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Category Archives: Genome
Eerily on the mark, a gene detective’s coronavirus findings raise hope and fear in equal measure – Economic Times
Posted: March 27, 2020 at 8:46 am
By Robert Langreth
In a few short weeks, Seattle-based biologist Trevor Bedford, 38, has emerged as one of the most famous epidemiologists in the world. His frequent tweets are seized upon by many of the globes top scientists and health policy makers. So far he has more than 170,000 Twitter followers, with thousands more joining every day.
But, unlike traditional epidemiologists, this disease detective working from his lab at the Fred Hutchinson Cancer Research Center, doesn't do field work to track down Covid-19 patients contacts. Instead, Bedford and a handful of colleagues spanning the globe from Seattle to Basel, Switzerland, and Wanaka, New Zealand analyse hundreds of virus genomes from patient samples to trace where outbreaks came from, how they spread from one corner of the Earth to the next and, most important, detecting early signs of infection clusters.
The teams analytic approach relies on tracking how viruses mutate over time as they spread from person to person. In the case of the coronavirus, whose RNA consists of about 30,000 genetic bases or letters, it mutates about twice a month. These minor mutations tend not to change the potency of the virus. But they provide clues for genetic detectives to chart how they shift subtly over time, allowing them to create sprawling family trees, or phylogenies, that show how the coronavirus has spread from one part of the world or country to the next.
So far Bedfords findings, which he summarizes promptly on Twitter, have been eerily on the mark, fueling his sudden celebrity status among fellow scientists and public health experts.
Trevor Bedford offered some of the most careful analysis of this pandemic from the very beginning, former Food and Drug Administration Commissioner Scott Gottlieb wrote in a March 14 tweet. His estimates on the emerging epidemic in U.S. should be taken very seriously.
Three weeks ago, when U.S. authorities still thought they might have the coronavirus somewhat under control, Bedford was among the first to argue that it had already been circulating undetected in the Seattle area for weeks. Virus-genome analyses suggested to Bedford that the very first patient in Washington in January, a 35-year-old man who had recently visited Wuhan, China, somehow infected someone else, allowing the disease to spread undetected for all that time around the Seattle area.
There are some enormous implications here, Bedford said in a nine-part Twitter thread on February 29 that has since been retweeted thousands of times. I believe we're facing an already substantial outbreak in Washington State that was not detected until now due to narrow case definition requiring direct travel to China.
This genome work differs markedly from traditional epidemiology that focuses heavily on identifying infected patients and tracking all their contacts. Instead of talking to people about who they have been in contact with and shoe-leather epidemiology, we use the genetics of pathogens to see how they are spreading and how they are transmitting around the world, says Emma Hodcroft, a molecular epidemiologist at the University of Basel who works closely with Bedford.
Genome sequencing has gradually become a more and more powerful tool over for tracking diseases. In the 2014 Ebola outbreak in West Africa, genome analyses helped trace the origin to a transmission strain that had been missed, allowing the disease to spread quietly for months in Sierra Leone. But that work took months to perform. Recently, genome sequencing has become a standard tool for tracing the source of bacteria-tainted produce.
Twitter has also become a crucial tool. Bedford says he has long written Twitter threads to accompany his scientific papers. But the coronavirus has moved so swiftly he hasn't had time for scientific papers lately. Once the first genome came out in January, I basically started doing science over Twitter, he says.
Along with the science sometimes comes an inspirational call to arms. We can bring this epidemic under control, he wrote in a thread that was retweeted 5,000 times. This is the Apollo program of our times. Let's get to it.
In his 19-part March 18 Twitter thread, Bedford offers way to do just that. One path out of the crisis, he says, could be via a massive effort to roll out in-home testing kits and drive-through sites to spot cases early on and then combine those with cellphone location data to trace all the previous movements of those who test positive.
He says he finds his newfound Twitter fame a bit bewildering. This has been very, very surreal, says Bedford, who's been working 16-hour days since the outbreak started. I am getting all this attention for doing this, and meanwhile everyone else's lives are being upended in terrible ways.
One of his key collaborators, Richard Neher, is a computational biologist at the University of Basel. Neher says the two scientists hit upon the idea of tracking virus evolution in real time using an interactive website after meeting at a conference at the University of California Santa Barbara in 2014. Their original idea was focused on influenza evolution, with the goal of helping vaccine makers predict which strains are likely to spread around the world in the next flu season. But over time their website, Nextstrain.org, evolved to include data from multiple outbreaks including Zika, Enterovirus D68 and Ebola.
When the coronavirus hit, Bedford and Neher had customized software ready to roll for rapidly analyzing hundreds of virus genomes. We hit the ground running here because all of this basic infrastructure was in place, Neher says.
Since then, Nextstrain has become a 24/7 operation, staffed with researchers at Bedfords and Nehers labs in Seattle and Basel, along with another scientist in New Zealand. With global coverage, someone is always on call to start analyzing data as soon as a new viral genome is released to gisaid.org, a website where scientists are posting the information. It takes about 20 to 30 minutes to analyze a new viral genome, allowing the website to be updated frequently.
Bedford sees his work as expanding, not replacing, the utility of existing virus-tracing methods, providing new data streams to complement traditional epidemiology. And while the evidence he gathers stops short of proving a chain of transmission, my suspicion is almost everything we have seen in the Seattle area is part of the same transmission chain, he says.
He started analyzing coronavirus genomes from China as soon as they began to flow into public databases on January 10th. At the time, health authorities were claiming that the virus had limited ability to spread between people. But Bedford found something alarming: The viral genomes were too similar to derive from viruses from different animals infecting people on multiple occasions. Instead, the genome data suggested that someone had acquired it from a single infected animal around early December and it had been spreading from person to person ever since.
