Screening and analysis of ocean samples also identified a possible missing link in how the RNA viruses evolved
An international team of scientists has used genetic screening and machine learning techniques to identify more than 5,500 previously unknown species of marine RNA viruses and is proposing five new phyla (biological groups) of viruses. The latter would double the number of RNA virus phyla to 10, one of which may be a missing link in the early evolution of the microbes.
Though the newly-discovered viruses are not currently associated with human disease—and therefore do not drive any current medical laboratory testing—for virologists and other microbiologists, “a fuller catalog of these organisms is now available to advance scientific understanding of how viruses evolve,” said Dark Daily Editor-in-Chief Robert Michel.
“While scientists have cataloged hundreds of thousands of DNA viruses in their natural ecosystems, RNA viruses have been relatively unstudied,” wrote four microbiologists from Ohio State University (OSU) who participated in the study in an article they penned for The Conversation.
The OSU study authors included:
Ahmed Zayed, PhD, research scientist, Dept. of Microbiology, OSU.
Matthew Sullivan, PhD, Professor of Microbiology and Director of the Center of Microbiome Science at OSU.
“RNA viruses are clearly important in our world, but we usually only study a tiny slice of them—the few hundred that harm humans, plants and animals,” explained Matthew Sullivan, PhD (above), Director, Center of Microbiome Science, in an OSU news story. Sullivan led the OSU research team. “We wanted to systematically study them on a very big scale and explore an environment no one had looked at deeply, and we got lucky because virtually every species was new, and many were really new,” he added. (Photo copyright: University of Ohio.)
RNA versus DNA Viruses
In contrast to the better-understood DNA virus, an RNA virus contains RNA instead of DNA as its genetic material, according to Samanthi Udayangani, PhD, in an article she penned for Difference Between. Examples of RNA viruses include:
One major difference, she explains, is that RNA viruses mutate at a higher rate than do DNA viruses.
The OSU scientists identified the new species by analyzing a database of RNA sequences from plankton collected during a series of ocean expeditions aboard a French schooner owned by the Tara Ocean Foundation.
“Plankton are any aquatic organisms that are too small to swim against the current,” the authors explained in The Conversation. “They’re a vital part of ocean food webs and are common hosts for RNA viruses.”
The team’s screening process focused on the RNA-dependent RNA polymerase (RdRp) gene, “which has evolved for billions of years in RNA viruses, and is absent from other viruses or cells,” according to the OSU news story.
“RdRp is supposed to be one of the most ancient genes—it existed before there was a need for DNA,” Zayed said.
The RdRp gene “codes for a particular protein that allows a virus to replicate its genetic material. It is the only protein that all RNA viruses share because it plays an essential role in how they propagate themselves. Each RNA virus, however, has small differences in the gene that codes for the protein that can help distinguish one type of virus from another,” the study authors explained.
The screening “ultimately identified over 44,000 genes that code for the virus protein,” they wrote.
Identifying Five New Phyla
The researchers then turned to machine learning to organize the sequences and identify their evolutionary connections based on similarities in the RdRp genes.
“The more similar two genes were, the more likely viruses with those genes were closely related,” they wrote.
The technique classified many of the sequences within the five previously known phyla of RNA viruses:
But the researchers also identified five new phyla—including two dubbed “Taraviricota” and “Arctiviricota”—that “were particularly abundant across vast oceanic regions,” they wrote. Taraviricota is named after the Tara expeditions and Arctiviricota gets its name from the Arctic Ocean.
They speculated that Taraviricota “might be the missing link in the evolution of RNA viruses that researchers have long sought, connecting two different known branches of RNA viruses that diverged in how they replicate.”
In addition to the five new phyla, the researchers are proposing at least 11 new classes of RNA viruses, according to the OSU story. The scientists plan to issue a formal proposal to the International Committee on Taxonomy of Viruses (ICTV), the body responsible for classification and naming of viruses.
Studying RNA Viruses Outside of Disease Environments
“As the COVID-19 pandemic has shown, RNA viruses can cause deadly diseases. But RNA viruses also play a vital role in ecosystems because they can infect a wide array of organisms, including microbes that influence environments and food webs at the chemical level,” wrote the four study authors in The Conversation. “Mapping out where in the world these RNA viruses live can help clarify how they affect the organisms driving many of the ecological processes that run our planet. Our study also provides improved tools that can help researchers catalog new viruses as genetic databases grow.”
This remarkable study, which was partially funded by the US National Science Foundation, will be most intriguing to virologists and microbiologists. However, clinical laboratories also should be interested in the fact that the catalog of known viruses has just expanded by 5,500 types of RNA viruses.
