tag:theconversation.com,2011:/global/topics/metagenomics-6490/articlesMetagenomics – The Conversation2021-06-24T20:11:52Ztag:theconversation.com,2011:article/1632582021-06-24T20:11:52Z2021-06-24T20:11:52ZWe found more than 54,000 viruses in people’s poo — and 92% were previously unknown to science<figure><img src="https://images.theconversation.com/files/408090/original/file-20210624-19-j2pxgb.jpeg?ixlib=rb-1.1.0&rect=7%2C0%2C4985%2C3742&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Research published today in <a href="https://www.nature.com/articles/s41564-021-00928-6">Nature Microbiology</a> has identified 54,118 species of virus living in the human gut — 92% of which were previously unknown. </p>
<p>But as we and our colleagues from the Joint Genome Institute and Stanford University in California found, the great majority of these were bacteriophages, or “phages” for short. These viruses “eat” bacteria and can’t attack human cells.</p>
<p>When most of us think of viruses, we think of organisms that infect our cells with diseases such as mumps, measles or, more recently, COVID-19. However, there are a vast number of these microscopic parasites in our bodies — mostly in our gut — that target the microbes that live there. </p>
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<a href="https://theconversation.com/know-your-bugs-a-closer-look-at-viruses-bacteria-and-parasites-49695">Know your bugs – a closer look at viruses, bacteria and parasites</a>
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<h2>Everybody poos (but not all poo is the same)</h2>
<p>There has recently been much interest in the <a href="https://www.sciencedirect.com/science/article/pii/S0092867418302216">human gut microbiome</a>: the collection of microorganisms that live in our gut. </p>
<p>Besides helping us digest our food, these microbes have many other important roles. They protect us against pathogenic bacteria, modulate our mental well-being, prime our immune system when we are children, and have an ongoing role in immune regulation into adulthood. </p>
<p>It’s fair to say the human gut is now the most well-studied microbial ecosystem on the planet. Yet <a href="https://www.nature.com/articles/s41587-020-0603-3">more than 70%</a> of the microbial species that live there have yet to be grown in the laboratory. </p>
<p>We know this because we can access the genetic blueprints of the gut microbiome via an approach known as <a href="https://www.nature.com/articles/455481a">metagenomics</a>. This is a powerful technique whereby DNA is directly extracted from an environment and randomly sequenced, giving us a snapshot of what is present within and what it might be doing. </p>
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<a href="https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408102/original/file-20210624-23-1im1ar9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Biologists estimate there are a few hundred trillion viruses living within and outside our bodies.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<p>Metagenomic studies have revealed how far we still have to go to catalogue and isolate all the microbial species in the human gut — and even further to go when it comes to viruses. </p>
<h2>11,810 samples of poo</h2>
<p>In our new research, we and our colleagues computationally mined viral sequences from 11,810 publicly available faecal metagenomes, taken from people in 24 different countries. We wanted to get an idea of the extent to which viruses have taken up residence in the human gut.</p>
<p>This effort resulted in the Metagenomic Gut Virus catalogue, the largest such resource to date. This catalogue comprises 189,680 viral genomes which represent more than 50,000 distinct viral species. </p>
<p>Remarkably (but perhaps predictably), more than 90% of these viral species are new to science. They collectively encode more than 450,000 distinct proteins — a huge reservoir of functional potential that may either be beneficial or detrimental to their microbial, and in turn human, hosts.</p>
<p>We also drilled down into subspecies of different viruses and found some showed striking geographical patterns across the 24 countries surveyed. </p>
<p>For example, a subspecies of the recently described and enigmatic <a href="https://www.nature.com/articles/ncomms5498">crAssphage</a> was prevalent in Asia, but was rare or absent in samples from Europe and North America. This may be due to localised expansion of this virus in specific human populations.</p>
<p>One of the most common functions we discovered in our molecular field trip were diversity-generating retroelements (DGRs). These are a class of genetic elements that mutate specific target genes in order to generate variation that can be beneficial to the host. In the case of DGRs in viruses, this may help in the ongoing evolutionary arms race with their bacterial hosts.</p>
<p>Intriguingly, we found one-third of the most common virally-encoded proteins have unknown functions, including more than 11,000 genes distantly related to “beta-lactamases”, which enable resistance to antibiotics such as penicillin.</p>
<h2>Linking gut viruses to their microbial hosts</h2>
<p>Having identified the phages, our next task was to link them to their microbial hosts. <a href="https://www.nature.com/articles/nrmicro1793">CRISPRs</a>, best known for their many applications in gene editing, are bacterial immune systems that “remember” past viral infections and prevent them from happening again. </p>
<p>They do this by copying and storing fragments of the invading virus into their own genomes, which can then be used to specifically target and destroy the virus in future encounters.</p>
<p>We used this record of past attacks to link many of the viral sequences to their hosts in the gut ecosystem. Unsurprisingly, highly abundant viral species were linked to highly abundant bacterial species in the gut, mostly belonging to the bacterial phyla Firmicutes and Bacteroidota.</p>
<p>So what can we do with all of this new information? One promising application of an inventory of gut viruses and their hosts is phage therapy. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547374/">Phage therapy</a> is an old concept predating antibiotics, in which viruses are used to selectively target bacterial pathogens in order to treat infections. </p>
<p>There has been <a href="https://www.frontiersin.org/articles/10.3389/fpubh.2020.00144/full">discussion</a> of potentially customising people’s gut microbiomes using dietary interventions, probiotics, prebiotics or even “transpoosions” (faecal microbiota transplants), to improve an individual’s health.</p>
<p>Phage therapy may be a useful addition to this objective, by adding species or even subspecies-level precision to microbiome manipulation. For example, the bacterial pathogen <a href="https://www.sciencedirect.com/science/article/pii/S1075996413000826"><em>Clostridioides difficile</em></a> (or Cdiff for short) is a leading cause of hospital-acquired diarrhoea that could be specifically targeted by phages.</p>
<p>More subtle manipulation of non-pathogenic bacterial populations in the gut may be achievable through phage therapy. A complete compendium of gut viruses is a useful first step for such applied goals. </p>
<p>It’s worth noting, however, that projections from our data suggest we’ve only investigated a fraction of the total gut viral diversity. So we’ve still got a long way to go.</p>