This genomic data represented one of the first and strongest indications of sustained epidemic spread, Bedford said in a Jan. 31 blog post. I spent the week of Jan 20 alerting every public health official I know.
Bedford and Neher are limited by the amount of genome data that is available. So far almost 1,000 patients have had their viral genomes analyzed, out of more than 350,000 people who have been infected. There are few virus genome sequences from New York, which has surpassed Washington as the hardest-hit state in the country. Overwhelmed testing centers often don't have manpower to spare to do genome analysis when so many people are having trouble getting test results.
Even so, a basic picture is emerging: Most of the coronavirus clusters now spiraling out of control in Europe and the United States likely date back to community spread that had been quietly percolating for many weeks.
We were thinking , Neher says, it was all in China and China's problem, but that was not true."
Researchers Look At How The Coronavirus Is Mutating And Possible Consequences : Goats and Soda – NPR
Posted: at 8:46 am
A colorized image of cells from a patient infected with the coronavirus SARS-CoV-2. The virus particles are colored pink. The image was captured from a scanning electron micrograph. NIAID/Flickr hide caption
A colorized image of cells from a patient infected with the coronavirus SARS-CoV-2. The virus particles are colored pink. The image was captured from a scanning electron micrograph.
As the new coronavirus continues to spread around the globe, researchers say the virus is changing its genetic makeup slightly. But does that mean it is becoming more dangerous to humans? And what would the impact be on any future vaccines?
"In the literal sense of 'is it changing genetically,' the answer is absolutely yes," says Marc Lipsitch, an infectious disease epidemiologist at Harvard University. "What is in question is whether there's been any change that's important to the course of disease or the transmissibility or other things that we as humans care about."
So far, "there is no credible evidence of a change in the biology of the virus either for better or for worse," says Lipsitch.
Coronaviruses like all viruses change small parts of their genetic code all the time.
"Viruses mutate naturally as part of their life cycle," says Ewan Harrison, scientific project manager for the COVID-19 Genomics UK Consortium, a new project that tracks the virus in the United Kingdom.
Like flu and measles, the coronavirus is an RNA virus. It's a microscopic package of genetic instructions bundled in a protein shell. When a virus infects a person, the string of genetic instructions enables the virus to spread by telling it how to replicate once it enters a cell. The virus makes copies of itself and pushes them out to other cells in the body. Infectious doses of the virus can be coughed out in droplets and inhaled by others.
Inevitably, viruses "make mistakes in their genomes" as they copy themselves, says Harrison. Those changes can accumulate and carry over to future copies of the virus. Researchers are using these small, cumulative changes to trace the pathway of the virus through groups of people.
So far, researchers who are tracking the genetic changes in SARS-CoV-2 the official name for the coronavirus say it seems relatively stable. It acquires about two mutations a month during this process of spread, Harrison says about one-third to one-half the rate of the flu.
Coronaviruses differ from flu viruses in another key way that reduces the number of mutations. They proofread their own genomes when they copy themselves, cutting out things that don't seem right. "They maintain this ability to keep their genome pretty much intact," says Vineet Menachery, a virologist at the University of Texas Medical Branch. "The mutations that they incorporate are relatively rare."
This added proofreading function means that coronaviruses are also one of the largest RNA viruses. They're about 30,000 nucleotides long double the size of flu viruses. But at 125 nanometers wide, they're still microscopic; 800 of them could fit in the width of a human hair.
Nonetheless, their relatively larger size means "they have a lot more tools in their tool belt" compared with other RNA viruses, says Menachery in other words, more capability of fighting off a host's immune system and making copies of themselves.
Researchers are on alert for changes that might affect how the coronavirus behaves in humans. For instance, if the coronavirus developed ways to block parts of our immune system, it could hide out in our bodies and establish itself better. If it evolved to bind more strongly to human cells, it could enter them more efficiently and replicate more quickly.
But it's not as if the coronavirus needs to become more potent to survive and thrive. It's already replicating itself around the world very successfully, says Justin Bahl, an evolutionary biologist at the University of Georgia. "The viruses themselves are not actually under much pressure to change."
Selective pressures could come from introducing treatments and vaccines that are effective against a narrow group of coronavirus strains. If that happens, strains that aren't targeted by these measures would likely proliferate.
The small genetic changes that researchers have observed so far don't appear to be changing the function of the virus. "I don't think we're going to see major new traits, but I do think that we're going to see different variants emerge in the population," says Bahl.
And that slower rate of change is potentially good news for treatments and vaccines. Researchers think that once a person gains immunity against SARS-CoV-2, either by recovering from an infection or by getting a future vaccine, they will likely be protected against the strains in circulation for "years rather than months," predicts Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center, in an assessment shared on Twitter.
Projects such as the COVID-19 Genomics UK Consortium will use these genetic drifts to track the path of the virus and figure out if there are hospitals or community hubs that are hot spots for contagion, according to Harrison. This will give public health officials a sense of where and how the virus is being transmitted now.
Will the coronavirus surge when schools reopen? Will new strains emerge that develop resistance to drugs or vaccines that are introduced? To answer such questions, Harrison says, the long-term plan is to track the virus in real time and see how it changes as it spreads.
