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New tools enable rapid analysis of coronavirus sequences and tracking of variants

UShER allows researchers to quickly see how a new viral sequence is related to all other variants of SARS-CoV-2, crucial information for tracking transmission dynamics Credit: UC Santa Cruz Genomics Institute The COVID-19 pandemic has spurred genomic…

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UShER allows researchers to quickly see how a new viral sequence is related to all other variants of SARS-CoV-2, crucial information for tracking transmission dynamics

Credit: UC Santa Cruz Genomics Institute

The COVID-19 pandemic has spurred genomic surveillance of viruses on an unprecedented scale, as scientists around the world use genome sequencing to track the spread of new variants of the SARS-CoV-2 virus. The rapid accumulation of viral genome sequences presents new opportunities for tracing global and local transmission dynamics, but analyzing so much genomic data is challenging.

“There are now more than a million genome sequences for SARS-CoV-2. No one had anticipated that number when we started sequencing this virus,” said Russ Corbett-Detig, assistant professor of biomolecular engineering at UC Santa Cruz.

The sheer number of coronavirus genome sequences and their rapid accumulation makes it hard to place new sequences on a “family tree” showing how they are all related. But Corbett-Detig’s group at the UC Santa Cruz Genomics Institute has developed a new method that does this with unprecedented speed. Called Ultrafast Sample Placement on Existing Trees (UShER), this powerful tool is described in a paper published May 10 in Nature Genetics.

UShER identifies the relationships between a user’s newly sequenced viral genomes and all known SARS-CoV-2 virus genomes by adding them to an existing phylogenetic tree, a branching diagram like a family tree that shows how the virus has evolved in different lineages as it accumulates mutations.

“We are able to maintain a comprehensive phylogenetic tree of more than 1.2 million coronavirus sequences and update it with new sequences in real time. No other tool can handle trees of this size with a comparable efficiency,” said first author Yatish Turakhia, a postdoctoral scholar at the Genomics Institute. “This helps us keep track of all variants in circulation, including new variants that are emerging.”

This kind of sequence analysis can be used to discover new strains of the virus as they emerge and track their evolution and transmission dynamics. It can also be used to identify links between individual cases of coronavirus infection and to trace chains of transmission, an approach known as genomic contact tracing.

“The challenge is to get results soon enough to make meaningful predictions that public health agencies can use to try to control an outbreak,” said Corbett-Detig, a corresponding author of the paper. “Our method is orders of magnitude faster than anything else out there, placing new samples in tenths of a second.”

UShER and related data visualization tools are available to the research community through the UCSC SARS-CoV-2 Genome Browser, which also provides access to a wide range of data and results from ongoing scientific research on the virus, including new variants that are especially concerning.

“Our browser is the most comprehensive information resource for mutations appearing in the virus and what they mean for our battle against it,” said coauthor David Haussler, professor of biomolecular engineering and director of the Genomics Institute. “Thanks to Russ’s team, it includes the world’s most comprehensive phylogenetic tree of the different lineages of the virus, and that tree continues to grow every week, as fast as new data appear.”

Like all viruses, SARS-CoV-2 acquires mutations as it replicates and spreads. Most of these random variations in the genome sequence have no effect on the behavior of the virus, but researchers can still use them to identify different variants or strains of the virus, see how they are related, and determine if two samples are part of the same transmission chain.

Scientists have identified several important mutations that appear to make the virus more infectious. Variants of SARS-CoV-2 with these mutations are spreading more rapidly than other variants. Coauthor Angie Hinrichs, a UCSC Genome Browser engineer, used UShER to determine that one of these variants, known as B.1.1.7, entered the United States through several independent introductions. It is now the dominant strain in the United States.

Turakhia said he has begun using UShER to study a new variant that has emerged in India and appears to be spreading rapidly there. Known as B.1.617, this lineage of the virus has two mutations of potential concern to scientists. “We don’t know yet how concerning it is, but it is important to track it,” he said.

Viral genomics can reveal transmission chains not found through conventional contact tracing, Corbett-Detig said. This approach can help identify superspreader events, where one person transmitted the virus to many others, and it can also show that two cases from the same location are actually unrelated infections, not part of the same transmission chain, because the viral sequences differ too much.