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Read more:
<a href="https://theconversation.com/how-do-viruses-mutate-and-jump-species-and-why-are-spillovers-becoming-more-common-134656">How do viruses mutate and jump species? And why are 'spillovers' becoming more common?</a>
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<p class="fine-print"><em><span>Phil Hugenholtz P.H. is a co-founder of Microba Life Sciences, which is a microbial genomics company
developing microbiome-based diagnostics and therapeutics and offers metagenomic gut
microbiome reports.</span></em></p><p class="fine-print"><em><span>Soo Jen Low does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>You could say there are a ‘crapload’ of viruses in the human gut. Luckily, most of these do not attack our cells, but instead feed on bacteria.Philip Hugenholtz, Professor of Microbiology, School of Chemistry and Molecular Biosciences, The University of QueenslandSoo Jen Low, Postdoctoral Research Fellow, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1401492020-08-14T12:12:13Z2020-08-14T12:12:13ZThe COVID-19 virus can spread through the air – here’s what it’ll take to detect the airborne particles<figure><img src="https://images.theconversation.com/files/352606/original/file-20200812-14-8pkt2r.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C10210%2C4852&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Researchers are working on handheld devices that can signal the presence of SARS-CoV-2 in the air.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/microscopic-view-of-3d-spherical-viruses-royalty-free-image/1213929556?adppopup=true">fotograzia/Moment via Getty Images</a></span></figcaption></figure><p>A growing body of research shows that SARS-CoV-2, the virus that causes COVID-19, can spread from person to person through the air. Indoor spaces with poor ventilation in areas where the virus is prevalent are particularly hazardous.</p>
<p>In the fictional world of “Star Trek,” public health officials and first responders would be able to determine instantly if a space had a dangerous concentration of airborne virus, and any other pathogen, by simply waving around a <a href="https://en.wikipedia.org/wiki/Tricorder">tricorder</a>. </p>
<p>That technology, imagined 60 years ago, is still firmly in the realm of fiction. However, devices that can rapidly detect particular airborne pathogens – including SARS-CoV-2 – are in the works in various research laboratories.</p>
<h2>The air we breathe</h2>
<p>Detection of the presence of airborne virus particles is complicated by the mixture of other particles in the air. The atmosphere includes a large number of floating particles, a significant fraction of which are biological. Typically, with each breath, you <a href="https://www.sciencedirect.com/science/article/abs/pii/0021850294902283">inhale about a thousand biological particles</a>.</p>
<p>These <a href="https://www.routledge.com/Aerosols-Handbook-Measurement-Dosimetry-and-Health-Effects-Second-Edition/Ruzer-Harley/p/book/9780367866112">bioaerosols</a> include live and dead organisms, including viruses, bacteria, fungi, pollen and plant and animal debris. Viruses are the smallest of these particles. They range in size from 10 to 300 nanometers, or millionths of a millimeter. In contrast, red blood cells average about 6 to 8 microns, or 6,000 to 8,000 nanometers, in diameter. Bacteria range from 1 to 4 microns and fungi 5 to 10 microns. Plant and animal debris is generally larger than 10 microns.</p>
<p>Most of these biological particles are not a health concern, because most are bits of plants and animals, including humans. However, it only takes a small number of dangerous microbes to produce a pandemic.</p>
<h2>IDing bad news microbes</h2>
<p>To understand the potential threat from bioaerosols, it’s important to identify the small fraction of problematic or pathogenic microbes from among all the bioaerosols present. Bioaerosol identification begins with capturing biological particles from the air, typically by collecting particles on a filter, in a liquid vial or on hydrogels. </p>
<p>Often, researchers transfer the collected bioaerosols to a culture medium that is designed to support microbe growth. How the microbes respond to a specific culture medium – the size, shape, color and growth rate of the microbe colony – can indicate the microbe species. </p>
<p>This process can take several days to weeks, and is often ineffective. It turns out the scientists can <a href="https://doi.org/10.1111/1574-6968.12487">only identify about 1% of airborne microbes</a> with this approach.</p>
<p>Increasingly, scientists are relying on gene-based analyses to map viruses and other microorganisms collected in air samples. One popular technique for gene-based analysis is polymerase chain reaction (PCR), which uses an enzymatic reaction to make many copies of a specific gene or portion of a gene so that the genetic sequence – DNA or RNA – can be detected in a sample. A PCR test can be designed to spot gene sequences specific to a microorganism so that detecting the sequence equals identifying the microorganism. </p>
<p>This technique is currently the <a href="https://theconversation.com/coronavirus-tests-are-pretty-accurate-but-far-from-perfect-136671">gold-standard for detecting the presence of SARS-CoV-2</a> from nasal swab samples. PCR-based methods are <a href="https://www.intechopen.com/books/synthetic-biology-new-interdisciplinary-science/pcr-and-infectious-diseases">very accurate in identifying pathogens</a>.</p>
<p>Next generation sequencing technology makes it possible to rapidly sequence organisms’ whole genomes. Using these techniques, researchers now have the ability to <a href="https://dx.doi.org/10.1093%2Fgbe%2Fevv064">understand the entire population of microorganisms</a> — their diversity and abundance — in the air.</p>
<h2>Rapid detection</h2>
<p>Despite these advances, there is still <a href="https://www.tandfonline.com/doi/full/10.1080/02786826.2019.1664724">a lot of work to be done</a> to be able to instantaneously identify the presence of pathogens in air. Current techniques for identifying microbes are expensive, require specialized equipment and involve long processing steps. They also can’t detect a species from small amounts of genetic material.</p>
<p>Recent advances, however, provide some promise for the development of <a href="https://doi.org/10.1080/02786826.2019.1664724">sensors that can provide quick information about bioaerosols</a>. </p>
<p>One approach <a href="https://doi.org/10.1038/s41598-019-49005-3">uses laser induced florescence</a>. In this technique, particles are illuminated with light of a particular color or wavelength, and only biological particles respond by fluorescing, or emitting light. This technique can be used to identify and quantify the presence of biological particles in air in real-time but it doesn’t differentiate between a safe and a harmful microbe. </p>
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<img alt="Laboratory equipment containing laser-illuminated tube" src="https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/352604/original/file-20200812-20-31ojns.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Laser-induced fluorescence is a method of using lasers to cause specific substances to emit light.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Fluorescence_in_rhodamine_B.jpg">Jan Pavelka/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Another advance is using <a href="https://doi.org/10.1002/ppsc.200601049">mass spectrometry for bioaerosol detection</a>. In this technique, a single bioaerosol particle is blasted apart with a laser and the molecular fragments are immediately analyzed to determine the molecular composition of the particles. Researchers are also using Raman spectroscopy-based sensors. Raman spectroscopy can identify molecular composition from light reflected off of samples without destroying the samples.</p>