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Researchers Look At How The Coronavirus Is Mutating And Possible Consequences : Goats and Soda - NPR
IntegraGen Announces Leading U.S. Cancer Center to Use MERCURY Cloud-based Tool for Oncology Sequencing Data Interpretation and Reporting – Yahoo…
Posted: at 8:46 am
IntegraGen (Paris:ALINT), a company specializing in the transformation of data from biological samples into genomic information and diagnostic tools for oncology, today announced Dana-Farber Cancer Institute will utilize the companys MERCURY cloud-based software as part of their analysis and reporting process for sequencing data obtained from tumors of cancer patients. Dana-Farber plans to utilize MERCURY to assist in the analysis of sequencing data obtained from small and large targeted gene sequencing panels as well as data derived from whole exome and genome sequencing.
"Genomic profiling of tumors can assist in the identification of pathogenic molecular alterations which drive a patients cancer and enable the implementation of precision medicine-based approaches to treatment," stated Annette S. Kim M.D., Ph.D., Co-Director of the Dana-Farber Cancer Institutes new Interpretive Genomics Program within the Department of Oncologic Pathology. The program is Co-Directed by Keith L. Ligon, MD PhD, Director of the Dana-Farber Center for Patient Derived Models. "MERCURY provides us with a tool to rapidly interpret large scale and complex genomic sequencing data with the added ability of customization to meet our specific analysis and reporting needs to support clinical research and clinical trials."
"IntegraGen is excited about Dana-Fabers decision to utilize MERCURY and look forward to interacting with another world leader in cancer care related to the utilization of our cloud-based bioinformatic tools," said Larry Yost, General Manager of IntegraGen, Inc. "We are convinced that the use of MERCURY will aid in the better understanding of the etiology of a patients cancer and assist with the realization of the benefits of precision medicine by transforming large-scale sequencing data into actionable results. We are also looking forward to continuing the development and expansion of our genomic interpretation software tools in North America."
MERCURY is a user-friendly genomic interpretation tool for oncology designed to assist pathologists and oncologists to rapidly transform raw data obtained via high-throughput sequencing into a clinical molecular report for clinical and research use. The cloud-based tool minimizes the complexity, time and cost associated with the clinical interpretation and identification of variants that may be of interest in the therapeutic management of patients. MERCURY utilizes the Google Cloud technology to ensure a secure environment for data analysis and storage which is compliant with the latest information security requirements.
IntegraGen is a company specializing in the analysis of the human genome and performs adaptive and quickly interpretable analyses for academic and private laboratories. For the management of cancers, which are characterized by a genetic disruption of cells, IntegraGen provides researchers and doctors with universal and individualized therapeutic guidance tools allowing them to adapt the treatment to the patient's genetic profile.
IntegraGen has forty-six employees and generated revenue of 8.3 million in 2019. Based in the Gnopole d'Evry, IntegraGen is also located in the United States in Cambridge, MA. IntegraGen is listed on Euronext Growth in Paris (ISIN: FR0010908723 - Mnemo: ALINT - Eligible PEA-PME).
For more information, visit http://www.integragen.com
View source version on businesswire.com: https://www.businesswire.com/news/home/20200326005546/en/
Contacts IntegraGen Bernard COURTIEUPresident and CEO
Laurence RIOT LAMOTTEChief Financial Officercontact@integragen.com Tel: +33 (0)1 60 91 09 00
NewCap Investor and Media RelationsLouis-Victor DELOUVRIERintegragen@newcap.eu Tel: +33 (0)1 44 71 98 53
Posted: at 8:46 am
The UK government has backed their leading clinicians and scientists this week with new resources to map how COVID-19 spreads and evolves using whole-genome sequencing. Through a 20 million investment, the consortium will look for breakthroughs that help the UK respond to this and future pandemics, and save lives.
The COVID-19 Genomics UK Consortium COG-UK comprised of the NHS, Public Health Agencies and academic institutions including the University of Birmingham will deliver large scale, rapid sequencing of the cause of the disease and share intelligence with hospitals, regional NHS centres and the Government.
Samples from patients with confirmed cases of COVID-19 will be sent to a network of sequencing centres which currently includes Birmingham, Belfast, Cambridge, Cardiff, Edinburgh, Exeter, Glasgow, Liverpool, London, Norwich, Nottingham, Oxford and Sheffield.The Wellcome Trust Sanger Institutewill provide large-scale sequencing capacity and additional support.
The University of Birmingham, led byNick Loman, Professor of Microbial Genomics and Bioinformatics in theInstitute of Microbiology and Infection, have deployed a real-time genome sequencing facility established at the University capable of sequencing genomes of the virus causing COVID-19 from patients in the West Midlands in less than 24 hours.
Professor Loman says: This is a remarkable collaboration which brings together Birmingham and the UKs incredible depth of expertise and knowledge in viral sequencing and genomics. An open and distributed model of sequencing involving both academia, the NHS and our public health bodies is the right way to ensure results are delivered quickly to decision-makers. We are now well positioned to return deep insights into understanding the rapidly-accelerating pandemic of COVID-19, easily the most pressing infectious disease emergency we have faced in two generations in the UK.
The governments investment is well-timed to accelerate the pace of viral genome sequence production and ensure this information is openly available to epidemiologists and virologists worldwide. This will provide an unprecedented real-time view of COVID-19 virus evolution.
Understanding viral evolution is important for understanding how the virus is spreading in local, national and international settings. It provides valuable epidemiological information revealing the chains of transmission that must be stopped in order to stop this outbreak.
We also stand to observe how the virus adapts to a human host over time, and how human interventions including drug treatments and eventually vaccines, exert pressure on the virus.
The consortium benefits from two major initiatives in which the University of Birmingham has played a pivotal role: ARTIC and CLIMB.The CLIMB project,which recently secured funding for a further five years with the CLIMB-BIG-DATA project, will provide the data analysis pipelines, computing and storage capacity required to analyse the large genome datasets produced by the consortium, as well as facilitating national and international research capabilities.
