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Viruses are doing mysterious things everywhere – AI can help researchers understand what they’re up to in the oceans and in your gut

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theconversation.com – Libusha , Associate Professor of and Computational Biology, Microbiology and Immunology, Albert Einstein College of Medicine – 2024-05-15 07:16:41

Many viral genetic sequences code for proteins that researchers haven't seen before.

KTSDesign/Science Photo Library via Getty Images

Libusha Kelly, Albert Einstein College of Medicine

Viruses are a mysterious and poorly understood force in microbial ecosystems. Researchers know they can infect, kill and manipulate human and bacterial cells in nearly every environment, from the oceans to your gut. But scientists don't yet have a full picture of how viruses affect their surrounding environments in large part because of their extraordinary diversity and ability to rapidly evolve.

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Communities of microbes are difficult to study in a laboratory setting. Many microbes are challenging to cultivate, and their natural has many more features influencing their or failure than scientists can replicate in a lab.

So systems biologists like me often sequence all the DNA present in a sample – for example, a fecal sample from a patient – separate out the viral DNA sequences, then annotate the sections of the viral genome that code for proteins. These notes on the location, structure and other features of genes researchers understand the functions viruses might carry out in the environment and help identify different kinds of viruses. Researchers annotate viruses by matching viral sequences in a sample to previously annotated sequences available in public databases of viral genetic sequences.

However, scientists are identifying viral sequences in DNA collected from the environment at a rate that far outpaces our ability to annotate those genes. This means researchers are publishing findings about viruses in microbial ecosystems using unacceptably small fractions of available data.

To improve researchers' ability to study viruses around the globe, my team and I have developed a novel approach to annotate viral sequences using artificial intelligence. Through protein language models akin to large language models like ChatGPT but specific to proteins, we were able to classify previously unseen viral sequences. This the door for researchers to not only learn more about viruses, but also to address biological questions that are difficult to answer with current techniques.

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Annotating viruses with AI

Large language models use relationships between words in large datasets of text to potential answers to questions they are not explicitly “taught” the answer to. When you ask a chatbot “What is the capital of France?” for example, the model is not looking up the answer in a table of capital . Rather, it is using its training on huge datasets of documents and information to infer the answer: “The capital of France is Paris.”

Similarly, protein language models are AI algorithms that are trained to recognize relationships between billions of protein sequences from environments around the world. Through this training, they may be able to infer something about the essence of viral proteins and their functions.

We wondered whether protein language models could answer this question: “Given all annotated viral genetic sequences, what is this new sequence's function?”

In our proof of concept, we trained neural networks on previously annotated viral protein sequences in pre-trained protein language models and then used them to predict the annotation of new viral protein sequences. Our approach allows us to probe what the model is “seeing” in a particular viral sequence that leads to a particular annotation. This helps identify candidate proteins of interest either based on their specific functions or how their genome is arranged, winnowing down the search of vast datasets.

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Microscopy image of spherical bacteria colored bright green

Prochlorococcus is one of the many species of marine bacteria with proteins that researchers haven't seen before.

Anne Thompson/Chisholm Lab, MIT via Flickr

By identifying more distantly related viral gene functions, protein language models can complement current methods to provide new insights into microbiology. For example, my team and I were able to use our model to discover a previously unrecognized integrase – a type of protein that can move genetic information in and out of cells – in the globally abundant marine picocyanobacteria Prochlorococcus and Synechococcus. Notably, this integrase may be able to move genes in and out of these populations of bacteria in the oceans and enable these microbes to better adapt to changing environments.

Our language model also identified a novel viral capsid protein that is widespread in the global oceans. We produced the first picture of how its genes are arranged, showing it can contain different sets of genes that we believe indicates this virus serves different functions in its environment.

These preliminary findings represent only two of thousands of annotations our approach has provided.

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Analyzing the unknown

Most of the hundreds of thousands of newly discovered viruses remain unclassified. Many viral genetic sequences match protein families with no known function or have never been seen before. Our work shows that similar protein language models could help study the threat and promise of our planet's many uncharacterized viruses.

While our study focused on viruses in the global oceans, improved annotation of viral proteins is critical for better understanding the role viruses play in and disease in the human body. We and other researchers have hypothesized that viral activity in the human gut microbiome might be altered when you're sick. This means that viruses may help identify stress in microbial communities.