“It’s an approach that is likely to be valuable moving forward, so we’re building the tools to enable people to do this in real time,” he said. “If you want to know who transmitted the virus to whom, or where in the world a new sample may have come from, you need to take the samples from your community and project them onto the known phylogenetic tree of all the other SARS-CoV-2 genome sequences, and conventional phylogenetic methods just can’t do this in a reasonable amount of time.”

That’s because conventional methods have to recalculate the entire tree every time new sequences are added, which is much too time-consuming when there are hundreds of thousands of sequences. UShER places samples onto an existing global phylogeny almost instantly, and it provides a local subtree of the added samples and their nearest neighbors so that their relationships can be visualized and examined in detail.

The researchers showed that UShER finds the right placement in 97% of cases. In the other 3%, incorrect placements are very close to the true site and still useful for contact tracing. UShER can also be used for quality control to quickly identify and remove low-quality sequences that may contain sequencing errors. The UShER results can be visualized and explored on the Nextstrain platform for interactive visualization of phylogenetic trees and maps of how the virus is spreading.

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A training module for UShER is included in the CDC COVID-19 Genomic Epidemiology Toolkit (Module 3.3, including a video, slides, and links to more resources).

In addition to Turakhia, Corbett-Detig, Hinrichs, and Haussler, the coauthors of the paper include Bryan Thornlow and Landen Gozashti at UC Santa Cruz, Nicola De Maio at the European Bioinformatics Institute, and Robert Lanfear at Australian National University, Canberra. This work was funded by the Alfred P. Sloan Foundation and the National Institutes of Health.

Media Contact
Tim Stephens
stephens@ucsc.edu

Related Journal Article

http://dx.doi.org/10.1038/s41588-021-00862-7

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COVID-19 may never go away, but practical herd immunity is within reach

It is unlikely that we will reach full herd immunity for COVID-19. However, we are likely to reach a practical kind of herd immunity through vaccination.

The level of immunity needed — either through vaccination or infection — for practical herd immunity is uncertain, but may be quite high. (Shutterstock)

When people say that we won’t reach “herd immunity” to COVID-19, they are usually referring to an ideal of “full” population immunity: when so many people are immune that, most of the time, there is no community transmission.

With full herd immunity, most people will never be exposed to the virus. Even those who are not vaccinated are protected, because an introduction is so unlikely to reach them: it will sputter out, because so many others are immune — as is the case now with diseases like polio and mumps.

The fraction of the population that needs to be immune in order for the population to have “full” herd immunity depends on the transmissibility of the virus in the population, and on the control measures in place.

It is unlikely we’ll reach full herd immunity for COVID-19.

For one thing, it appears that immunity to COVID-19 acquired either by vaccination or infection wanes over time. In addition, SARS-CoV-2 will continue to evolve. Over time, variants that can infect people with immunity (even if this only results in mild disease) will have a selective advantage, just as until now selection has mainly favoured variants with higher transmission potential.

Electron micrograph of a yellow virus particle with green spikes, against a blue background.
The B.1.1.7 variant of the SARS-CoV-2 virus. Over time, variants of concern will likely continue to emerge. NIAID, CC BY

Also, our population is a composition of different communities, workplaces and environments. In some of these, transmission risk might be high enough and/or immunity low enough to allow larger outbreaks to occur, even if overall in the population we have high vaccination and low transmission.

Finally, SARS-CoV-2 can infect other animals. This means that other animal populations may act as a “reservoir,” allowing the virus to be reintroduced to the human population.

Practical herd immunity

Nonetheless, we are likely to reach a practical kind of herd immunity through vaccination. In practical herd immunity, we can reopen to near-normal levels of activity without needing widespread distancing or lockdowns. This would be a profound change from the situation we have been in for the past 18 months.

Practical herd immunity does not mean that we never see any COVID-19. It will likely be with us, just at low enough levels that we will not need to have widespread distancing measures in place to protect the health-care system.


Read more: COVID-19 variants FAQ: How did the U.K., South Africa and Brazil variants emerge? Are they more contagious? How does a virus mutate? Could there be a super-variant that evades vaccines?


What level of immunity (either through vaccination or infection) we need for practical herd immunity is uncertain, but it may be quite high. The original strain of SARS-CoV-2 was highly transmissible and transmission is thought to be higher still for some variants of concern.

