Monday, March 11, 2024

 

Deciphering the tip of migrating neurons: Discovery of growth cone in migrating neurons involved in promoting neuronal migration and regeneration in the brain after injury


Migrating neurons possess a growth cone that shares functions with axonal growth cones and regulates neuronal migration by interaction with the extracellular environment



NAGOYA CITY UNIVERSITY

Neuronal growth cone 

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COLLECTIVE TIME-LAPSE IMAGES OF A MIGRATING NEURON (LEFT) AND AN ELONGATING AXON (RIGHT) FROM SUPER-RESOLUTION MICROSCOPY. GROWTH CONES AT THE TIPS OF THE NEURONS ARE EXTENDED WHILE THE CELL BODY MIGRATES AND THE AXON ELONGATES.

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CREDIT: © NAGOYA CITY UNIVERSITY GRADUALTE SCHOOL OF MEDICAL SCIENCES




The structure and functions of the tip of migrating neurons remain elusive. Here, a research group led by Kazunobu Sawamoto, Professor at Nagoya City University and National Institute for Physiological Sciences, and by Chikako Nakajima and Masato Sawada, staff scientists in his laboratory, has found that the PTPσ-expressing growth cone senses the extracellular matrix and drives neuronal migration in the injured brain, leading to functional recovery.

Neural stem cells are present in the postnatal mammalian brain and produce new neurons. New neurons migrate toward injured sites, and promoting neuronal migration results in functional recovery after brain injury. Nevertheless, there is an inhibitory effect on neuronal migration in the injured sites, the mechanisms of which need to be elucidated in order to improve recruitment of new neurons in the injured sites and thus to enhance the recovery after brain injury. The migrating neurons possess an axonal growth cone-like structure at their tip, but the role of this structure in neuronal migration has not been fully understood.

Sawamoto’s group focused on elucidating the function of the growth cone-like structure of migrating neurons of the mouse brain. The researchers used super-resolution microscopy to study the cytoskeletal dynamics and molecular features of the neuronal tip. They showed that the tip structure shares important functions with axonal growth cones. In short, the growth cone of cultured migrating neurons is responsive to external signals through tyrosine phosphatase receptor type sigma (PTPσ) to guide the directionality of migration and initiate the movement of their cell body. The growth cone responds to chondroitin sulfate (CS) through PTPσ and collapses, resulting in inhibition of neuronal migration. In the presence of CS, the growth cones can revert to their extended morphology when they interact with heparan sulfate (HS), thus re-enabling neuronal migration. 

“To investigate whether the effect of HS in reversing the inhibitory effect of CS can promote neuronal migration in the injured brain, it was necessary to apply HS-containing biomaterial to the CS-rich injured brain,” Sawamoto said. 

Next, they employed HS-containing gelatin-fiber nonwoven fabric, a biomaterial that provides structural scaffolds for cells such as migrating neurons. They showed that the applied HS-containing fibers promoted extension of growth cones and neuronal migration in the injured brain. Furthermore, implantation of the HS-enriched gelatin fabric promoted the regeneration of mature neurons and restored neurological functions. These results suggest that elucidating the molecular mechanisms of growth cone-mediated interaction with the local extracellular environment may enable the development of new regeneration technologies based on the promotion of neuronal migration.

Recent studies by other groups have shown that aging alters the physical properties of brain extracellular matrix, including CSPG. 

“Given that the growth cone of migrating neurons serves as a primer for neuronal migration under inhibitory extracellular conditions, it is necessary to further investigate whether the growth cone-mediated treatment to recruit new neurons from the endogenous source to the damaged sites is also applicable to aged brains,” Nakajima commented.

The full findings of the study are published in Nature Communications.
Article title: Identification of the growth cone as a probe and driver of neuronal migration in the injured brain. DOI: 10.1038/s41467-024-45825-8

In addition to Kazunobu Sawamoto, Chikako Nakajima, and Masato Sawada, co-authors of this research article include researchers from Nagoya City University, National Institute for Physiological Sciences, Niigata University, Kyoto University, Doshisha University, Jichi Medical University, The Japan Wool Textile Co., Ltd., Nikke Medical Co., Ltd., Toray Research Center, Inc., New York University, Friedrich Schiller University Jena, University of Valencia, and University of Pennsylvania.