<h2>Big challenge in a small package</h2>
<p>These techniques are advancing instant detection and identification of airborne bacteria and fungi, but they are <a href="https://doi.org/10.1111/1574-6968.12487">less efficient in detecting viruses</a>, including SARS-CoV-2. This is primarily because viruses are very small, which makes it difficult to collect them with air samplers and difficult to perform PCR analysis given the small amount of DNA/RNA. </p>
<p>Researchers are working to address the limitations of detecting airborne viruses. In our lab at Clarkson University, we have developed a low-cost bioaerosol sensor and collector for wide-scale bioaerosol sampling. This battery-operated sampler uses a micro-sized high-voltage source to ionize airborne viruses, bacteria and fungi and collect them on a surface. Ionization gives the biological particles an electrical charge. Giving the collection surface the opposite charge causes the particles to stick to the surface.</p>
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<img alt="small laboratory device connected to laptop via USB cable" src="https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/352605/original/file-20200812-18-1vd2qmr.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Oxford Nanopore Technologies’ MinION is a palm-size DNA sequencer.</span>
<span class="attribution"><span class="source">Courtesy Oxford Nanopore Technologies</span></span>
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<p>Samples from our collector can be analyzed with new <a href="https://doi.org/10.1038/s41598-018-29334-5">portable DNA/RNA sequencers</a>, which allows for near real-time bioaerosol detection with low-cost, hand-held equipment. </p>
<h2>Where’s my tricorder?</h2>
<p>These advances could soon make it possible to detect a known pathogen, like SARS-CoV-2, with a portable device. But they’re still far from being a tricorder. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>For one, they require relatively high levels of a pathogen for detection. Being able to identify a virus like SARS-CoV-2 at lower levels that are nonetheless sufficient for disease transmission will require developing sensors with lower detection limits. Additionally, these sensors can only be tailored to detect specific pathogens, not scan for all possible pathogens.</p>
<p>Though the equivalent of the tricorder in “Star Trek” isn’t around the corner, the need for such a device has never been greater. Now is an opportune time for the emergence of new sensing techniques piggy-backing on the dramatic advances being made in the fields of electronics, computing and bioinformatics. When the next new pathogen emerges, it would be nice to have a tricorder handy.</p><img src="https://counter.theconversation.com/content/140149/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Suresh Dhaniyala is President, Potsdam Sensors, a startup that is commercializing TracB. He has received funding from the National Science Foundation.</span></em></p><p class="fine-print"><em><span>Shantanu Sur has received funding from the National Science Foundation </span></em></p><p class="fine-print"><em><span>Hema Priyamvada Ravindran does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Miniaturized laboratory equipment is making it easier to identify airborne pathogens in the field, but there’s still work ahead to be able to instantly determine if a room is safe or contaminated.Suresh Dhaniyala, Bayard D. Clarkson Distinguished Professor of Mechanical and Aeronautical Engineering, Clarkson UniversityHema Priyamvada Ravindran, Research Associate, Center for Air and Aquatic Resources Engineering and Science, Clarkson UniversityShantanu Sur, Associate Professor of Biology, Clarkson UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1186632019-06-12T21:04:53Z2019-06-12T21:04:53ZRapid DNA analysis helps diagnose mystery diseases<figure><img src="https://images.theconversation.com/files/279009/original/file-20190611-32317-1tby3hy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Decoding all the DNA in a patient's biological sample can reveal whether an infectious microbe is causing the disease.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-method-dna-sequencing-430949605?src=tcYoS2adFzk6wi7ipNkRFA-1-2">ktsdesign/Shutterstock.com</a></span></figcaption></figure><p>As doctors, we deal with a lot of uncertainty. Often, it is difficult to diagnose what is making a patient sick because symptoms from both infectious and non-infectious diseases can be indistinguishable from each other. </p>
<p>The tried-and-true method for clinicians has been to formulate a list of the most likely possibilities – and narrow that list down by ordering a series of tests. However, despite extensive, state-of-the-art testing in hospitals today, we still can’t diagnose approximately 50% of cases of <a href="http://doi.org/10.1056/NEJMoa1500245">respiratory infection</a> (pneumonia), <a href="http://doi.org/10.1186/cc12896">bloodstream infection</a> (sepsis), and <a href="https://doi.org/10.1212/WNL.0000000000000086">neurological infection</a>.</p>
<p>I am an infectious diseases physician and microbiologist at University of California, San Francisco. But in college I specialized in computer science and bioengineering. Because so many of my current patients never end up with a definitive diagnosis, I became interested in applying my skills to leverage emerging sequencing technology and develop a <a href="https://doi.org/10.1101/gr.171934.113">computational pipeline</a> for analysis of DNA sequencing data, with the ultimate goal of providing more accurate diagnoses.</p>
<h2>What is next-generation sequencing?</h2>
<p><a href="https://chiulab.ucsf.edu">My colleagues and I</a> have developed a novel clinical diagnostic test that allows millions of DNA sequences to be decoded from a single clinical sample; for example, a tube of cerebrospinal fluid collected from a hospitalized patient via a lumbar puncture, also known as a “spinal tap.” The aim of this test, called “metagenomic next-generation sequencing” (mNGS), is to diagnose mysterious infections in acutely ill patients. </p>
<p>So far, the bulk of our experience is using this test to diagnose the most severely ill patients with life-threatening infections. However, I envision that as sequencing costs fall, this test could be performed routinely for all patients with suspected infectious syndromes.</p>
<p>This test is called “metagenomic” because DNA from all potential pathogens – bacteria, viruses, fungi and parasites – as well as the patient are simultaneously sequenced. We diagnose likely causes of infection by searching for tell-tale traces of DNA from the causative pathogen. </p>
<p>Currently, the overall turnaround time for the test is 48-72 hours. <a href="https://blogs.biomedcentral.com/on-medicine/2015/09/29/metagenomic-sequencing-diagnose-infectious-diseases/">New sequencing devices</a> may soon make it possible to run this test in less than six hours.</p>