The ARTIC project,funded by a Wellcome Trust Collaborative Award, is a collaborative project to put genomics at the heart of outbreak response. Dr Josh Quick, a UKRI Future Leaders Fellow in the Institute of Microbiology and Infection rapidly developed a method for sequencing coronavirus, released to researchers back in January, and which has already been widely adopted across the world. This method builds on work previously successfully used to trace epidemics of Ebola virus and Zika virus.
Dr Quick says: Based on previous experiences with Ebola and Zika virus we were able to rapidly develop an approach to sequencing the COVID-19 virus rapidly using a targeted method. The importance of this method is that it works well even when only miniscule amounts of virus are present in the sample, something we commonly see. It has been used to generate the first genomes from countries including Brazil, Scotland, Wales and Northern Ireland with nanopore sequencing and we have helped over 50 groups in over 20 countries establish genome sequencing capabilities in their own labs.
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University of Birmingham joins COVID-19 Genomics UK Consortium - insideHPC
Posted: March 24, 2020 at 5:54 am
As Silicon Valley is gearing up to fight against the novel coronavirus, NVIDIA is putting its GPU technology to use by enabling researchers and gamers to join the on-going efforts.
GPUs are not only meant to enhance the gaming experience through fast graphics or accelerating the training and inference of machine learning models. They also play a crucial role in assisting the scientific community involved in researching genome analysis and sequencing.
To fight the growing threat of novel coronavirus, NVIDIA is making its platform, Parabricks, free for 90 days to any researcher working on sequencing the novel coronavirus and the genomes of people afflicted with COVID-19.
Genome analysis is a computationally intensive effort that needs a high performance computing environment powered by CPUs and GPUs. Sequencing platforms such as DNBSEQ-T7 from MGI generate as much as 6 TerraBytes of data every day, which is analyzed by scientists performing whole genome sequencing. According to NVIDIA, these systems will generate about 20 ExaBytes of data by 2025 more than Twitter, YouTube and astronomy combined. Interestingly, it would take all the CPUs in every cloud and more than 200 days to run genome analysis.
Parabricks, an Ann Arbor, Michigan-based startup, built a platform based on GPU to speed up the process of analyzing whole genomes all 3 billion base pairs in human chromosomes from days to under an hour.
As platforms like DNBSEQ-T7 generate more data, analysis has becomes a major bottleneck in both time and cost perspectives. Parabricks solution addresses both of these barriers to accelerate the genomic analysis.
Parabricks platform is powered by NVIDIA CUDA-X and benefits from CUDA, cuDNN and TensorRT inference software and runs on NVIDIA entire computing platform from NVIDIA T4 to DGX to cloud GPU instances.
Earlier this year, NVIDIA acquired Parabricks with a goal to release the companion technology that accelerates single-cell and RNA analysis.
The Parabricks acquisition helped NVIDIA to officially offer genome sequencing and analysis on its HPC platform.
By making Parabricks accessible to the research community, NVIDIA aims to dramatically reduce the time for variant calling on a whole human genome from days to less than an hour on a single server.
Since Parabricks is available as a part of NVIDIA GPU Cloud (NGC), it is expected to run on major cloud platforms and NVIDIAs own appliances including DGX-1. Researchers with access to NVIDIA GPUs can fill out a form to request access to Parabricks.
Apart from offering Parabricks free for 90 days, NVIDIA is also encouraging gamers to participate in the Folding@Home project, a distributed computing project for disease research that simulates protein folding, computational drug design and other types of molecular dynamics.
Folding@home is a collaborative project focused on disease research. The problems they deal with rely on many calculations that can be effectively offloaded to idle PCs running in homes and offices for globally distributed processing. The project is managed by Washington University in St. Louis School of Medicine.
NVIDIA is joining Intel and AMD in an effort to utilize unused GPU computing power on PCs and gaming machines to fight against COVID-19.
NVIDIA is putting its best technology to use in fighting COVID-19 through the 90 day free trial of Parabricks and by participating in the Folding@Home project.
Covid-19: How unprecedented data sharing has led to faster-than-ever outbreak research – Horizon magazine
Posted: at 5:54 am
When the new coronavirus (formally known as SARS-CoV-2) was identified in China in January, scientists around the world were ready to respond. The viruss entire genetic makeup, or genome, was published online within days. By comparison, during the SARS coronavirus outbreak in 2003, this took almost three months, after the disease was originally blamed on chlamydia.
Advances in the technology have brought down the cost of gene sequencing significantly and the machines are now small enough to fit in the palm of your hand. This has made it easier for a large number of samples to be sequenced around the world.
You can see from the sequences how the virus spreads, the speed at which it's spreading and estimate the number of people that are infected. As we get more and more sequences, the more and more accurate the numbers are, said Professor Anne-Mieke Vandamme from KU Leuven, Belgium.
Next-generation sequencing, or NGS, can generate enormous amounts of data, and the challenge becomes finding ways to analyse it properly.
In 2015, Prof. Vandamme led a project called VIROGENESISto develop new tools to help analyse and interpret the data that comes from sequencing, particularly for laboratories that were not used to dealing with sophisticated genetic analysis.
When we were doing the project, there were only mainly research labs that had NGS. Now everyone has NGS, she said.
One of the tools developed, called Genome Detective, can take the raw data from the sequencing machine, filter out results from non-viruses, piece together the genome and use that to identify the virus. It does not rely on any prior guesses or hypotheses, so it can even identify viruses that have not been seen before. This was used to confirm the first case of COVID-19 in Belgium, identifying it as a SARS-related coronavirus.