 

New research sets trap for potentially deadly sandfly


Peer-Reviewed Publication

UNIVERSITY OF NOTTINGHAM

Lutzomyia longipalpis sandfly 

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LUTZOMYIA LONGIPALPIS, A SPECIES OF SANDFLY NATIVE TO BRAZIL AND SOUTH AMERICA THAT CAN SPREAD A DISEASE CALLED LEISHMANIASIS. 

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CREDIT: UNIVERSITY OF NOTTINGHAM




Scientists have discovered the specific enzyme that a species of sandfly uses to produce a pheromone attractant, which could lead to the creation of targeted traps to control them and reduce the spread of the potentially fatal disease, Leishmaniasis.

The team from the University of Nottingham’s School of Chemistry analysed the genome of the Lutzomyia longipalpis, a species of sandfly native to Brazil and South America that can spread a disease called Leishmaniasis. 

The study identified the enzyme, called a Terpene Synthase that is responsible for making the terpene pheromone sobralene, that the insect uses to attract others for mating, a discovery that could lead to the development of commercial traps for targeting and controlling this type of sandfly. The research has been published today in PNAS. (link to be added)

Over 90 sandfly species are known to transmit Leishmania parasites that are spread to humans through being bitten, but Lutzomyia longipalpis is the major carrier of the disease in South America. The most common symptoms of the disease are skin ulcers and lesions which can leave life-long scars, in more serious cases people can become very unwell with fever, weight loss, enlargement of the spleen and liver, and anaemia. The most serious form of the disease, known as visceral leishmaniasis, is invariably fatal within 2-years if untreated. Most cases of visceral leishmaniasis occur in Brazil, but the disease can be found in large parts of the tropics and subtropics. 

Terpenes are widely used in nature for chemical communication, but understanding how these structurally diverse natural products are produced by insects is only now beginning to emerge. Males of the sandfly, Lutzomyia longipalpis, use terpene pheromones to lure females and other males to mating sites. 

Terpene synthases are responsible for the biosynthesis of many chemicals used by plants and microorganisms for defense and communication. This research identifies the first insect terpene synthase (TPS) from the insect Lutzomyia. It offers the potential for sustainable production of this compound through biocatalysis.    

Professor Neil Oldham from the University of Nottingham’s School of Chemistry led the study, he said: “Finding this enzyme has been very difficult and we have been hunting for it for over 2 years., The Lutzomyia genome contains an unusually high number of candidate terpene synthase genes, but thanks to the persistence of Dr Charlie Ducker, a talented researcher on the team, we were able to find the one that makes the pheromone.”

“The beauty of the pheromone approach is that it is very specific for this insect and so the next stage of the project will be to engineer microorganisms to make the enzyme in a way that would produce the pheromone. If we can then find a way to scale this up for commercial use this would be a way to control the populations of these insects and hopefully reduce the spread of Leishmaniasis.”

 

Cicadas’ unique urination unlocks new understanding of fluid dynamics


While most small insects and mammals urinate in droplets, cicadas urinate in jets. Georgia Tech researchers say the finding could be used to create better robots and small nozzles



GEORGIA INSTITUTE OF TECHNOLOGY

Unique Urination of Cicadas 

VIDEO: 

SUMMARY OF FINDINGS

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CREDIT: GEORGIA TECH (SAAD BHAMLA/ELIO CHALLITA)




Cicadas are the soundtrack of summer, but their pee is more special than their music. Rather than sprinkling droplets, they emit jets of urine from their small frames. For years, Georgia Tech researchers have wanted to understand the cicada’s unique urination.