However, our approach is also limited because it requires high-quality annotations. Researchers are developing newer protein language models that incorporate other “tasks” as part of their training, particularly predicting protein structures to detect similar proteins, to make them more powerful.

Making all AI tools available via FAIR Data Principles – data that is findable, accessible, interoperable and reusable – can help researchers at large realize the potential of these new ways of annotating protein sequences leading to discoveries that benefit human health.The Conversation

Libusha Kelly, Associate Professor of Systems and Computational Biology, Microbiology and Immunology, Albert Einstein College of Medicine

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This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Conversation

Vaccines tell a success story that Robert F. Kennedy Jr. and Trump forget – here are some key reminders

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theconversation.com – Mark R. O'Brian, Professor and Chair of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo – 2024-07-26 07:11:29
Many fatal childhood illnesses can be prevented with vaccination.
Halfpoint Images/Moment via Getty Images

Mark R. O'Brian, University at Buffalo

Vaccinations have provided significant protection for the public against infectious diseases. However, there was a modest decrease in support in 2023 nationwide for vaccine requirements for to attend .

In addition, the presidential candidacy of Robert F. Kennedy Jr., a leading critic of childhood vaccination, has given him a prominent platform in which to amplify his views. This includes an extensive interview on the “Joe Rogan Experience,” a podcast with over 14 million subscribers. Notably, former President Donald Trump has said he is opposed to mandatory school COVID-19 vaccinations, and in a phone call Trump apparently wasn't aware was being recorded, he appeared to endorse Kennedy's views toward vaccines.

I am a biochemist and molecular biologist studying the roles microbes play in and disease. I also teach medical and am interested in how the public understands science.

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Here are some facts about vaccines that skeptics like Kennedy get wrong:

Vaccines are effective and safe

Public health data from 1974 to the present conclude that vaccines have saved at least 154 million lives worldwide over the past 50 years. Vaccines are also constantly monitored for safety in the U.S.

Nevertheless, the false claim that vaccines cause autism persists despite study after study of large populations throughout the world showing no causal link between them.

Claims about the dangers of vaccines often come from misrepresenting scientific research papers. Kennedy cites a 2005 report allegedly showing massive brain inflammation in monkeys in response to vaccination, when in fact the authors of that study that there were no serious medical complications. A separate 2003 study that Kennedy claimed showed a 1,135% increase in autism in vaccinated versus unvaccinated children actually found no consistent significant association between vaccines and neurodevelopmental outcomes.

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Kennedy also claims that a 2002 vaccine study included a control group of children 6 months of age and younger who were fed mercury-contaminated tuna sandwiches. This claim is false.

Gloved hands of clinician placing bandaid on child's arm, a syringe and vaccine vial beside them
Vaccines are continuously monitored for safety before and long after they're available to the general public.
Elena Zaretskaya/Moment via Getty Images

Aluminum adjuvants help boost immunity

Kennedy is co-counsel with a law firm that is suing the pharmaceutical company Merck based in part on the unfounded assertion that the aluminum in one of its vaccines causes neurological disease. Aluminum is added to many vaccines as an adjuvant to strengthen the body's immune response to the vaccine, thereby enhancing the body's defense against the targeted microbe.

The law firm's claim is based on a 2020 report showing that brain tissue from some with Alzheimer's disease, autism and multiple sclerosis have elevated levels of aluminum. The authors of that study do not assert that vaccines are the source of the aluminum, and vaccines are unlikely to be the culprit.

Notably, the brain samples analyzed in that study were from 47- to 105-year-old patients. Most people are exposed to aluminum primarily through their diets, and aluminum is eliminated from the body within days. Therefore, aluminum exposure from childhood vaccines is not expected to persist in those patients.

Vaccines undergo the same approval process as other drugs

Clinical trials for vaccines and other are blinded, randomized and placebo-controlled studies. For a vaccine trial, this means that participants are randomly divided into one group that receives the vaccine and a second group that receives a placebo saline solution. The researchers carrying out the study, and sometimes the participants, do not know who has received the vaccine or the placebo until the study has finished. This eliminates bias.

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Results are published in the public domain. For example, vaccine trial data for COVID-19, human papilloma virus and rotavirus is available for anyone to access.