<h2>Precision diagnosis of acute infectious diseases</h2>
<p>For <a href="http://opr.ca.gov/ciapm/projects/2015/Acute_Infectious_Diseases.html">our study</a>, published in the <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1803396">New England Journal of Medicine</a>, we enrolled 204 children and adults from eight different hospitals across the U.S. All of these patients had a mysterious, undiagnosed neurological illness – <a href="https://nextgendiagnostics.ucsf.edu/for-patients/#neurological-conditions">meningitis, encephalitis and/or myelitis</a> – of unknown origin. </p>
<p>To identify the cause we used clinical mNGS testing to identify the pathogens causing the patient’s acute illness.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=316&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=316&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=316&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=397&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=397&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=397&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">mNGS testing for diagnosis of neurological infections.</span>
<span class="attribution"><span class="source">Charles Chiu</span></span>
</figcaption>
</figure>
<p>We ran the mNGS test on cerebrospinal fluid samples from these patients. After analyzing the data we found that in a surprisingly large proportion of infections – 13 of 58, or 22.4% – mNGS testing was necessary to make a timely and accurate diagnosis. </p>
<p>In eight of these infections identified by mNGS only, the diagnosis directly guided doctors to a targeted and appropriate antibiotic treatment. In <a href="https://doi.org/10.1093/ofid/ofx121">one neurological infection caused by hepatitis E virus</a>, the mNGS diagnosis likely spared the patient from a liver transplant. That’s because her hepatitis E infection was treatable with an antiviral drug: ribavirin. Without knowing that the patient’s infection was caused by the hepatitis E virus, this effective drug would not have been considered.</p>
<p>Overall, our study demonstrates the clinical usefulness of metagenomic testing in diagnosing neurological infections. The approach can be used for other types of clinical samples and infections, such as analysis of respiratory samples to diagnose infectious pneumonia. </p>
<p>It is my hope and expectation that this powerful new diagnostic tool will transform the way that we as physicians manage infections in our critically ill patients. This would ultimately lower health care costs and saving lives by virtue of earlier and more accurate diagnoses.</p>
<p>[ <em>Like what you’ve read? Want more?</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=likethis">Sign up for The Conversation’s daily newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/118663/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Chiu's research is supported the California Initiative to Advance Precision Medicine, NIH grant R01HL105704, a UC Center for Accelerated Innovation grant funded by NIH grant U54HL119893 and NIH/NCATS UCSF-CTSI grant UL1TR000004, the Charles and Helen Schwab Foundation, the George and Judy Marcus Innovation Fund, and the Sandler and William K. Bowes, Jr. Foundations.</span></em></p>Superfast DNA analysis is now being used to crack medical mysteries when physicians can’t figure out whether an infectious microbe is causing the disease.Charles Chiu, Professor of Laboratory Medicine, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/809832017-08-04T10:23:16Z2017-08-04T10:23:16ZDNA sequencing and big data open a new frontier in the hunt for new viruses<figure><img src="https://images.theconversation.com/files/181004/original/file-20170804-27452-15t5ivg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Discovering new viruses has historically been biased towards people and animals that exhibit symptoms of disease – like a cough, fever or skin blister.</p>
<p>But there are two challenges to discovering viruses this way. The first is that it’s only the beginning of a long and painstaking process of identifying the infectious virus that caused it. The second more important reason is that it leaves out potentially deadly viruses that might emerge as a result of transmission from other species where they don’t show any clear signs of infection. </p>
<p>HIV or Ebola are examples of this. Both cause humans harm but go unnoticed in their native hosts – monkeys and chimps in the case of <a href="https://www.nytimes.com/2015/03/02/science/two-strains-of-hiv-cut-vastly-different-paths.html">HIV</a> and possibly bats for <a href="http://www.sciencemag.org/news/2017/06/hunting-ebola-among-bats-congo">Ebola</a>.</p>
<p>One possible solution to this is the use of DNA sequencing. The advent of recent technologies has made sequencing DNA faster and cheaper. It has meant that public genome databases now have petabytes – a petabyte is a million gigabytes - of DNA sequence data available from hundreds of species. This so-called next generation sequencing has also given birth to metagenomics, where scientists can scoop up a handful of dirt (or anything else), and sequence everything in it.</p>
<p>This means that scientists can now discover new viruses using DNA sequencing. The magic is that they don’t even have to know what the virus looks like, or if it causes disease. This level of granularity means that scientists can detect miniscule amounts of a virus’s DNA that happens to be in the blood or tissue sample of a host. </p>
<p>Many scientists sequencing the DNA of animals or plants view this viral DNA as a nuisance – rogue contaminants that need to be filtered from DNA sequencing results. </p>
<p>But we took a different view. What if the viral DNA was a missed opportunity? So we set out to test the idea that massive online DNA databases could be used as a resource to discover viruses – even if the data had not been explicitly collected for that purpose. </p>
<p>In <a href="https://academic.oup.com/ve/article/doi/10.1093/ve/vex016/4061468/A-novel-viral-lineage-distantly-related-to">our study</a> we examined 50 genomes of fish and uncovered viral DNA in 15 fish species, including Atlantic salmon and rainbow trout. We did this by applying a data mining approach. Our aim was to identify novel members of a group of herpesviruses – alloherpesviruses – that infect fish.</p>
<p>Our findings have opened up entire new frontiers of understanding about these viruses in fish. To date only a handful have been identified despite the massive growth of the aquaculture industry and potential hazards that emerging infectious disease would cause. This includes economic loss, threat to food supply chains and danger to fish in the wild. </p>
<p>It is yet to be seen if any of the viral sequences identified in 15 different fish are capable of forming infectious viral particles, or if they cause disease. But it’s a start. A major advantage of already knowing the genome sequence of these potential pathogens is that they can be used to help identify the cause of disease.</p>
<h2>New families of viruses</h2>
<p>The key to our approach was to combine evolutionary biology with techniques that are used to analyse huge quantities of DNA sequence data. This strategy has emerged from the new field of <a href="https://paleovirology.com">paleovirology</a> – the study of viruses that have integrated into the DNA of their hosts, sometimes millions of years ago. </p>