Saad Bhamla, an assistant professor in the School of Chemical and Biochemical Engineering, and his research group hoped for an opportunity to study a cicada’s fluid excretion. However, while cicadas are easily heard, they hide in trees, making them hard to observe. As such, seeing a cicada pee is an event. Bhamla’s team had only watched the process on YouTube.

Then, while doing field work in Peru, the team got lucky: They saw numerous cicadas in a tree, peeing.

This moment of observation was enough to disprove two main insect pee paradigms. First, cicadas eat xylem sap, and most xylem feeders only pee in droplets because it uses less energy to excrete the sap. Cicadas, however, are such voracious eaters that individually flicking away each drop of pee would be too taxing and would not extract enough nutrients from the sap.

“The assumption was that if an insect transitions from droplet formation into a jet, it will require more energy because the insect would have to inject more speed,” said Elio Challita, a former Ph.D. student in Bhamla’s lab and current postdoctoral researcher at Harvard University.

Second, smaller animals are expected to pee in droplets because their orifice is too tiny to emit anything thicker. Because of cicadas’ larger size — with wingspans that can rival a small hummingbird’s — they use less energy to expel pee in jets.

“Previously, it was understood that if a small animal wants to eject jets of water, then this becomes a bit challenging, because the animal expends more energy to force the fluid’s exit at a higher speed. This is due to surface tension and viscous forces. But a larger animal can rely on gravity and inertial forces to pee,” Challita said.

The cicadas’ ability to jet water offered the researchers a new understanding of how fluid dynamics impacts these tiny insects —and even large mammals. The researchers published this challenge to the paradigm as a brief, “Unifying Fluidic Excretion Across Life from Cicadas to Elephants,” in Proceedings of the National Academy of Sciences the week of March 11.

For years, the research group has been studying fluid ejection across species, culminating in a recent arXiv preprint that characterizes this phenomenon from microscopic fungi to colossal whales. Their framework reveals diverse functions — such as excretion, venom spraying, prey hunting, spore dispersal, and plant guttation — highlighting potential applications in soft robotics, additive manufacturing, and drug delivery.

Cicadas are the smallest animal to create high-speed jets, so they can potentially inform applications in making jets in tiny robots/nozzles. And because their population reaches trillions, the ecosystem impact of their fluid ejection is substantial but unknown. Beyond bio-inspired engineering, Bhamla believes the critters could also inform bio-monitoring applications. 

 Cicada peeing [VIDEO] |

"Our research has mapped the excretory patterns of animals, spanning eight orders of scale from tiny cicadas to massive elephants,” he said. “We've identified the fundamental constraints and forces that dictate these processes, offering a new lens through which to understand the principles of excretion, a critical function of all living systems. This work not only deepens our comprehension of biological functions but also paves the way for unifying the underlying principles that govern life’s essential processes."

Citation: Elio J. Challita & M. Saad Bhamla. “Unifying Fluidic Excretion Across Life from Cicadas to Elephants,” Proceedings of National Academy of Sciences, March 2024.

 

Natural history specimens have never been so accessible


UTA part of project to make 3D images of 13,000 vertebrates available free online


Peer-Reviewed Publication

UNIVERSITY OF TEXAS AT ARLINGTON

Gregory Pandelis, collections manager of UT Arlington’s Amphibian and Reptile Diversity Research Center 

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GREGORY PANDELIS, COLLECTIONS MANAGER OF UT ARLINGTON’S Amphibian and Reptile Diversity Research Center

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CREDIT: PHOTO COURTESY UT ARLINGTON




With the help of 16 grants from the National Science Foundation, researchers have painstakingly taken computed topography (CT) scans of more than 13,000 individual specimens to create 3D images of more than half of all the world's animal groups, including mammals, fishes, amphibians and reptiles.

The research team, made of members from The University of Texas at Arlington and 25 other institutions, are now a quarter of the way through inputting nearly 30,000 media files to the open-source repository MorphoSource. This will allow researchers and scholars to share findings and improve access to material critical for scientific discovery.