You can see from the sequences how the virus spreads, the speed at which it's spreading and estimate the number of people that are infected.
Professor Anne-Mieke Vandamme, KU Leuven, Belgium
The power of gene sequencing comes from comparing the results across different cases. Prof. Vandamme says that it has been fantastic to see the level of collaboration internationally: There is a lot more online sharing of data and sequences ... compared to the past because we have a lot more online sharing tools available.
One of these tools is NextStrain, an online resource that uses genome data to monitor the evolution of disease-causing organisms such as viruses in real time. It has tracked several outbreaks including Zika, Ebola and Dengue and has even been used to inform World Health Organization policy on seasonal flu.
Research papers typically take months to be published an aeon in the current race to tackle the pandemic. The need to share information quickly has encouraged greater sharing of preprints, drafts of papers that have not yet been through peer review.
The push towards open science, open data and preprinting has really changed the way we experience the scientific discourse in this outbreak compared to previous ones, said Professor Richard Neher, from the University of Basel, Switzerland, who leads the NextStrain project.
NextStrain already has over 700 genomes of the new coronavirus, which it can use to trace the outbreak by detecting new mutations in the virus. The mutations do not necessarily affect how the virus behaves, but they can act as a genetic signature to link cases that are related. Like tracing your ancestry through a DNA test, a virus sequenced in Madrid, for instance, could have mutations that suggest it originated from an outbreak in Italy.
In the current pandemic, it gives us a lower bound on how often the virus has been introduced to a specific location, Prof. Neher said.
NextStrain publishes a weekly situation report that analyses these trends. The team was able to estimate that the outbreak in Iran may have been introduced by a single person, whereas at least four different introductions were responsible for the outbreak in the UK, as of 13 March.
(Sequencing cases) will become even more important because as we start cracking down on (the pandemic), which we hopefully will achieve, it will tell us how many transmission chains are still circulating and whether the virus is being transported from one region to another, said Prof. Neher.
He believes that, as the virus continues to spread, it will accumulate more genetic diversity and it will give us more information on how the virus is being transmitted.
Despite the genetic blueprint of the new coronavirus being readily available, it still does not tell us very much about how it differs from other coronaviruses. Much of what we know has come from seeing how it has spread through the population. It is now clear how different it is to previous coronavirus outbreaks, such as SARS and MERS.
They were certainly much less easy to transmit, and also had a very different presentation in that only a few people were asymptomatic. One of the many challenges that we are facing here is that people that have only very mild symptoms have been substantial in transmitting this virus,' said Prof. Neher.
That is much harder to control because you have to convince somebody who is basically healthy to distance themselves from others.
Yet, it is not clear why that is the case. The traits of the virus, such as its infectiousness and severity, are driven by its proteins that are responsible for invading our cells and replicating the viral genome.
Sequencing a genome these days is pretty fast, but for proteins its different, said Dr Charlotte Uetrecht, from the Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Germany. She studies coronavirus proteins through a project calledSPOCkS MS.
My lab is producing the proteins (of the new coronavirus) right now. So we want to see whether they behave the same (as other coronaviruses). We usually need to produce the proteins and purify them to a certain extent so we can look at them. So it's a lot more laborious than sequencing.
Even small changes to the viral proteins can significantly influence how they interact with each other. Dr Uetrecht studies these fleeting associations, which are crucial for the virus to replicate.
We know a bit about how that looks, but we don't really understand which of the proteins need to associate for a new genome to be produced, she said.
Although understanding these processes could provide new targets for antiviral drugs, Dr Uetrecht says that historically there has been little interest in studying coronaviruses as they have had little relative impact until now.
The case numbers were low for SARS and MERS andinterest fell after the outbreaks, she says. 'The common-cold-causing coronaviruses were not (considered) dangerous.'
There was not much research into coronaviruses at all, until SARS. I know a few people who have been working on coronaviruses since the '90s, and they were not very well regarded they had a hard time getting funding. It was considered a boring, irrelevant virus.
Now, it is very interesting again.
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Posted: at 5:54 am
Newswise Inside the molecular diagnostics laboratory at Johns Hopkins Hospital in Baltimore, while health care workers and hospital staff work tirelessly to process patient tests to detect the virus causing the COVID-19 pandemic, two biologists from the Johns Hopkins Applied Physics Laboratory (APL) are working alongside them.
Peter Thielen and Tom Mehoke, members of APLs Research and Exploratory Development Department, are waiting for the positive tests. Certainly, positive tests are no cause for celebration; but for Thielen and Mehoke, they are an invaluable sample and a key to learning more about the rapidly spreading virus.
With software and molecular biology approaches developed in part at APL in Laurel, Maryland, Thielen and Mehoke are using hand-held DNA sequencers to conduct immediate on-site sequencing of the SARS-CoV-2 genome the virus that causes COVID-19.
This information allows us to track the evolution of the virus, Thielen said. It gives us a sense of where the new cases coming into Baltimore couldve originated, and insight into how long transmission may have occurred undetected. There are a lot of things we can glean from that.
Topping that list is the ability to see how quickly the virus mutates integral information for mapping its spread, as well as developing an effective vaccine. Influenza, for example, mutates constantly. Thats why its necessary to vaccinate against different strains of the flu each year.
The virus causing COVID-19, Thielen said, does not appear to be mutating as fast.
When this virus was first sequenced in China, that information was helpful in starting the process to develop a vaccine, Thielen explained. What were doing informs whether or not the virus is mutating away from that original sequence, and how quickly. Based on the mutation rate, early data indicates that this would likely be a singlevaccine rather than one that needs to be updated each year, like the flu shot.