Vaccine manufacturers are liable for injury or death

Kennedy's lawsuit against Merck contradicts his insistence that vaccine manufacturers are fully immune from litigation.

His claim is based on an incorrect interpretation of the National Vaccine Injury Compensation Program, or VICP. VICP is a no-fault federal program created to reduce frivolous lawsuits against vaccine manufacturers, which threaten to cause vaccine shortages and a resurgence of vaccine-preventable disease.

A person claiming injury from a vaccine can petition the U.S. Court of Federal Claims through the VICP for monetary compensation. If the VICP petition is denied, the claimant can then sue the vaccine manufacturer.

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Gloved hand picking up vaccine vial among a tray of vaccine vials
Drug manufacturers are liable for any vaccine-related or injury.
Andreas Ren Photography Germany/Image Source via Getty Images

The majority of cases resolved under the VICP end in a negotiated settlement between parties without establishing that a vaccine was the cause of the claimed injury. Kennedy and his law firm have incorrectly used the payouts under the VICP to assert that vaccines are unsafe.

The VICP gets the vaccine manufacturer off the hook only if it has complied with all requirements of the Federal Food, Drug and Cosmetic Act and exercised due care. It does not protect the vaccine maker from claims of fraud or withholding information regarding the safety or efficacy of the vaccine during its development or after approval.

Good nutrition and sanitation are not substitutes for vaccination

Kennedy asserts that populations with adequate nutrition do not need vaccines to avoid infectious diseases. While it is clear that improvements in nutrition, sanitation, treatment, food safety and public health measures have played important roles in reducing deaths and severe complications from infectious diseases, these factors do not eliminate the need for vaccines.

After World War II, the U.S. was a wealthy nation with substantial health-related infrastructure. Yet, Americans reported an average of 1 million cases per year of now-preventable infectious diseases.

Vaccines introduced or expanded in the 1950s and 1960s against diseases like diphtheria, pertussis, tetanus, measles, polio, mumps, rubella and Haemophilus influenza type B have resulted in the near or complete eradication of those diseases.

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It's easy to forget why many infectious diseases are rarely encountered . The success of vaccines does not always tell its own story. It must be retold again and again to counter misinformation.The Conversation

Mark R. O'Brian, Professor and Chair of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Tagging seals with sensors helps scientists track ocean currents and a changing climate

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theconversation.com – Lilian (Lily) Dove, Postdoctoral Fellow of Oceanography, Brown – 2024-07-25 07:08:14

Tagging seals with sensors helps scientists track ocean currents and a changing climate

Lilian Dove, Brown University

A surprising technique has helped scientists observe how Earth's oceans are changing, and it's not using specialized robots or artificial intelligence. It's tagging seals.

Several species of seals around and on Antarctica and regularly dive more than 100 meters in search of their next meal. These seals are experts at swimming through the vigorous ocean currents that make up the Southern Ocean. Their tolerance for deep waters and ability to navigate rough currents make these adventurous creatures the perfect research assistants to oceanographers like my colleagues and me study the Southern Ocean.

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Seal sensors

Researchers have been attaching tags to the foreheads of seals for the past two decades to collect data in remote and inaccessible regions. A researcher tags the seal during mating season, when the marine mammal comes to shore to rest, and the tag remains attached to the seal for a year.

A researcher glues the tag to the seal's head – tagging seals does not affect their behavior. The tag detaches after the seal molts and sheds its fur for a new coat each year.

The tag collects data while the seal dives and transmits its location and the scientific data back to researchers via satellite when the seal surfaces for .

First proposed in 2003, seal tagging has grown into an international collaboration with rigorous sensor accuracy standards and broad data sharing. Advances in satellite technology now allow scientists to have near-instant access to the data collected by a seal.

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New scientific discoveries aided by seals

The tags attached to seals typically carry pressure, temperature and salinity sensors, all properties used to assess the ocean's rising temperatures and changing currents. The sensors also often contain chlorophyll fluorometers, which can data about the 's phytoplankton concentration.

Phytoplankton are tiny organisms that form the base of the oceanic food web. Their presence often means that animals such as fish and seals are around.

The seal sensors can also tell researchers about the effects of climate change around Antarctica. Approximately 150 tons of ice melts from Antarctica every year, contributing to global sea-level rise. This melting is driven by warm water carried to the ice shelves by oceanic currents.