“Thanks to this exciting openVertebrate project, also called oVert, anyone—scientists, researchers, students, teachers, artists—can now look online to research the anatomy of just about any animal imaginable without leaving home,” said Gregory Pandelis, collections manager of UT Arlington’s Amphibian and Reptile Diversity Research Center. “This will help reduce wear and tear on many rare specimens while increasing access to them at the same time.”

A summary of the project has just been published in the peer-reviewed journal BioScience reviewing the specimens that have been scanned to date and offering a glimpse of how the data might be used in the future.

For example, one research team has used the data to conclude that Spinosaurus, a massive dinosaur that was larger than Tyrannosaurus rex and thought to be aquatic, would have actually been a poor swimmer, and thus likely stayed on land. Another study revealed that frogs have evolved to gain and lose the ability to grow teeth more than any other animal.

The value of oVert extends beyond scientific inquiry. Artists are using the 3D models to create realistic animal replicas. Photographs of oVert specimens have been displayed as part of museum exhibits. In addition, specimens have been incorporated into virtual reality headsets that allow users to interact with the animals.

Educators also are able to use oVert models in their classrooms. From the outset of the project, the research team placed a strong emphasis on K-12 outreach, organizing workshops where teachers could learn how to use the data in their classrooms.

“As a kid who loved all things science- and nature-related and had a particular interest in skeletal anatomy, I would go through great pains to collect, preserve and study skulls and other specimens for my childhood natural history collection, the start of my scientific inspiration,” Pandelis said. “Realizing that you could study these things digitally with just a few clicks on a computer was eye-opening for me, and it opened up the path to my current research using CT scans of snake specimens to study their skull evolution. Now, this wealth of data has been opened and made publicly accessible to anyone who has a professional, recreational or educational interest in anatomy and morphology. Natural history specimens have never been so accessible and impactful.”

In the next phase of the research project, the team will be creating sophisticated tools to analyze the data collected. Since researchers have never had digital access to so many 3D natural history specimens before, it will take further developments in machine learning and supercomputing to use them to their full potential.

For a video snapshot of the project, watch this two-minute video.

 

A new sensor detects harmful “forever chemicals” in drinking water


The technology could offer a cheap, fast way to test for PFAS, which have been linked to cancer and other health problems.


MASSACHUSETTS INSTITUTE OF TECHNOLOGY





CAMBRIDGE, MA -- MIT chemists have designed a sensor that detects tiny quantities of perfluoroalkyl and polyfluoroalkyl substances (PFAS) — chemicals found in food packaging, nonstick cookware, and many other consumer products.

These compounds, also known as “forever chemicals” because they do not break down naturally, have been linked to a variety of harmful health effects, including cancer, reproductive problems, and disruption of the immune and endocrine systems.

Using the new sensor technology, the researchers showed that they could detect PFAS levels as low as 200 parts per trillion in a water sample. The device they designed could offer a way for consumers to test their drinking water, and it could also be useful in industries that rely heavily on PFAS chemicals, including the manufacture of semiconductors and firefighting equipment.

“There’s a real need for these sensing technologies. We’re stuck with these chemicals for a long time, so we need to be able to detect them and get rid of them,” says Timothy Swager, the John D. MacArthur Professor of Chemistry at MIT and the senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences.

Other authors of the paper are former MIT postdoc and lead author Sohyun Park and MIT graduate student Collette Gordon.

Detecting PFAS

Coatings containing PFAS chemicals are used in thousands of consumer products. In addition to nonstick coatings for cookware, they are also commonly used in water-repellent clothing, stain-resistant fabrics, grease-resistant pizza boxes, cosmetics, and firefighting foams.

These fluorinated chemicals, which have been in widespread use since the 1950s, can be released into water, air, and soil, from factories, sewage treatment plants, and landfills. They have been found in drinking water sources in all 50 states.