In the near-term, the mutations inform how the virus is spreading.
With the United States continuing to ramp up testing and mitigation capabilities, the ability to understand how outbreaks are linked gives public health departments another tool for evaluation. Mutations can explain how long the virus may have gone undetected and the supposition that there are likely far more cases than diagnosed, and can advise on what measures to put in place (such as the social-distancing efforts and closings that are ongoing nationwide).
Sequencing of the virus genome is being performed by scientists all over the globe as they work to trace the source of regional outbreaks. In northern California, for example, news reports suggest that genome sequencing has linked the Bay Area outbreak to the Grand Princess cruise ship, which linked back to the virus found in Washington State, which likely came from China.
Thats the type of insight a DNA fingerprint, if you will that Thielen and Mehoke will gain as more virus genomes are sequenced from the Baltimore and Washington, D.C., regions.
As part of the Johns Hopkins Center of Excellence for Influenza Research and Surveillance, Thielen and Mehoke have sequenced the genome of influenza for years in their work at APL, and are currently transitioning similar capabilities directly to the diagnostic laboratory at Johns Hopkins Hospital.
Theyve completed analysis of the first four COVID-19 samples, with upward of 100 in the queue from the Baltimore/Washington, D.C. area, and expect many more in the coming weeks.
Operating remotely using just hand-held sequencers and laptop computers, and at the mercy of how long the tests take to return results before they can be transferred to them, Thielen and Mehokes initial method was multiday. But, at the end of last week they validated a new process that enables same-day sequencing one that can be done by the hospital staff members already administering the diagnostic tests.
Ultimately, its what theyve been preparing for.
In the last nine months, Thielen and Mehoke held two workshops with the National Institutes of Health Fogarty International Center to help train scientists from low- and middle-income countries on how to use the hand-held sequencers to do this work.
We were doing that to prepare as many researchers as we can, in the event that there would be a future pandemic, Thielen said. Its here.
The latest workshop was held last week, where they trained stateside researchers to do the same type of on-site sequencing in their own laboratories. Participants included researchers at the Walter Reed Army Institute of Research, the U.S. Naval Research Laboratory, the University of Maryland, Johns Hopkins Hospital, Johns Hopkins Bloomberg School of Public Health, Auburn University, the University of California, Berkeley, and Kansas State University. Due to recent national travel restrictions, it was held virtually.
Coronavirus: sequencing the DNA of patients screened for coronavirus might save lives – The Conversation Africa
Posted: at 5:54 am
Scientists should start sequencing the genomes of coronavirus patients. We should look for DNA differences between patients who are severely affected and those with mild symptoms. This could allow us to predict who else would be vulnerable and advise them to take precautions. We may be able to use this knowledge against the coronavirus epidemic before a vaccine is widely available.
In particular, it would be valuable to know if key DNA variations are shared by those rare people who are young and appeared to be healthy but developed severe symptoms from the coronavirus. We might then be able to predict which doctors and nurses are most at risk and remove them from the front line.
Of course, we dont yet know if accurate predictions will be possible. We dont even know if someones chances of severe symptoms from the coronavirus are affected by their genes. We could, however, answer these questions relatively cheaply and rapidly by using commonplace DNA sequencing technology.
Read more: Will warmer weather stop the spread of coronavirus?
We would need to sequence the whole genomes of coronavirus victims who need intensive care and compare them with the genomes of people who have only mild symptoms. With only a few thousand genomes from each category, we could quickly find out if there is mileage in this approach.
It may be that just one or two genes are involved. Perhaps broken genes involved in the immune system or lung cell surfaces. If so, we could quickly discover them using a method called genome-wide association study. If just a couple of broken genes make all the difference, a genetic test for coronavirus susceptibility could be simple to make, cheap and accurate.
It may be that there are thousands of genes involved. Perhaps a complex mix of genes involved in lung physiology, upper respiratory tract shape, and many other things we have never even thought of. If this is the case, working out exactly what is going on could take decades. But we need answers within weeks or months.
Here we can draw on an unexpected source of inspiration: we can use a method called genomic prediction, which has been used successfully for decades by plant and animal breeders, but is seldom used in medicine. It enables the prediction of complex traits from whole-genome sequences, even when we do not understand what any of the genes are doing.
With this approach, we do not need to spend several years working out what exactly is going on. We can construct a score from a persons whole-genome sequence that predicts their susceptibility. These scores could be obtained at the cost of (we estimate) only a few hundred pounds per person.
We took a genomic prediction approach last year for ash trees, which are dying from a fungal epidemic. By comparing the genomes of healthy versus dying trees, we discovered over 3,000 points in their genomes that contribute to susceptibility. Some of these were in genes that had known functions in host defences, but for many others, we had no idea what they did. Yet we did not need that knowledge to predict the susceptibility of other ash trees with a useful level of accuracy.
Read more: Ash dieback: one of the worst tree disease epidemics could kill 95% of UKs ash trees
We should do similar studies on humans and coronavirus. Of course, there would be more complex issues of privacy and consent than we had to deal with for ash trees. But tens of thousands of human genomes have already been sequenced around the world, so the issues around consent have been well explored. For some coronavirus patients, their genome will already be in a database.
Should we find that we can make accurate predictions, the moral and psychological challenges would be severe. Where should tests be deployed? Will people respond appropriately if they are predicted to be at risk (or not)? How would it affect health insurance? But difficult challenges are faced in every decision that we have to make in our battle against the virus.