With the data collected by seals, oceanographers have described some of the physical pathways this warm water travels to reach ice shelves and how currents transport the resulting melted ice away from glaciers.

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Seals regularly dive under sea ice and near glacier ice shelves. These regions are challenging, and can even be dangerous, to sample with traditional oceanographic methods.

Across the open Southern Ocean, away from the Antarctic coast, seal data has also shed light on another pathway causing ocean warming. Excess heat from the atmosphere moves from the ocean surface, which is in contact with the atmosphere, down to the interior ocean in highly localized regions. In these , heat moves into the deep ocean, where it can't be dissipated out through the atmosphere.

The ocean stores most of the heat energy put into the atmosphere from human activity. So, understanding how this heat moves around helps researchers monitor oceans around the globe.

Seal behavior shaped by ocean physics

The seal data also provides marine biologists with information about the seals themselves. Scientists can determine where seals look for food. Some regions, called fronts, are hot spots for elephant seals to hunt for food.

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In fronts, the ocean's circulation creates turbulence and mixes water in a way that brings nutrients up to the ocean's surface, where phytoplankton can use them. As a result, fronts can have phytoplankton blooms, which attract fish and seals.

Scientists use the tag data to see how seals are adapting to a changing climate and warming ocean. In the short term, seals may benefit from more ice melt around the Antarctic continent, as they tend to find more food in coastal areas with holes in the ice. Rising subsurface ocean temperatures, however, may change where their prey is and ultimately threaten seals' ability to thrive.

Seals have helped scientists understand and observe some of the most remote regions on Earth. On a changing planet, seal tag data will continue to provide observations of their ocean , which has vital implications for the rest of Earth's climate system.The Conversation

Lilian Dove, Postdoctoral Fellow of Oceanography, Brown University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The Conversation

Cheesemaking is a complex science – a food chemist explains the process from milk to mozzarella

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theconversation.com – John A. Lucey, Professor of Food Science, University of Wisconsin- – 2024-07-24 07:18:57
Storing cheese wheels to let them age intensifies the flavor.
AP Photo/Antonio Calanni

John A. Lucey, University of Wisconsin-Madison

Cheese is a relatively simple food. It's made with milk, enzymes – these are proteins that can chop up other proteins – bacterial cultures and salt. Lots of complex chemistry goes into the cheesemaking process, which can determine whether the cheese turns out soft and gooey like mozzarella or hard and fragrant like Parmesan.

In fact, humans have been making cheese for about 10,000 years. Roman soldiers were given cheese as part of their rations. It is a nutritious food that provides protein, calcium and other minerals. Its long shelf allows it to be transported, traded and shipped long distances.

I am a food scientist at the University of Wisconsin who has studied cheese chemistry for the past 35 years.

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In the U.S., cheese is predominantly made with cow's milk. But you can also find cheese made with milk from other animals like sheep, goats and even buffalo and yak.

Unlike with yogurt, another fermented dairy product, cheesemakers whey – which is water – to make cheese. Milk is about 90% water, whereas a cheese like cheddar is less than about 38% water.

Removing water from milk to make cheese results in a harder, firmer product with a longer shelf life, since milk is very perishable and spoils quickly. Before the invention of refrigeration, milk would quickly sour. Making cheese was a way to preserve the nutrients in milk so you could eat it weeks or months in the future.

How is cheese made?

All cheesemakers first pump milk into a cheese vat and add a special enzyme called rennet. This enzyme destabilizes the proteins in the milk – the proteins then aggregate together and make a gel. The cheesemaker is essentially turning milk from a liquid into a gel.

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After anywhere from 10 minutes to an hour, depending on the type of cheese, the cheesemaker cuts this gel, typically into cubes. Cutting the gel helps some of the whey, or water, separate from the cheese curd, which is made of aggregated milk and looks like a yogurt gel. Cutting the gel into cubes lets some water escape from the newly cut surfaces through small pores, or openings, in the gel.

The cheesemaker's goal is to remove as much whey and moisture from the curd as they need to for their specific recipe. To do so, the cheesemaker might stir or heat up the curd, which helps release whey and moisture. Depending on the type of cheese made, the cheesemaker will drain the whey and water from the vat, leaving behind the cheese curds.