In 2023, the Environmental Protection Agency created an “advisory health limit” for two of the most hazardous PFAS chemicals, known as perfluorooctanoic acid (PFOA) and perfluorooctyl sulfonate (PFOS). These advisories call for a limit of 0.004 parts per trillion for PFOA and 0.02 parts per trillion for PFOS in drinking water.

Currently, the only way that a consumer could determine if their drinking water contains PFAS is to send a water sample to a laboratory that performs mass spectrometry testing. However, this process takes several weeks and costs hundreds of dollars.

To create a cheaper and faster way to test for PFAS, the MIT team designed a sensor based on lateral flow technology — the same approach used for rapid Covid-19 tests and pregnancy tests. Instead of a test strip coated with antibodies, the new sensor is embedded with a special polymer known as polyaniline, which can switch between semiconducting and conducting states when protons are added to the material.

The researchers deposited these polymers onto a strip of nitrocellulose paper and coated them with a surfactant that can pull fluorocarbons such as PFAS out of a drop of water placed on the strip. When this happens, protons from the PFAS are drawn into the polyaniline and turn it into a conductor, reducing the electrical resistance of the material. This change in resistance, which can be measured precisely using electrodes and sent to an external device such as a smartphone, gives a quantitative measurement of how much PFAS is present.

This approach works only with PFAS that are acidic, which includes two of the most harmful PFAS — PFOA and perfluorobutanoic acid (PFBA).

A user-friendly system

The current version of the sensor can detect concentrations as low as 200 parts per trillion for PFBA, and 400 parts per trillion for PFOA. This is not quite low enough to meet the current EPA guidelines, but the sensor uses only a fraction of a milliliter of water. The researchers are now working on a larger-scale device that would be able to filter about a liter of water through a membrane made of polyaniline, and they believe this approach should increase the sensitivity by more than a hundredfold, with the goal of meeting the very low EPA advisory levels.

“We do envision a user-friendly, household system,” Swager says. “You can imagine putting in a liter of water, letting it go through the membrane, and you have a device that measures the change in resistance of the membrane.”

Such a device could offer a less expensive, rapid alternative to current PFAS detection methods. If PFAS are detected in drinking water, there are commercially available filters that can be used on household drinking water to reduce those levels. The new testing approach could also be useful for factories that manufacture products with PFAS chemicals, so they could test whether the water used in their manufacturing process is safe to release into the environment.

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The research was funded by an MIT School of Science Fellowship to Gordon, a Bose Research Grant, and a Fulbright Fellowship to Park.

 

Scientists design bifunctional catalyst to solve environmental pollution problems


Uses 3D POV-based metal-organic framework


Peer-Reviewed Publication

TSINGHUA UNIVERSITY PRESS

Bifunctional Catalyst to Solve Environmental Pollution 

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RESEARCHERS HAVE DEVELOPED A NEW THREE-DIMENSIONAL 2-FOLD INTERPENETRATING POLYOXOVANADATE-BASED METAL-ORGANIC FRAMEWORK THAT SHOWS SATISFYING CATALYTIC PERFORMANCES FOR THE SELECTIVE OXIDATION OF 2-CHLOROETHYL ETHYL SULFIDE (CEES) TO CORRESPONDING SULFOXIDE (CEESO) AND PHOTODEGRADATION TOWARD PHENOL, 2-CHLOROPHENOL AND M-CRESOL UNDER VISIBLE LIGHT.

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CREDIT: POLYOXOMETALATES, TSINGHUA UNIVERSITY PRESS





A team of researchers from Bohai University in China have designed and synthesized a bifunctional catalyst that can solve the environmental pollution caused by mustard gas and phenolic compounds. They synthesized this bifunctional catalyst, a new three-dimensional polyoxovanadate-based metal-organic framework, under hydrothermal conditions.

 

Their work is published in the journal Polyoxometalates on March 4, 2024.

 

The team’s bifunctional catalyst shows satisfying catalytic performances for the selective oxidation of 2-chloroethyl ethyl sulfide (CEES) to corresponding sulfoxide (CEESO) and photodegradation toward phenol, CEES, and m-cresol under visible light. A bifunctional catalyst is one that provides both acidic and basic catalytic functions.