Read more: Homemade hand sanitiser recipes that could help protect against coronavirus
Research on the genetic basis of susceptibility to the coronavirus could be done quickly and without diverting resources from research on treatments and vaccines. It might show that predictions are impossible. It might show that accurate predictions can be made. We dont know. But we need to find out. If it worked, it might protect thousands of lives before a vaccine is widely available.
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Coronavirus: sequencing the DNA of patients screened for coronavirus might save lives - The Conversation Africa
Nvidia makes its GPU-powered genome sequencing tool available free to those studying COVID-19 – Yahoo Tech
Posted: at 5:54 am
Nvidia is making its Parabricks tool available for free for 90 days (with the possibility of extension, depending on needs) to any researcher currently working on any effort to combat the ongoing novel coronavirus pandemic and spread of COVID-19. The tool is a GPU-accelerated genome analysis toolkit, which leveraged graphics processing power to take a process that previously took days, but that through its use can be accomplished in just a matter of hours.
Researchers will still need access to Nvidia GPUs for running the Parabricks genetic sequencing suite, but they won't have to pay anything for the privilege of running the software. This is a big advantage for anyone studying the new coronavirus or the patients who have contracted the illness. The GPU-maker is also providing links to different cloud-based GPU service providers to lower that barrier to entry, as well.
We've cut down drastically on genomic sequencing times in the past few years, but they still require a massive amount of computing hardware, and Parabricks, which was acquired by Nvidia late last year, has developed technology that makes it possible to sequence an entire human genome in less than an hour -- and that's using a single server, not an entire server farm.
Speed is of the essence when it comes to every aspect of the continued effort to fight the spread of the virus, and the severe respiratory illness that it can cause. One of the biggest challenges that scientists and researchers working on building potential drug therapies and vaccines for the novel coronavirus face is lack of solid, reliable information. The more sequencing that can be done to understand, identify and verify characteristics of the genetic makeup of both the virus itself and patients who contract it (both during and post-infection), the quicker everyone will be able to move on to potential treatments and immunotherapies.
The standard coronavirus test, if available, works wellbut can new diagnostics help in this pandemic? – Science Magazine
Posted: at 5:54 am
A doctor in Germany prepares a swab to test for coronavirus infection.
By Robert F. ServiceMar. 22, 2020 , 12:15 PM
As the United States races to ramp up testing for the pandemic coronavirus using technology based on the tried-and-true polymerase chain reaction (PCR), alternative approaches are beginning to roll out that could make it easier and quicker for people to learn whether they have been infected. Some methods modify the standard PCR test, which amplifies tiny bits of genetic material to enable detection, whereasothers sequence the virus directly or use the genome editor CRISPR.
Faster and cheaper tests are coming, says Evan Jones, CEO of OpGen, a rapid diagnostics company. However, he adds, developing new kinds of tests is going to take time. Some of the new tests are coming online now, but others will likely take months to validate and ready for widespread distribution.
Testing, testing, testing has been the mantra repeated again and again by World Health OrganizationDirector-General Tedros Adhanom Ghebreyesus. Diagnostic assays that identify active infections in people are vitally important for public health efforts, not just for individuals health concerns. Widespread diagnostic testing, along with isolation of the infected, contact tracing, and quarantining of those contacts, seems to have been key in South Koreas work to suppress virus spread.
In the United States, the slow rollout of coronavirus PCR tests has been widely attributed to a combination of stringent rules aimed at ensuring their reliability and a complex web of companies and health care systems responsible for developing, carrying out, and paying for tests. The Trump administration says testing is accelerating. On 16 March, at a White House press conference, U.S. Health and Human Services Assistant Secretary for Health Brett Giroir saidthe country would be able to process 1 million tests by the end of the week, and 2 million the following week. But the actual numbers arent close to that yet. According to data compiled by the COVID Tracking Project, a nonprofit collaboration of public health officials and journalists counting tests given in the United States, 191,541 PCR diagnostics have been performed as of 22 March, with 24,345 of them positive for the virus.
On 29 February, the U.S. Food and Drug Administration (FDA) posted new rules to allow for emergency use authorizations of coronavirus tests beyond the ones being made and distributed by the U.S.Centers for Disease Control and Prevention. Academic virology labs, public health departments, and companies sprang to work creating their own PCR tests. Today, some four dozen organizations have received FDA approval for their tests. Among the largest are diagnostic companies, such as Roche Molecular Systems, which received FDAs green light for its test this week. It will initially supply some 400,000 tests per week in the United States and 3 million globally, according to Alexandra Valsamakis, the companys chief medical officer. Other large companies have recently gained approval for their tests as well, including Thermo Fisher Scientific and Abbott Laboratories.
University virology labs have also leaped into the breach to help diagnose cases in their vicinity. This past week, for example, doctors at the University of Pittsburgh Medical Center (UPMC) began to use a homemade PCR test to check for infection in Allegheny county. For now, its number of tests remains small, about 100 per week. We definitely wished we had started it sooner, says Alan Wells, who heads UPMCs clinical laboratories.
PCR is the most commonly used test for diagnosing coronavirus because its highly accurate. (SeeHow does the most common coronavirus test work?) But other problems limit it. Its not getting the turnaround we need, says Steven Wolinsky, an infectious diseases physician at Northwestern University. Each test takes about 4 hours once a sample reaches a centralized testing lab, with the time split between sample preparation and the actual PCR test. With transport and queues, getting a result can take 2 to 4 days. In that time, infected people may spread the virus to many others.