International research team that developed swarm learning believe it could ‘significantly promote and accelerate collaboration and information exchange in research, especially in the field of medicine’
“Swarm Learning” is a technology that enables cross-site analysis of population health data while maintaining patient privacy protocols to generate improvements in precision medicine. That’s the goal described by an international team of scientists who used this approach to develop artificial intelligence (AI) algorithms that seek out and identify lung disease, blood cancer, and COVID-19 data stored in disparate databases.
Since 80% of patient records feature clinical laboratory test results, there’s no doubt this protected health information (PHI) would be curated by the swarm learning algorithms.
In their study they wrote, “Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine. … However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking, and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning.”
What is Swarm Learning?
Swarm Learning is a way to collaborate and share medical research toward a goal of advancing precision medicine, the researchers stated.
The technology blends AI with blockchain-based peer-to-peer networking to create information exchange across a network, the DZNE news release explained. The machine learning algorithms are “trained” to detect data patterns “and recognize the learned patterns in other data as well,” the news release noted.
“Medical research data are a treasure. They can play a decisive role in developing personalized therapies that are tailored to each individual more precisely than conventional treatments,” said Joachim Schultze, MD (above), Director, Systems Medicine at DZNE and Professor, Life and Medical Sciences Institute at the University of Bonn, in the news release. “It’s critical for science to be able to use such data as comprehensively and from as many sources as possible,” he added. This, of course, would include clinical laboratory test results data. (Photo copyright: University of Bonn.)
Since, as Dark Daily has reported many times, clinical laboratory test data comprises as much as 80% of patients’ medical records, such a treasure trove of information will most likely include medical laboratory test data as well as reports on patient diagnoses, demographics, and medical history. Swarm learning incorporating laboratory test results may inform medical researchers in their population health analyses.
“The key is that all participants can learn from each other without the need of sharing confidential information,” said Eng Lim Goh, PhD, Senior Vice President and Chief Technology Officer for AI at Hewlett Packard Enterprise (HPE), which developed base technology for swarm learning, according to the news release.
An HPE blog post notes that “Using swarm learning, the hospital can combine its data with that of hospitals serving different demographics in other regions and then use a private blockchain to learn from a global average, or parameter, of results—without sharing actual patient information.
“Under this model,” the blog continues, “‘each hospital is able to predict, with accuracy and with reduced bias, as though [it has] collected all the patient data globally in one place and learned from it,’ Goh says.”
Swarm Learning Applied in Study
The researchers studied four infectious and non-infectious diseases:
They used 16,400 transcriptomes from 127 clinical studies and assessed 95,000 X-ray images.
Data for transcriptomes were distributed over three to 32 blockchain nodes and across three nodes for X-rays.
The researchers “fed their algorithms with subsets of the respective data set” (such as those coming from people with disease versus healthy individuals), the news release noted.
Findings included:
90% algorithm accuracy in reporting on healthy people versus those diagnosed with diseases for transcriptomes.
76% to 86% algorithm accuracy in reporting of X-ray data.
Methodology worked best for leukemia.
Accuracy also was “very high” for tuberculosis and COVID-19.
X-ray data accuracy rate was lower, researchers said, due to less available data or image quality.
“Our study thus proves that swarm learning can be successfully applied to very different data. In principle, this applies to any type of information for which pattern recognition by means of artificial intelligence is useful. Be it genome data, X-ray images, data from brain imaging, or other complex data,” Schultze said in the DZNE news release.
The scientists say hospitals as well as research institutions may join or form swarms. So, hospital-based medical laboratory leaders and pathology groups may have an opportunity to contribute to swarm learning. According to Schultze, sharing information can go a long way toward “making the wealth of experience in medicine more accessible worldwide.”
Further development of this novel technology could result in new, more sensitive assays for clinical laboratories to use in the effort to improve antimicrobial stewardship in hospitals
Researchers at McMaster University in Ontario, Canada, have used artificial intelligence (AI) to identify a potential antibiotic that neutralizes the drug-resistant bacteria Acinetobacter baumannii, an antibiotic resistant pathogen commonly found in many hospitals. This will be of interest to clinical laboratory managers and microbiologists involved in identifying strains of bacteria to determine if they are antimicrobial-resistant (AMR) superbugs.
Using machine learning, the scientists screened thousands molecules to look for those that inhibited the growth of this specific pathogen. And they succeeded.
“We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii,” the researchers wrote in their published study.
They discovered that the molecule abaucin inhibited the growth of the antibiotic-resistant pathogen in vitro.