 

In recent years, the problem of organic hazardous substances that cause pollution has raised considerable concern. Scientists have focused their work on developing reasonable methods for degrading these organic hazardous substances. CEES, or mustard gas, is a chemical warfare agent that causes severe skin diseases, strong irritation of the respiratory tract, and even death. Since mustard gas was first used in World War I, researchers have sought ways to detoxify this chemical warfare agent. M-cresol is an organic compound that is extracted from coal tar and is used in the production of other chemicals, including pesticides. It is corrosive to the eyes, skin, and respiratory tract.

 

Phenolic pollutants often persist in polluted waste water that flows from industrial, agricultural, and domestic work. Once they make their way into the water systems, phenolic pollutants can be very harmful to humans and the environment. These pollutants can be acutely toxic to the point of causing the death of animals, birds, or fish. They can also stunt the growth of or kill plants. Scientists have been working to design by synthesis new bifunctional catalysts that can convert these types of dangerous pollutants into low toxicity degradants. However, up to this point in time, scientists had not successfully achieved the preparation of high dimensional interpenetrating metal-organic frameworks that can act as bifunctional catalysts capable of oxidizing CEES to CEESO and degrading phenolic compounds under visible light.

 

Polyoxometalates (POMs) are a kind of inorganic metal oxide clusters with diverse architectural structures and attractive properties. Because of their wide array of structures and functionalities, they are one of the most useful classes of inorganic molecular materials. Within the POMs family, polyoxovanadates (POVs) have attracted increasing attention from scientists because of their diverse structures and remarkable properties.

 

The researchers used a bis-pyridyl-bis-amide ligand to construct the new POV-based metal-organic framework. They then studied the 3D POV-based metal-organic framework using single crystal X-ray diffraction analysis, IR spectroscopy, and powder X-ray diffraction. “The long feature of the amide-based ligand induces the formation of the unusual 2-fold interpenetrating structure,” said Guo-Cheng Liu, an associate professor at Bohai University.

 

The team’s bifunctional catalyst successfully catalyzed the selective oxidation of toxic CEES to the corresponding safer sulfoxide in the presence of H2O2, or hydrogen peroxide, as an eco-friendly oxidant. It worked under visible light with an effective recyclability and stability. The successful conversion was greater than 99 percent and the selectivity was 97 percent.

 

In addition, the bifunctional catalyst showed excellent photocatalytic degradation activity toward phenol, CEES, and m-cresol under visible light. The team successfully achieved degradation efficiencies above 92.6 percent for 140 minutes. They also investigated in detail the photocatalytic reaction kinetics, the mechanisms of photodegradation, and recycling capability of phenol. “This work provides important guidance for the development of new POVs-based bifunctional catalysts for the decontamination in water,” said Liu.

 

The research team includes Shuang Li, Yuan Zheng, Guo-Cheng Liu, Xiao-Hui Li, Zhong Zhang, and Xiu-Li Wang from the Liaoning Professional Technology Innovation Center of Liaoning Province for Conversion Materials of Solar Cell, College of Chemistry and Materials Engineering, Bohai University, China.

 

The research is funded by the National Natural Science Foundation of China and the Natural Science Foundation and Education Department of Liaoning Province.

 


About Polyoxometalates  

Polyoxometalates is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of polyoxometalates, featured in rapid review and fast publishing, sponsored by Tsinghua University and published by Tsinghua University Press. Submissions are solicited in all topical areas, ranging from basic aspects of the science of polyoxometalates to practical applications of such materials. Polyoxometalates offers readers an attractive mix of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats, Comments, and Highlight.