<p>We first recognised the potential of using this approach in a study we did in 2014. We went looking for ancient viruses in the <a href="http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004332">Philippine Tarsier</a> and found two modern viruses as well as the ancient herpesvirus. We realised that the technique could be applied to discovering new viruses. </p>
<p>In our latest study we built on the technique to look for novel alloherpesviruses. In fact, we found more than we bargained for. Instead of novel alloherpesviruses, we uncovered a lineage of unusual viruses that may even be a new viral family related to alloherpesviruses. </p>
<p>To confirm that this was not simply a lab contaminant or data processing error, we visited a local supermarket and sushi house for extra samples. Lab work confirmed that fragments are also present in commercial samples.</p>
<h2>Identifying the disease</h2>
<p>Using this approach to identify novel viruses is not yet common practice. But our study demonstrates the value of the data we already have. </p>
<p>There are still gaps in our knowledge: for example, are any of the viral sequences identified in 15 different fish capable of forming infectious viral particles? And do they cause disease? </p>
<p>Even though we can’t yet answer these questions, knowing about the viruses is useful for two reasons: Firstly, we now know about a range of new viruses which could prove useful to the fishing industry. And secondly, while an infectious virus may not even cause disease in its natural host fish, there is a risk of cross-species transmission to other species. As the farmed fishing industry continues to grow there is real possibility of transfer to either other farmed fish or wild populations. The risk of transmitting to humans, however, is far lower. </p>
<p>Beyond this study, we can hunt for novel viruses in a range of different species. One strategy might be to start with culprits that we already know harbour transmissible disease. Bats and rodents, for example, are notorious for being reservoirs of infectious disease that they are seemingly immune to. Insects such as mosquitoes are also carriers of viral diseases (such as Zika) that harm humans. </p>
<p>This development now gives us the scope to apply our approach to uncover other viruses before the next outbreak even happens.</p><img src="https://counter.theconversation.com/content/80983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Amr Aswad does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Massive online DNA databases can be used as a resource to discover viruses – even if the data had not been explicitly collected for that purpose.Amr Aswad, Junior research fellow in virus evolution, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/602082016-06-26T13:53:39Z2016-06-26T13:53:39ZMicrobes in extreme heat and cold hold lessons about life on Earth, and beyond<figure><img src="https://images.theconversation.com/files/127751/original/image-20160622-7194-1ylncc8.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Microbes can survive in the frozen coastal desert soils of Antarctica's Miers Valley.</span> <span class="attribution"><span class="source">Don Cowan</span></span></figcaption></figure><p>Very hot and very cold environments are surprisingly common on planet Earth. Regions of active volcanism, which produce boiling and occasionally super-heated water, are scattered all across the surface of the Earth. These can take the form of hydrothermal pools and deep-sea hydrothermal vents. Cold environments are even more common. The northern and southern polar areas, alpine regions and the deep sea are all examples. These represent the largest single extreme environments on Earth.</p>
<p>For much of the 20th century, these environments were either considered too extreme for life to exist, or they had never been surveyed. In the latter part of the 20th century, the development of modern molecular biology <a href="https://www.youtube.com/watch?v=nCROuCbHDLg">methods</a> led to the surprising discovery that microbes happily inhabit both ends of this extreme temperature scale. These microscopic organisms – mostly bacteria, fungi, archaea and viruses – can survive in boiling water and in the frozen coastal desert soils of the Antarctic continent. </p>
<p>Microbes are not just invisible oddities. They play absolutely critical roles, some negative but many positive, in virtually every part of the world around us. For example, they are responsible for producing a substantial part of the world’s <a href="http://www.microbeworld.org/types-of-microbes/bacteria">oxygen supply</a>. They also supply nitrogen for crop plant growth, help to remove carbon dioxide from the atmosphere and produce most known antibiotics. </p>
<p>But microbes living at the outer edge of biological life can do more than that. They can teach us how life has evolved, how we survive and where we might search for life outside of Earth.</p>
<h2>Mapping the extremes</h2>
<p>Many of the microbes capable of living in boiling water have been isolated. They are grown in laboratories around the world, giving researchers direct access to their cells, their molecules and their products. This makes it easier to address questions about their survival and evolution. </p>
<p>One of the winners in the high temperature growth stakes is a microbe called <em>Pyrococcus furiosus</em>, the furious fire-ball. It was isolated 30 years ago from a shallow submarine hot-spring on a beach in Vulcano Island by the father of high temperature microbiology, <a href="http://www.biologie.uni-regensburg.de/Mikrobio/Stetter/">Professor Karl Stetter</a>. It grows best at 100°C, the boiling point of water. It is one of only a few known microbes that can grow above this temperature. We have learnt a lot from these organisms – most importantly, how evolution has redesigned proteins to withstand very high temperatures.</p>
<p>The big breakthrough that allowed scientists to identify all the microorganisms living in any environment – as opposed to just those grown on a culture plate or in a culture flask – came in the 1980s. In less than a decade, a combination of conceptual, scientific and technical developments all came together. These included the ability to purify total environmental DNA, the development of special marker sequences that can identify different microbial species, and the advent of very fast, very cheap DNA sequencing techniques. </p>
<p>Collectively <a href="http://www.ncbi.nlm.nih.gov/books/NBK54011/">known as metagenomics</a>, these developments hugely stimulated the field of microbiology. They have done so across diverse areas of science, from biological methods for cleaning up environmental pollution and contamination, to human disease. </p>
<p>Modern metagenomics – which can be used to investigate the diversity of microbes in any environment – gives scientists the answers to the simplest ecological questions posed of extreme environments: </p>
<ul>
<li><p>What is there? </p></li>
<li><p>How can these microbes survive extreme temperatures of above boiling or below freezing? Are they more complicated, and do they require the use of complex and sophisticated molecular analyses?</p></li>
</ul>
<h2>The value of ‘extremophiles’</h2>
<p><a href="http://www.up.ac.za/microbial-ecology-and-genomics/">Our research</a> has focused for the past decade on the microbiology of the coldest and driest place on Earth: the Antarctic continent. We have found that despite the extreme climate – there is little or no sunshine for nearly six months of the year and winter temperatures drop below -50°C – coastal desert soils harbour complex communities of microbes. </p>