Another new dimension is now being added to the coronavirus diagnostic landscape: home tests, which involve mailing a sample taken at home to a lab. Tomorrow, for example, Everlywell expects to begin toshipkits to homes and retail pharmacies. These tests will start with screening questions, either online or at a retailer, to determine whether a person is likely to have been exposed to the virus. If they are, they can receive a nasopharyngeal sampling kit by mail or can buy one from a local retailer. A person will be given detailed instructions to administer their own swab, insert it into a protective vial, and overnight mail it to one of dozens of diagnostic labs (which partnered with Everlywell and already have FDA approval) for PCR analysis.
Frank Ong, Everlywells chief medical and scientific officer, says the company expects to quickly ramp up from offering thousands of such tests per day to tens of thousands. Although each test will still likely require a 4-day wait for results, Ong says, this home sampling strategy carries major benefits: It will protect health care workers from exposure to potential infection and free up their time. We need to make sure we give them the bandwidth to take care of patients, Ong says. Other companies, including Nurx and Carbon Health, say theyre now shipping limited supplies of their own home sampling kits.
Most PCR tests for the new virus are being done with big, expensive automated machines that do many tests at once. Major hospitals or diagnostic facilities have them, but another option beginning to roll out now is smaller, less expensive devices that also do nucleic acid amplification. These could be used by smaller hospitals and even individual doctors offices.
On Friday, for example, Cepheid, which sells small PCR systems for rapidly detecting influenza viruses, tuberculosis bacteria, and other microbes, received FDA emergency use approval for a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) test cartridge that slots into the companys GenXpert system, a device the size of espresso machine that can produce a diagnostic result in as little as 45 minutes. Cepheid officials say that 23,000 such systems are in place worldwide, with 5000 in the United States. On 19 March, GenMark received FDA emergency use approval for its own coronavirus tests, which run on similar-sizemachines that use a proprietary electrochemical approach to detect target genetic material in less than 2 hours. Other companies rushing to deliver point-of-care diagnostic machines include Mesa Biotech, HiberGene, Mobidiag, and QuantuMDx.
So, too, are companies such as Oxford Nanopore and Fulgent Genetics, which instead of using PCR directly sequence any genetic material in a sample and then look for matches to, say, the new coronavirus. This high-speed gene sequencing approach could help characterize the coronavirusgenome to better understand how the virus is evolving, but it could alsobe a diagnostic in certain situations, such as remote sites without access to PCR. Oxford Nanopores handheld devices have been used in Ebola outbreaks, and the company sent many to China early in the pandemic.
The fastest way to test for the coronavirus may ultimately be offered by companies using the CRISPR genome editor, better known for adding or deleting DNA in cells. Two U.S. companies, Mammoth Biosciences and Sherlock Biosciences, say they have created CRISPR-based tests and are in the process of validating them with patient samples before seeking emergency use approval by FDA. The technique starts with a patient sample, extracts viral RNA, and uses a fast nucleic acid amplification test called loop-mediated amplification to make just enough RNA for the test to detect. Researchers then add two components of a CRISPR genome editor, a protein called CAS12 that cuts DNA or RNA and a guide RNA that slots into CAS12 and helps it search out a sequence corresponding to a piece of the coronavirus genome. If CAS12 and its guide find a match in the RNA, CAS12 binds to that matched RNA, which activates CAS12 to cut it and go on to cut any other short RNA or DNA strands in the vicinity, including copies of a strand designed to liberate color-changing molecules when CAS12 cuts them free. The upshot can be a simple color change on a test strip.
The technique excels at hunting for small snippets of genetic material, says Jennifer Doudna, a biochemist at the University of California (UC), Berkeley, a CRISPR pioneer, who is chair of Mammoth Biosciencess science advisory board.
In a preprint posted 10 March on medRxiv, researchers at Mammoth Biosciences and UCSan Franciscoreport that tests on clinical samples produced results with accuracy rates comparable to PCR in just 30 minutes. It uses a simple paperlike strip with a colored line that appears with a positive result. The company is discussing with partners manufacturing test kits that would allow rapid and cheap diagnosis of SARS-CoV-2 infection at home without requiring medical know-how, says Trevor Martin, Mammoths CEO.
It may take months to finalize the test and get regulatory approval for it, so it likely wont be ready in the crucial weeks ahead. But it could be ready if the spread of the coronavirus continues. Some predict the virus will also recede but then have a resurgence of infections in the fall. Getting results wouldnt require PCR machines operated by trained technicians, Martin says. It would be a game changer for our response to emerging diseases, Martin says.
Even as companies and academic labs are scaling up their PCR-based diagnostic efforts, hospitals and testing sites around the country report that they are facing a more immediate crunch: Many are running out of chemicals and other materials that enable the tests, such as the swabs to collect samples from patients and the reagents needed by PCR. Benjamin Pinsky, a Stanford University pathologist who developed a PCR-based diagnostic test in use in Northern California, says his lab is facing rolling shortages of different supplies, most notably the kits used to extract RNA from viral samples, before it can be loaded into PCR machines.
This has been a big challenge, Pinsky says. Weve had to be very nimble in dealing with this, constantly switching suppliers or even chemical procedures, which must be validated before they can be used on patient samples. His team has even sent pleas over Twitter to the Stanford community and regional biotech companies calling for donations of reagent assemblies, such as kits from Zymo and Qiagen. And even though donations have been pouring in, supplies are still running short, Pinsky says.
Reagent companies are trying to respond. For example, Qiagen, a major supplier of RNA extraction kits, announced Tuesday that its employees are working around the clock to increase production from 1.5 million kits per month to 6.5 million per month by the end of April and further increases later.
Pinsky, for one, says hes ready for companies to take over coronavirus testing entirely from academics such as himself. Im hopeful these companies will be able to provide the testing they have promised, Pinsky says. That remains to be seen.