Empty vials of Pfizer's COVID-19 vaccine
To achieve two-thirds immunity, 90 per cent of the eligible population would need to be vaccinated or infected naturally. (AP Photo/John Locher)

The amount of immunity we need will also depend on what level of controls we are willing to maintain indefinitely. Continued masking, contact tracing, symptomatic and asymptomatic testing and outbreak control measures will mean we will require less immunity than we would without these in place.

Some estimates suggest that we may need two thirds of the population to be protected either by successful vaccination or natural infection. If 90 per cent of the population is eligible for vaccination, and vaccines are 85 per cent effective against infection, we can obtain this two thirds with about 90 per cent of the eligible population being vaccinated or infected naturally.

The United Kingdom has already exceeded these rates in some age groups. Higher rates are even better, because there is still uncertainty about the level of transmissibility and vaccine efficacy against infection (although research shows they are very good against severe disease). We don’t want to discover that we do not have enough immunity through vaccination and have another serious wave of infection.

Emerging variants

A sticker reading 'I'm COVID-19 vaccinated' from Vancouver Coastal Health
Booster vaccinations will hopefully allow us to maintain long-term practical herd immunity against future variants of COVID-19. THE CANADIAN PRESS/Jonathan Hayward

Higher vaccine uptake will mean there are fewer infections before we reach practical herd immunity. The remaining unvaccinated individuals will be safer, protected indirectly by the immunity of those around them. Outbreaks will be smaller and rarer, and there will be fewer opportunities for vaccine escape variants to arise and spread.

That said, variants of SARS-CoV-2 will continue to emerge, and selection will favour variants that escape our immunity. Vaccine developers will continue to broaden the spectrum of the vaccines that are available, and boosters will hopefully allow us to maintain long-term practical herd immunity.

It’s possible that an immune escape variant will emerge that is severe enough, and transmissible enough, that it will cause a new pandemic for which we do not have even practical herd immunity. But barring that, while we may not be free of COVID-19, we can be confident that in the not-too-distant future it will be manageable when we return to near-normal life.

Caroline Colijn's research group receives funding from the Natural Sciences and Engineering Research Council of Canada, Genome British Columbia, the Michael Smith Foundation for Health Research, the Public Health Agency of Canada and Canada 150 Research Chair program of the Federal Government of Canada.

Paul Tupper's research group receives funding from the Natural Sciences and Engineering Research Council of Canada.

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Stocks

Citadel Settles Suit Alleging Former Senior Trader Shared Its Algorithmic “Secret Sauce”

Citadel Settles Suit Alleging Former Senior Trader Shared Its Algorithmic "Secret Sauce"

Citadel has reached a settlement with the British hedge fund it accused of trying to plunder one of its senior traders in an effort to get to its algorit

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Citadel Settles Suit Alleging Former Senior Trader Shared Its Algorithmic "Secret Sauce"

Citadel has reached a settlement with the British hedge fund it accused of trying to plunder one of its senior traders in an effort to get to its algorithmic "secret sauce".

GSA Capital Partners LLC and Citadel announced the settlement late last week after Citadel accused the fund of obtaining "closely guarded" trading strategies when it hired the employee in question, Vedat Cologlu, according to Bloomberg. 

GSA said of the settlement that the two firms “recognize and respect the importance and value of the other’s rights over their confidential information and intellectual property.”

We first documented that Citadel was suing British hedge fund GSA Capital in January of 2020, after GSA attempted to hire Cologlu, allegedly in hopes of accessing the quant secrets at the core of Citadel's "ABC" automated trading strategy. 

Recall, we wrote back in November of 2020 that Citadel was seeking around $40 million over claims that GSA was able to obtain information on the strategy via texts and WhatsApp.

Citadel argued late last year that GSA "can't unsee" and can't forget the information that was taken from Citadel's secret algorithm. Citadel is also moving to try and block GSA from using their trading model. GSA has argued that they found no "secret sauce" from a high-level description of the structure of a trading algorithm. 

David Craig, a lawyer for Citadel Securities, said in late 2020: “GSA’s most senior managers now know where and how Citadel makes hundreds of millions of dollars in annual revenues. They cannot forget that information, or put it out of their minds.”

He noted that only 15 of Citadel's 3,000 employees ever had access to the "strategic logic" of the strategy. One of those employees was Cologlu, a 2007 Wharton grad and self-described "stat arb trader", who helped operate and administer the models whose "returns were notably high given the low level of risk it took on."