<p>The mere presence of these organisms, adapted to survive one of the harshest environments on Earth, gives us clues to evolution, adaptation and survival that can be exploited in a range of ways.</p>
<p>Many scientists are fascinated by extreme environments and their microbial communities, and are working to answer basic questions that link the two: </p>
<ul>
<li><p>What microbes inhabit the outer edges of biological life, and how can they survive and grow under such extreme conditions? </p></li>
<li><p>What roles do they play in environmental processes?</p></li>
</ul>
<p>These questions, and their answers, are important. Not only to understand more of the unseen portion of the world around us, but so we can better understand the important part that they play in regulating critically important processes. These processes include oxygen generation and carbon dioxide capture on planet Earth. </p>
<p>There is also great interest in the biotechnological applications of microbes living in these extreme environments, as well as in their production of novel and useful products like pharmaceuticals.</p>
<p>The biotechnology of extremophiles – microbes living in extreme environments – remains a hot topic. We are actively involved in a range of extremophile biotechnology projects. These include:</p>
<ul>
<li><p>the application of high temperature microbes that can use carbon monoxide and water to generate hydrogen gas as a future biofuel – a valuable energy source;</p></li>
<li><p>low temperature microbe genes that can improve cold and drought tolerance in plant species; and</p></li>
<li><p>highly temperature-tolerant enzymes that can assist in the breakdown of plant tissues for use in the production of biofuels and bioproducts.</p></li>
</ul>
<p>In a world of diminishing resources and a growing focus on renewable energy, extremophiles have a valuable role to play in the development of new commercial biotechnology processes.</p><img src="https://counter.theconversation.com/content/60208/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Don Cowan receives funding from various South African sources including the National Research Foundation and the Department of Science and Technology. He is affiliated with the South African Society for Microbiology, The Royal Society of South Africa, the International Society for Extremophiles, the American Society for Microbiological and the International Society for Microbial Ecology. </span></em></p>Microbes have the ability to survive in extremely hot and cold conditions. This makes them invaluable tools for research: they can teach us how life has evolved and how we survive.Don Cowan, Director, Genomics Research Institute; Director, Centre for Microbial Ecology and Genomics, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/480692015-10-27T10:09:45Z2015-10-27T10:09:45ZThe modern, molecular hunt for the world’s biodiversity<figure><img src="https://images.theconversation.com/files/99386/original/image-20151022-8010-1quj9ei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New forms of life are discovered in high-tech ways that leave yesterday's natural history collections in the dust.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic.mhtml?id=114480370&src=id">Detective image via www.shutterstock.com.</a></span></figcaption></figure><p>The news is full of announcements about newly discovered forms of life. This fall, we learned of a <a href="http://phys.org/news/2015-09-frankenvirus-emerges-siberia-frozen-wasteland.html">30,000-year-old giant virus</a> found in frozen Siberia. Until now, known viruses have contained so little genetic information that people have questioned whether they can even be thought of as living. But giant viruses like this one contain as much information as many bacteria, which are certainly alive, and are so big they can be seen with an ordinary microscope. </p>
<p>Earlier this year, we heard that deep in the ocean, by the boiling hot sulfurous vent called Loki’s Castle after the Norse god, a species called <a href="http://www.bbc.co.uk/news/science-environment-32610177">Lokiarchaeota</a> was discovered. It uniquely straddles the three <a href="http://www.ucmp.berkeley.edu/alllife/threedomains.html">domains of life</a>: Eukaryota, including animals and plants; Bacteria; and Archaea, a domain that includes species pumping out methane in your gut right now.</p>
<p>Not only are new life forms being discovered, but so are entirely new ways of living. In the last week we learned of rich communities of bacteria that <a href="http://ucsdnews.ucsd.edu/pressrelease/biologists_discover_bacteria_communicate_like_neurons_in_the_brain">communicate</a> with each other electrically, in the same ways as the neurons in our brain.</p>
<p>The way researchers made these three discoveries illustrates how much the modern study of biodiversity has changed in the last 200 years. Instead of visiting pleasantly warm places with binoculars and a butterfly net, we now look for life in places we never would have before, and we use the same molecular techniques that help catch criminals. </p>
<h2>To boldly go…</h2>
<p>Traditionally, the study of biodiversity was carried out by gentlemen such as <a href="http://www.aboutdarwin.com/timeline/time_04.html">Charles Darwin</a> and <a href="http://www.bbc.co.uk/history/historic_figures/banks_sir_joseph.shtml">Joseph Banks</a>, sailing the high seas of global empires and <a href="https://theconversation.com/why-we-still-collect-butterflies-41485">sending back specimens</a> to be stored in drawers of museums of natural history.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=922&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=922&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=922&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1158&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1158&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99693/original/image-20151026-18443-198c5dz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1158&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Alvin made discoveries of life at depths that had never been visited before.</span>
<span class="attribution"><a class="source" href="http://www.photolib.noaa.gov/htmls/nur07508.htm">OAR/National Undersea Research Program (NURP); Woods Hole Oceanographic Inst</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>For this kind of exploration, out of sight was truly out of mind. Until 1977, we had no idea the ocean floor was home to life at all, never mind rich communities including Lokiarchaeota. They were first discovered by the submersible <a href="http://oceanexplorer.noaa.gov/technology/subs/alvin/alvin.html">Alvin</a> – which wasn’t even looking for life. Its <a href="http://www.divediscover.whoi.edu/ventcd/vent_discovery/">original mission</a> was to study the ocean floor looking for evidence of plate tectonics. As well as finding evidence that the sea floors are spreading, Alvin <a href="http://www.pbs.org/wgbh/nova/nature/life-in-the-abyss.html">sent back images</a> of a rich new ecosystem of completely <a href="http://ocean.si.edu/ocean-videos/hydrothermal-vent-creatures">unknown species</a> fueled entirely by chemical energy, instead of solar energy like all other ecosystems previously known.</p>
