. Using algebraic topology, the system automatically hunts down data points close in nature and maps these out to reveal a network of patterns for a researcher to decipher — any closely related nodes of information will be connected and clustered together, like how a social network arranges its data according to relationship connections. “The answers to today’s most important scientific, business and social problems lie in data,” Singh, Ayasdi’s CEO, said in a statement. “The biggest challenge in big data today is asking the right questions of data. There are so many questions to ask that you don’t have the time to ask them all, so it doesn’t even make sense to think about where to start your analysis. The power of Ayasdi is its unique ability to automatically discover insights — regardless of complexity — without asking questions. Ayasdi’s customers can finally learn the answers to questions that they didn’t know to ask in the first place. Simply stated, Ayasdi is ‘digital serendipity’.” It’s a bold statement, however by using algebraic topology Ayasdi has managed to totally remove the human element that goes into data mining — and, as such, all the human bias that goes with it. Instead of waiting to be asked a question or be directed to specific existing data links, the system will — undirected — deliver patterns a human controller might not have thought to look for. “We don’t necessarily need to treat computers like dumb question-answering machines,” said Singh, “we can actually make them do a lot more work.” Given backer Khosla Ventures’ background in the healthcare sector, we could see Ayasdi shift to a focus in this area if demand ensues from big pharmaceutical companies. It is already in good standing in the field, with one published example showing it revealed insights within eight hours, rather than the usual 100 plus. It has also been used to discover new patterns in historical data. Derrick Harris of Gigaom saw this first hand and has attested to witnessing datasets from 272 cancer patients involving 25,000 genetic markers be analysed and visualised within seconds. This kind of work stands to dramatically reduce the time new drug therapies and alike take to go from the lab, to clinical trials, to the public. Explaining how the data maps work, Harris referred to one red cluster that could, for instance, represent cancer survivors, saying “as researchers dig into this area further, they might find, for example, that none of these survivors underwent chemotherapy and all share a rare genetic that might make them particularly well suited to fight off cancer cells.” The system has also already been tested in areas like sports statistics, however, and has the potential to dramatically overhaul pretty much any field that’s data-based — so, pretty much every field. Whatever its primary use, the technology has impressive roots and stands to make a big impact in the field. Having spent 12 years in R&D at Stanford University, where researchers combined mathematics, computer science and data visualisation to built it, Ayasdi received hundreds of thousands of dollars in early backing from Darpa. The agency’s former director Tony Tether is calling it “one of the top ten innovations developed at Darpa in the last decade” and “the key to unlocking some of the biggest national security challenges that we face today.” That’s a big thumbs up, considering the astonishing number of inventions and theories put forward by Darpa in recent years. In a statement, the service also received high praise from the Icahn Institute of Genomics and Multiscale Biology at Mount Sinai and the University of California, San Francisco Brain and Spinal Injury Centre, which have both already used it to uncover data patterns in research.

News Article | June 25, 2015
Site: www.xconomy.com

If you’re an investor anticipating the potential $100 million-plus IPO of microbiome company Seres Therapeutics, your wait should be over before the weekend comes. If you’re a patient with a terrible bacterial infection in your gut anticipating Seres’ lead product, you’ll probably have to wait at least a couple more years. But that doesn’t mean you have to wait for a treatment. OpenBiome of Medford, MA, is already treating about 150 people a week for antibiotic-resistant Clostridium difficile infection, a nasty bug that is raising red flags around the world and kills as many as 29,000 people every year in the U.S. alone. But OpenBiome is no hard-charging, venture-backed startup. It’s a nonprofit stool bank, a repository of public poop that its officials—although there’s little “official” in the demeanor of the young researchers and doctors from the U.S., Canada, and the U.K. who run it—say has two missions: to bring low-cost treatment to C. difficile patients who desperately need it, and to contribute to the fast-growing body of research on the human microbiome. The microbiome, for those unfamiliar, is the collection of trillions of bacteria and other microbes on and in every human body. Its role in human health is a subject of intense research, and early returns already show a tight connection to a healthy gastrointestinal microbiome population and the ability to ward off things like C. diff, which takes over—sometimes with deadly effects—when the host’s regular microbial balance is thrown off by too many antibiotics, chemotherapy, or other disruption. Startups such as Second Genome of South San Francisco, CA, and Vedanta Biosciences of Boston, MA (partnered with Johnson & Johnson) are testing ways to re-balance the microbiome in people with immune-related gut disorders. Research into the microbiome’s role in diabetes, obesity, heart disease, and other conditions is also well underway. But Seres hopes to have the first FDA-sanctioned, rigorously developed microbiome product: a secret mix of bacterial spores derived from samples of human feces that, when swallowed, bloom into a healthy community in the gut and leave no room for C. difficile. Its early clinical data were excellent, with 26 of 30 people whose infection wasn’t responding to antibiotics showing no recurrence of the debilitating diarrhea that C. diff causes. Just recently the FDA gave Seres’ lead product SER-109 a “breakthrough” designation, which ensures a speedier review for the treatment than it would have otherwise. Venture backers have been generous, too, with more than $130 million poured into the company—about half of it from international food giant Nestle. But its Phase 3 plans, which the company said late last year would start in 2015, have been pushed back. Its regulatory documents now say a Phase 3 trial would likely begin in 2016. (An 87-person Phase 2 trial is currently underway.) That could put FDA approval roughly two years away, although the breakthrough designation might speed things up if all goes well. Meanwhile, OpenBiome, fueled by charitable donations, has spent a fraction of what Seres has raised to build safety checks into its collection and distribution system. The treatment it provides—fecal microbial transplantation, or FMT—also relies on charitable donations: the poop of healthy volunteers, which OpenBiome minimally processes, stores in freezers (pictured), and ships to more than 300 hospitals and clinics around the country to give to people with infected guts. Chief medical officer Zain Kassam says with OpenBiome’s stringent standards—30 tests from blood and stool, a waist measurement, body mass index, and a face to face interview—only three of 100 potential donors are allowed to, well, donate. “We have to be extremely conservative,” says Kassam. The weight-related measurements, for example, are to rule out the speculative possibility that obesity and other metabolic problems could be passed from donor to recipient. (An oft-cited study showed the microbiome of obese people caused skinny mice to gain weight.) OpenBiome’s typical donor, then, lives in the Boston area and is young and skinny, with a mean age of 26 and body mass index of 23.3. “It’s often people who really like going to the gym,” says the nonprofit’s executive director James Burgess—which, he acknowledges with a laugh, can influence one’s thoughts when seeing a fit person jogging down the street. OpenBiome has already sent out about 4,500 treatments—sorted into different doses for administration either through a nasal tube or a colonoscopy—to hospitals, clinics, and other practitioners of FMT. According to this map, there’s probably a clinic in your state. OpenBiome’s volume is growing … Next Page »

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