Citadel has claimed its "ABC" quant strategy cost more than $100 million to develop. In its lawsuit, Citadel alleged that the UK fund wanted Cologlu to hand over confidential information about the strategy:

GSA asked for sensitive information on his equity-trading including his profits and the speed of the trades. And then Cologlu handed over a plan that Citadel argues was based on its own confidential model, including the way the algorithm made predictions.

And there's good reason for the information to be coveted. Citadel Securities has been wildly profitable: the company posted a record $6.7 billion in revenue in 2020. This was almost double the previous high in 2018. The blockbuster result came after some of its traders moved from Chicago and New York to set up shop in a Palm Beach hotel in late March 2020 as the pandemic upended lives and markets across the globe. The results of the privately-held company were released in presentation to investors as part of a $2.5 billion loan Citadel Securities was seeking.

The Citadel securities trading arm started as a high-frequency market-maker in options before pushing into equities. Today, the firm dominates that realm and has had a very close relationship with the likes of the millennials' favorite trading platform, Robinhood. We documented back in September 2020 that Citadel now controls 41% of all retail trading. 

GSA was spun out of Deutsche Bank AG in 2005 and manages around $7.5 billion. Citadel’s legal filing names GSA founder and majority owner Jonathan Hiscox as a defendant, alongside other officials including the chief technology officer.

Back in January 2020, we noted the full details of Citadel's lawsuit. 

Tyler Durden Sat, 06/12/2021 - 14:00

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UK Government Adviser Says Mask Mandates Should Continue “Forever”

UK Government Adviser Says Mask Mandates Should Continue "Forever"

Authored by Paul Joseph Watson via Summit News,

A UK government adviser and former Communist Party member Susan Michie says that mask mandates and social distancing should…

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UK Government Adviser Says Mask Mandates Should Continue "Forever"

Authored by Paul Joseph Watson via Summit News,

A UK government adviser and former Communist Party member Susan Michie says that mask mandates and social distancing should continue “forever” and that people should adopt such behaviour just as they did with wearing seatbelts.

Michie, who is a Professor of Health Psychology at UCL and a leading member of SAGE, said such control measures should become part of people’s “normal” routine behaviour.

"Vaccines are a really important part of pandemic control but it is only one part. [A] test, trace and isolate system, [as well as] border controls, are really essential. And the third thing is people’s behaviour. That is, the behaviour of social distancing, of… making sure there’s good ventilation [when you’re indoors], or if there’s not, wearing face masks, and [keeping up] hand and surface hygiene."

"We will need to keep these going in the long term, and that will be good not only for Covid but also to reduce other [diseases] at a time when the NHS is [struggling]… I think forever, to some extent…"

"I think there’s lots of different behaviours that we have changed in our lives. We now routinely wear seatbelts – we didn’t use to. We now routinely pick up dog poo in the parks – we didn’t use to. When people see that there is a threat and there is something they can do to reduce that [to protect] themselves, their loved ones and their communities, what we have seen over this last year is that people do that."

Michie’s comments once again emphasize how many scientific advisers have become drunk on COVID-19 power and never want to relinquish it.

“Unsurprisingly, Channel 5 News made absolutely no effort to scrutinise these claims. The programme’s presenter raised no objection to the idea that mask-wearing and social distancing could continue “forever”, resorting only to friendly laughter,” writes Michael Curzon.

“Professor Michie’s co-panellist, a fellow scientist at UCL, Dr Shikta Das, said:

“I think Susan has made a very good point here,” adding that the vaccine roll-out has created a “false sense of security”.

She concluded:

“I don’t think we are yet ready to unlock.”

How’s all that for balance!

Perhaps unsurprisingly, Michie is known to be a long-time Communist hardliner and was so zealous in her beliefs she garnered the nickname “Stalin’s nanny.”

Her sentiment echoes that of fellow government adviser Professor Neil Ferguson, who once acknowledged that he was surprised authorities were able to “get away with” the same draconian measures that Communist China imposed at the start of the pandemic.

“[China] is a communist one-party state, we said. We couldn’t get away with [lockdown] in Europe, we thought… and then Italy did it. And we realised we could,” said Ferguson.

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Tyler Durden Sat, 06/12/2021 - 11:30

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