<p>A fact we now take for granted is that <a href="http://www.spaceref.com/news/viewnews.html?id=462">wherever</a> we look for life, we find it, including concentrated acids, fluids as corrosive as floor stripper, in <a href="http://www.whoi.edu/oceanus/feature/living-large-in-microscopic-nooks">rock</a> and kilometers beneath the <a href="https://theconversation.com/what-lies-beneath-evidence-of-life-under-the-antarctic-ice-18210">Antarctic ice sheet</a>. It can even <a href="http://www.nasa.gov/mission_pages/station/research/news/eu_tef/#.VgageflVikp">survive</a> in outer space (though of course we haven’t identified any non-Earth-originated life – yet).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=468&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=468&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=468&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=588&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=588&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99696/original/image-20151026-18458-14e4ll.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=588&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Comparative DNA profiles of 14 people, obtained via PCR.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/15531328629">Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<h2>Genetic fingerprints</h2>
<p>But what’s amazing about the discovery of <a href="http://www.nytimes.com/2015/05/07/science/under-the-sea-a-missing-link-in-the-evolution-of-complex-cells.html?_r=0">Lokiarchaeota</a> is that no one has ever actually <em>seen</em> it. Everything we know about it is discovered by the new field of <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351745/">metagenomics</a>, which allows us to extract fragments of DNA from the environment, read the sequence information and study it with computational techniques.</p>
<p>The starting point for metagenomic research can be anything, including feces, in the case of the <a href="http://www.pnas.org/content/109/2/594.full">human microbiome</a>, or a sample of ocean sediment, in case of Lokiarcheota. Ultimately these genetic profiles are known to us only as an electronic string of 1’s and 0’s in computer memory and described to us by mathematical algorithms. </p>
<p>Such molecular and computer technologies are also how modern detectives “use DNA” to catch murderers. </p>
<p>First, we find some DNA in the environment that may be of interest to us, by fishing for it with molecular probes called <a href="http://www.nature.com/scitable/definition/primer-305">primers</a>. Then we can use the Polymerase Chain Reaction (<a href="https://youtu.be/2KoLnIwoZKU">PCR</a>) to make a huge number of copies of the DNA of interest. That allows machines to read the genetic information it contains directly into computer databases. </p>
<p>These digital databases are where biodiversity information is now stored. They’re replacing the dusty drawers of natural history museums, filled with corpses of specimens collected over the centuries.</p>
<h2>Is the concept of species itself endangered?</h2>
<p>Anyone who watches crime shows knows well the detective value of such databases in identifying criminals by allowing the comparison of enormous quantities of information.</p>
<p>It’s the same for biodiversity study. For example, a <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1000564">new species of elephant</a> was recently discovered using these techniques to analyze and compare the DNA of living elephants and even DNA extracted from museum specimens of the extinct mammoth. We now know that African elephants that live in the forests are as genetically different from those on the savanna as humans are from chimpanzees. </p>
<p><em>Eschericia coli</em> – perhaps the most famous microbial species of all – provides an example of how the idea of “species” itself is on its way to extinction. Look at one genome of <em>E coli</em> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974192/">you will find</a> that more than half the genes may or may not be found in some other <em>E coli</em>. Looking at the sequences, many isolates of the food-poisoning bacteria <em>Shigella</em> look more like <em>E coli</em> and vice versa.</p>
<p>So these days questions of molecular diversity arise, not questions about species number. How and why does gene content change, not just in microbes like <em>E coli</em> but in us as well: we have about 20,000 genes and have recently discovered that at least 200 of them may be <a href="http://www.independent.co.uk/news/science/human-genome-study-reveals-certain-genes-are-less-essential-than-previously-thought-a6674001.html">dispensable</a>, given that perfectly healthy people do not have them at all.</p>
<p>How promiscuous is life with its genetic information? We have seen <a href="http://www.the-scientist.com/?articles.view/articleNo/23469/title/Virus-may-aid-photosynthesis/">viruses borrowing cassettes </a> of photosynthetic information from their hosts. How does our genetic diversity interact with that of the rich ecosystem living in our <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667473/">gut</a> with its impacts on human health? One entire domain of life, the Archaea, has not a single example of a “species” causing disease in <em>anything</em> – <a href="http://blogs.scientificamerican.com/artful-amoeba/archaea-are-more-wonderful-than-you-know/">why</a>? </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99695/original/image-20151026-18458-1t808dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Not a butterfly net in sight in the modern biodiversity lab.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/qiagen/7690578078">QIAGEN</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<h2>What do we gain by studying biodiversity?</h2>
<p>We study biodiversity for two reasons that go hand in hand. First, of course, we value scientific knowledge for its own sake. </p>
<p>Remarkable discoveries in pure knowledge abound. We now know that an organism discovered so recently that most people have still never heard of it, <a href="http://www.pbs.org/newshour/updates/tiny-ocean-organism-brought-earth-life/">Prochlorococcus</a>, produces 20% of the world’s oxygen. That’s one in every five breaths you take! The research spotlight has recently focused on the <a href="https://theconversation.com/us/topics/gut-bacteria">biodiversity of your gut</a>, an ecosystem at least as complex and interesting as the tropical forest.</p>
<p>Secondly, this knowledge lets us lay claim to the natural world and exploit our knowledge of it. The European study of biodiversity has long had <a href="http://www.britishempire.co.uk/science/agriculture/plantimperialism.htm">imperial</a> motivations. Jefferson commissioned the Lewis and Clark expedition to further America’s Manifest Destiny but ensured it had a pure <a href="http://www.nps.gov/nr/travel/lewisandclark/encounters.htm">biodiversity research</a> component as well: <a href="http://fwp.mt.gov/mtoutdoors/HTML/articles/2006/lcbotany.htm">Jefferson’s interest</a> in botany and its applications was well-known. </p>
<p>People have a long history of exploiting the knowledge that comes from basic research. For instance, the molecular detective work that identified <a href="http://www.nytimes.com/2008/10/07/health/07nobel.html?oref=slogin&_r=0">HIV as the cause of AIDS</a> has enabled us to turn a dreadful fatal disease into a chronic, manageable affliction. The commercial potential in Archaea is famous and almost unbelievable, as <a href="http://www.nature.com/scitable/blog/microbe-matters/a_microbepowered_battery">batteries</a> or <a href="http://rsif.royalsocietypublishing.org/content/10/84/20130197#sec-4">optical computer memory</a>, for example.</p>