A man in a white lab coat, hairnet and gloves pulls a device through a large tub of white liquid.
Wisconsin Master Cheesemaker Gary Grossen cuts a vat of cheese with a cheese harp during a cheesemaking short course at the Center for Dairy Research in Madison, Wis. Cutting helps release whey during the cheesemaking .
UW Center for Dairy Research

For a harder cheese like cheddar, the cheesemaker adds salt directly to the curds while they're still in the vat. Salting the curds expels more whey and moisture. The cheesemaker then packs the curds together in forms or hoops – these are containers that shape the curds into a block or wheel and hold them there – and places them under pressure. The pressure squeezes the curds in these hoops, and they knit together to form a solid block of cheese.

Cheesemakers salt other cheeses, like mozzarella, by placing them in a salt solution called a brine. The cheese block or wheel floats in a brine tank for hours, days or even weeks. During that time, the cheese absorbs some of the salt, which adds flavor and protects against unwanted bacterial or pathogen growth.

A graphic showing the many steps between a farmer harvesting milk from cows and the cheese reaching the consumer.
The cheese production process.
UW Center for Dairy Research

Cheese is a living, fermented food

While the cheesemaker is completing all these steps, several important bacterial processes are occurring. The cheesemaker adds cheese cultures, which are bacteria they choose that produce specific flavors, at the beginning of the process. Adding them to the milk while it is still liquid gives the bacteria time to ferment the lactose in the milk.

Historically, cheesemakers used raw milk, and the bacteria in the raw milk soured the cheese. Now, cheesemakers use pasteurization, a mild heat treatment that destroys any pathogens present in the raw milk. But using this treatment means the cheesemakers need to add back in some bacteria called starters – these “start” the fermentation process.

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Pasteurization provides a more controlled process for the cheesemaker, as they can select specific bacteria to add, rather than whatever is present in the raw milk.
Essentially, these bacteria eat (ferment) the sugar – the lactose – and in doing so produce lactic acid, as well as other desirable flavor compounds in the cheese like diacetyl, which smells like hot buttered popcorn.

In some types of cheese, these cultures stay active in the cheese long after it leaves the cheese vat. Many cheesemakers age their cheeses for weeks, months or even years to give the fermentation process more time to develop the desired flavors. Aged cheeses include Parmesan, aged cheddars and Gouda.

A person in a white coat holds a wheel of cheese.
A Wisconsin cheesemaker inspects a wheel of Parmesan in the aging room. Aging is an important step in the production of many cheeses, as it allows for flavor .
The Dairy Farmers of Wisconsin

In essence, cheesemaking is a milk concentration process. Cheesemakers want their final product to have the milk proteins, fat and nutrients, without as much of the water. For example, the main milk protein that is captured in the cheesemaking process is casein. Milk might contain about 2.5% casein content, but a finished cheese like cheddar may contain about 25% casein (protein). So cheese contains lots of nutrients protein, calcium and fat.

Infinite possibilities with cheese

There are hundreds of different varieties of cow's milk cheese made across the globe, and they all start with milk. All of these different varieties are produced by adjusting the cheesemaking process.

For some cheeses, like Limburger, the cheesemaker rubs a smear – a solution containing various types of bacteria – on the cheese's surface during the aging process. For others, like Camembert, the cheesemaker places the cheese in an (e.g., a cave) that encourages mold growth.

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Others like bandaged cheddar are wrapped with bandages or covered with ash. Adding a bandage or ash onto the cheese's surface helps protect it from excessive mold growth, and it reduces the amount of moisture lost to evaporation. This creates a harder cheese with stronger flavors.

A man in a white apron and hat stands in a room full of shelves stacked with cheese.
Wisconsin Master Cheesemaker Joe Widmer in his brick cheese aging room. Brick cheese is a smear-ripened cheese – it is produced by applying a salt solution to the exterior of the cheese as it ages.
Dairy Farmers of Wisconsin

Over the past 60 years, cheesemakers have figured out how to select the right bacterial cultures to make cheese with specific flavors and textures. The possibilities are endless, and there's no limit to the cheesemaker's imagination.The Conversation

John A. Lucey, Professor of Food Science, University of Wisconsin-Madison

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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