This shows how machine learning and AI technologies are giving biomedical researchers tools to identify new therapeutic drugs that are effective against drug-resistant strains of bacteria. This same research can be expected to lead to new clinical laboratory assays that determine if superbugs can be attacked by specific therapeutic drugs.
“When I think about AI in general, I think of these models as things that are just going to help us do the thing we’re going to do better,” Jonathan Stokes, PhD, Assistant Professor of Biomedicine and Biochemistry at McMaster University in Ontario, Canada, and lead author of the study, told USA Today. Clinical laboratory scientists and microbiologists will be encouraged by the McMaster University scientists’ findings. (Photo copyright: McMaster University.)
McMaster Study Details
Jonathan Stokes, PhD, head of the Stokes Laboratory at McMaster University, is Assistant Professor of Biomedicine/Biochemistry at McMaster and lead author of the study. Stokes’ team worked with researchers from the Broad Institute of MIT and Harvard to explore the effectiveness of AI in combating superbugs, USA Today reported.
“This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen,” the researchers wrote in Nature Chemical Biology.
Stokes Lab utilized the high-throughput drug screening technique, spending weeks growing and exposing Acinetobacter baumannii to more than 7,500 agents of drugs and active ingredients of drugs. When 480 compounds were uncovered that blocked the growth of bacteria, this information was then provided to a computer that was trained to run an AI algorithm, CNN reported.
“Once we had our [machine learning] model trained, what we could do then is start showing that model brand-new pictures of chemicals that it had never seen, right? And based on what it had learned during training, it would predict for us whether those molecules were antibacterial or not,” Stokes told CNN.
The model spent hours screening more than 6,000 molecules. It then narrowed the search to 240 chemicals, which were tested in the lab. The scientists pared down the results to the nine most effective inhibitors of bacteria. They then eliminated those that were either related to existing antibiotics or might be considered dangerous.
The researchers found one compound—RS102895 (abaucin)—which, according to Stokes, was likely created to treat diabetes, CNN reported. The scientists discovered that the compound prevented bacterial components from making their way from inside a cell to the cell’s surface.
“It’s a rather interesting mechanism and one that is not observed amongst clinical antibiotics so far as I know,” Stokes told CNN.
Because of the effectiveness of the antibiotic during testing on mice skin, the researchers believe this method may be useful for creating antibiotics custom made to battle additional drug resistant pathogens, CNN noted.
Defeating a ‘Professional Pathogen’
Acinetobacter baumannii (A. baumannii)—the focus of Stoke’s study—is often found on hospital counters and doorknobs and has a sneaky way of using other organisms’ DNA to resist antibiotic treatment, according to CNN.
“It’s what we call in the laboratory a professional pathogen,” Stokes told CNN.
A. baumannii causes infections in the urinary tract, lungs, and blood and typically wreaks havoc to vulnerable patients on breathing machines, in intensive care units, or undergoing surgery, USA Today reported.
A. baumannii is resistant to carbapenem, a potent antibiotic. The Centers for Disease Control and Prevention (CDC) reported that in 2017 the bacteria infected 8,500 people in hospitals, 700 of those infections being fatal.
Further, in its 2019 “Antibiotic Resistance Threats in the United States” report, the CDC stated that one out of every four patients infected with the bacteria died within one month of their diagnosis. The federal agency deemed the bacteria “of greatest need” for new antibiotics.
Thus, finding a way to defeat this particularly nasty bacteria could save many lives.
Implications of Study Findings on Development of new Antibiotics
The Stokes Laboratory study findings show promise. If more antibiotics worked so precisely, it’s possible bacteria would not have a chance to become resistant in the first place, CNN reported.
Next steps in Stokes’ research include optimizing the chemical structure and testing in larger animals or humans, USA Today reported.
“It’s important to remember [that] when we’re trying to develop a drug, it doesn’t just have to kill the bacterium,” Stokes noted. “It also has to be well tolerated in humans and it has to get to the infection site and stay at the infection site long enough to elicit an effect,” USA Today reported.
Stokes’ study is a prime example of how AI can make a big impact in clinical laboratory diagnostics and treatment.
“We know broad-spectrum antibiotics are suboptimal and that pathogens have the ability to evolve and adjust to every trick we throw at them … AI methods afford us the opportunity to vastly increase the rate at which we discover new antibiotics, and we can do it at a reduced cost. This is an important avenue of exploration for new antibiotic drugs,” Stokes told CNN.
Clinical laboratory managers and microbiologists may want to keep an open-mind about the use of AI in drug development. More research is needed to give substance to the McMaster University study’s findings. But the positive results may lead to methods for fine tuning existing antibiotics to better combat antimicrobial-resistant bacteria, USA Today reported.
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