<p>New forms of life continue to turn up. Most viruses, like HIV and influenza, have about 10 genes. Giant viruses, only discovered in the last decade, have over 1,000, the same order of magnitude as Prochlorococcus. The huge <a href="http://news.nationalgeographic.com/news/2013/07/130718-viruses-pandoraviruses-science-biology-evolution/">Pandoravirus</a> is full of genes that are unlike anything known – hence the name – prompting the question whether they’re a fourth domain of life.</p>
<p>As the hunt for biodiversity gets ever more technical and specific, get ready for a continuing stream of radical new discoveries. As Hamlet said: “There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy.”</p><img src="https://counter.theconversation.com/content/48069/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sean Nee does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Forget the pith helmet and butterfly net. Discovering biodiversity now is much more about metagenomics and the 0’s and 1’s of digital databases.Sean Nee, Research Professor of Ecosystem Science and Management, Penn StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/162092013-07-23T04:59:26Z2013-07-23T04:59:26ZHow a 200-year-old mummy revealed secrets of TB<figure><img src="https://images.theconversation.com/files/27845/original/txkbcjg7-1374520543.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Barbara, 14-year-old sister of Terézia Hausmann, who was found in the same crypt.</span> <span class="attribution"><span class="source">Ildiko Pap </span></span></figcaption></figure><p>In 1994, a crypt containing 242 bodies was discovered in Vác, Hungary. Many of the bodies were naturally mummified, including the remains of a woman, Terézia Hausmann, who died apparently from <a href="http://www.who.int/topics/tuberculosis/en/">tuberculosis</a>. Because of the natural preservation of these remains, we could extract and type the DNA from the bacterium, <em>Mycobacterium tuberculosis</em>, that had infected her. This has revealed <a href="http://discovery.ucl.ac.uk/1308095/">important information about these bacteria</a> that infected people 200 years ago. </p>
<p>The mummies, when carefully analysed, reveal key data about the lineages of <em>M. tuberculosis</em> that infected people then. It is important we understand how <em>M. tuberculosis</em> has changed over time as new strains are developing that are more dangerous. Some are spread more easily from person to person, and others are resistant to most, if not all antibiotics. </p>
<p>Today <a href="http://www.who.int/mediacentre/factsheets/fs104/en/index.html">two-thirds of the global human population</a> is infected with <em>M. tuberculosis</em> but only 10% will ever develop active tuberculosis (TB). This is a sign that this disease has co-existed with humans for thousands of years. Such co-existence, we believe, has led to evolution of humans and <em>M. tuberculosis</em>, so that different human populations from around the world are likely to have a particular strain or lineage of <em>M. tuberculosis</em>.</p>
<p>These mummified bodies found in the town of Vác were in a sealed crypt in an 18th century church, that was found to be full of coffins. Most bodies were totally or partially naturally mummified, because of local environmental conditions. Church and civic archives made it possible to identify many individuals and to discover their family relationships, date of death, age at death, occupation, and sometimes even a record of symptoms before death.</p>
<p>Analysis of tissue and bone samples confirmed that over <a href="http://discovery.ucl.ac.uk/628/">60% of the mummies had TB</a> and in some cases the DNA was extremely well preserved. TB then was widespread in Europe as it is linked to the population density and at that time people were moving into towns and cities. </p>
<p>TB is mainly a lung infection, so the human population density is important because this increases the transmission of bacteria from person to person via their breath. With data from Hungarian archive, a correlation between transmission rates based on population density could be determined too. Also, at this time in history there was no effective treatment, so people only survived if they had good natural resistance. </p>
<p>Scientists can estimate the rate of change in <em>M. tuberculosis</em> over time, based on the chances of genetic mutations and rearrangement occurring in the bacterial genome. However, palaeomicrobiology – the study of ancient microbes via their DNA and other such markers – enables researchers to examine historical and archaeological material directly. This provides calibration in real time of when particular genetic changes occurred.</p>
<p>Although DNA can be damaged by reaction with oxygen, water and enzymes produced during the natural decay process after death, sometimes the local conditions enable both human remains and their infecting bacteria to be very well preserved, as was seen in the Hungarian mummies. </p>
<p>Whole Genome Sequencing, or metagenomics, is a technique that examines all DNA in a sample. DNA fragments are tagged, sequenced and analysed using specialist software. Our work published this week in the <a href="http://dx.doi.org/10.1056/NEJMc1302295">New England Journal of Medicine</a> was a metagenomic study based on lung tissue of Hausmann, who died on 25 December 1797, aged 28 years. </p>
<p>Our analysis reveals that the bacterial DNA was much better preserved than the human DNA. At first this may seem surprising, as the TB bacteria would not be evenly distributed in its human host, and during life its DNA would be very much in the minority. However, <em>M. tuberculosis</em> has a very tough cell wall. It is rich in lipids and we know that it can persist in the bones of its host for thousands of years. In comparison, human DNA readily degrades as it has no such resistant cell wall to protect it. </p>
<p>Hausmann was infected with two strains of <em>M. tuberculosis</em>. Both strains resembled the Haarlem lineage of <em>M. tuberculosis</em>, specifically, a clone of the lineage that appeared to spread preferentially in modern-day Germany.</p>
<p>The importance of this work is that it enables us to compare strains of <em>M. tuberculosis</em> from 200 years ago with those of today. In the 18th century there was no effective treatment for TB as it was in the pre-antibiotic era. However, the population in Vác included some individuals who had localised evidence of infection but who lived to a considerable age. The comparison of ancient DNA of both <em>M. tuberculosis</em> and also the human population, who had either active or latent infections, may shed light on genetic factors involved in how TB spreads or how it develops resistance.</p><img src="https://counter.theconversation.com/content/16209/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helen Donoghue does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>In 1994, a crypt containing 242 bodies was discovered in Vác, Hungary. Many of the bodies were naturally mummified, including the remains of a woman, Terézia Hausmann, who died apparently from tuberculosis…Helen Donoghue, Honorary Senior Lecturer, UCLLicensed as Creative Commons – attribution, no derivatives.