About SciOpen 

SciOpen is a professional open access resource for discovery of scientific and technical content published by the Tsinghua University Press and its publishing partners, providing the scholarly publishing community with innovative technology and market-leading capabilities. SciOpen provides end-to-end services across manuscript submission, peer review, content hosting, analytics, and identity management and expert advice to ensure each journal’s development by offering a range of options across all functions as Journal Layout, Production Services, Editorial Services, Marketing and Promotions, Online Functionality, etc. By digitalizing the publishing process, SciOpen widens the reach, deepens the impact, and accelerates the exchange of ideas.


Mathematicians use AI to identify emerging COVID-19 variants


Peer-Reviewed Publication

UNIVERSITY OF MANCHESTER

Stylised image of a CLASSIX clustering result overlaid on top of a coronavirus illustration 

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STYLISED IMAGE OF A CLASSIX CLUSTERING RESULT OVERLAID ON TOP OF A CORONAVIRUS ILLUSTRATION (SOURCE: https://phil.cdc.gov/Details.aspx?pid=23312)

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CREDIT: SOURCE: HTTPS://PHIL.CDC.GOV/DETAILS.ASPX?PID=23312




Scientists at The Universities of Manchester and Oxford have developed an AI framework that can identify and track new and concerning COVID-19 variants and could help with other infections in the future.

The framework combines dimension reduction techniques and a new explainable clustering algorithm called CLASSIX, developed by mathematicians at The University of Manchester. This enables the quick identification of groups of viral genomes that might present a risk in the future from huge volumes of data.

The study, presented this week in the journal PNAS, could support traditional methods of tracking viral evolution, such as phylogenetic analysis, which currently require extensive manual curation.

Roberto Cahuantzi, a researcher at The University of Manchester and first and corresponding author of the paper, said: “Since the emergence of COVID-19, we have seen multiple waves of new variants, heightened transmissibility, evasion of immune responses, and increased severity of illness.

“Scientists are now intensifying efforts to pinpoint these worrying new variants, such as alpha, delta and omicron, at the earliest stages of their emergence. If we can find a way to do this quickly and efficiently, it will enable us to be more proactive in our response, such as tailored vaccine development and may even enable us to eliminate the variants before they become established.”

Like many other RNA viruses, COVID-19 has a high mutation rate and short time between generations meaning it evolves extremely rapidly. This means identifying new strains that are likely to be problematic in the future requires considerable effort.

Currently, there are almost 16 million sequences available on the GISAID database (the Global Initiative on Sharing All Influenza Data), which provides access to genomic data of influenza viruses.

Mapping the evolution and history of all COVID-19 genomes from this data is currently done using extremely large amounts of computer and human time.

The described method allows automation of such tasks. The researchers processed 5.7 million high-coverage sequences in only one to two days on a standard modern laptop; this would not be possible for existing methods, putting identification of concerning pathogen strains in the hands of more researchers due to reduced resource needs.

Thomas House, Professor of Mathematical Sciences at The University of Manchester, said: “The unprecedented amount of genetic data generated during the pandemic demands improvements to our methods to analyse it thoroughly. The data is continuing to grow rapidly but without showing a benefit to curating this data, there is a risk that it will be removed or deleted.

“We know that human expert time is limited, so our approach should not replace the work of humans all together but work alongside them to enable the job to be done much quicker and free our experts for other vital developments.”

The proposed method works by breaking down genetic sequences of the COVID-19 virus into smaller “words” (called 3-mers) represented as numbers by counting them. Then, it groups similar sequences together based on their word patterns using machine learning techniques.

Stefan Güttel, Professor of Applied Mathematics at the University of Manchester, said: “The clustering algorithm CLASSIX we developed is much less computationally demanding than traditional methods and is fully explainable, meaning that it provides textual and visual explanations of the computed clusters.”

Roberto Cahuantzi added: “Our analysis serves as a proof of concept, demonstrating the potential use of machine learning methods as an alert tool for the early discovery of emerging major variants without relying on the need to generate phylogenies.

“Whilst phylogenetics remains the ‘gold standard’ for understanding the viral ancestry, these machine learning methods can accommodate several orders of magnitude more sequences than the current phylogenetic methods and at a low computational cost.”