Two studies show the accuracy of perception-based systems in detecting disease biomarkers without needing molecular recognition elements, such as antibodies
Researchers from multiple academic and research institutions have collaborated to develop a non-conventional machine learning-based technology for identifying and measuring biomarkers to detect ovarian cancer without the need for molecular identification elements, such as antibodies.
Traditional clinical laboratory methods for detecting biomarkers of specific diseases require a “molecular recognition molecule,” such as an antibody, to match with each disease’s biomarker. However, according to a Lehigh University news release, for ovarian cancer “there’s not a single biomarker—or analyte—that indicates the presence of cancer.
“When multiple analytes need to be measured in a given sample, which can increase the accuracy of a test, more antibodies are required, which increases the cost of the test and the turnaround time,” the news release noted.
Unveiled in two sequential studies, the new method for detecting ovarian cancer uses machine learning to examine spectral signatures of carbon nanotubes to detect and recognize the disease biomarkers in a very non-conventional fashion.
“Carbon nanotubes have interesting electronic properties,” said Daniel Heller, PhD (above), in the Lehigh University news release. “If you shoot light at them, they emit a different color of light, and that light’s color and intensity can change based on what’s sticking to the nanotube. We were able to harness the complexity of so many potential binding interactions by using a range of nanotubes with various wrappings. And that gave us a range of different sensors that could all detect slightly different things, and it turned out they responded differently to different proteins.” This method differs greatly from traditional clinical laboratory methods for identifying disease biomarkers. (Photo copyright: Memorial Sloan-Kettering Cancer Center.)
Perception-based Nanosensor Array for Detecting Disease
In the Science Advances paper, the researchers described their development of “a perception-based platform based on an optical nanosensor array that leverages machine learning algorithms to detect multiple protein biomarkers in biofluids.
“Perception-based machine learning (ML) platforms, modeled after the complex olfactory system, can isolate individual signals through an array of relatively nonspecific receptors. Each receptor captures certain features, and the overall ensemble response is analyzed by the neural network in our brain, resulting in perception,” the researchers wrote.
“This work demonstrates the potential of perception-based systems for the development of multiplexed sensors of disease biomarkers without the need for specific molecular recognition elements,” the researchers concluded.
In the Nature Biomedical Engineering paper, the researchers described a fined-tuned toolset that could accurately differentiate ovarian cancer biomarkers from biomarkers in individuals who are cancer-free.
“Here we show that a ‘disease fingerprint’—acquired via machine learning from the spectra of near-infrared fluorescence emissions of an array of carbon nanotubes functionalized with quantum defects—detects high-grade serous ovarian carcinoma in serum samples from symptomatic individuals with 87% sensitivity at 98% specificity (compared with 84% sensitivity at 98% specificity for the current best [clinical laboratory] screening test, which uses measurements of cancer antigen 125 and transvaginal ultrasonography,” the researchers wrote.
“We demonstrated that a perception-based nanosensor platform could detect ovarian cancer biomarkers using machine learning,” said Yoona Yang, PhD, a postdoctoral research associate in Lehigh’s Department of Chemical and Biomolecular Engineering and co-first author of the Science Advances article, in the news release.
How Perception-based Machine Learning Platforms Work
According to Yang, perception-based sensing functions like the human brain.
“The system consists of a sensing array that captures a certain feature of the analytes in a specific way, and then the ensemble response from the array is analyzed by the computational perceptive model. It can detect various analytes at once, which makes it much more efficient,” Yang said.
“SWCNTs have unique optical properties and sensitivity that make them valuable as sensor materials. SWCNTS emit near-infrared photoluminescence with distinct narrow emission bands that are exquisitely sensitive to the local environment,” the researchers wrote in Science Advances.
“Carbon nanotubes have interesting electronic properties,” said Daniel Heller, PhD, Head of the Cancer Nanotechnology Laboratory at Memorial Sloan Kettering Cancer Center and Associate Professor in the Department of Pharmacology at Weill Cornell Medicine of Cornell University, in the Lehigh University news release.
“If you shoot light at them, they emit a different color of light, and that light’s color and intensity can change based on what’s sticking to the nanotube. We were able to harness the complexity of so many potential binding interactions by using a range of nanotubes with various wrappings. And that gave us a range of different sensors that could all detect slightly different things, and it turned out they responded differently to different proteins,” he added.
The researchers put their technology to practical test in the second study. The wanted to learn if it could differentiate symptomatic patients with high-grade ovarian cancer from cancer-free individuals.
The research team used 269 serum samples. This time, nanotubes were bound with a specific molecule providing “an extra signal in terms of data and richer data from every nanotube-DNA combination,” said Anand Jagota PhD, Professor, Bioengineering and Chemical and Biomolecular Engineering, Lehigh University, in the news release.
This year, 19,880 women will be diagnosed with ovarian cancer and 12,810 will die from the disease, according to American Cancer Society data. While more research and clinical trials are needed, the above studies are compelling and suggest the possibility that one day clinical laboratories may detect ovarian cancer faster and more accurately than with current methods.
This “Virus Trap” might eventually be manufactured by clinical laboratories for the diagnostic process
Clinical laboratory managers and pathologists will be fascinated by this new treatment coming out of Germany for viral infections. It’s an entirely different technology approach to locating and neutralizing live viruses that may eventually be able to control anti-viral-resistant strains of specific viruses as well.
As virologists and microbiologists are aware, even in our present era of technological and medical advances, viral infections are extremely difficult to treat. There are currently no effective antidotes against most viral infections and antibiotics are only successful in fighting bacterial infections.
Thus, this new technology developed by a research team at the Technical University of Munich (TUM) in Munich, Germany, that uses DNA origami to neutralize and trap viruses and render them harmless is sure to gain swift attention, especially given the world’s battle with the SARS-CoV-2 Omicron variant.
“Bacteria have a metabolism. We can attack them in different ways,” said virologist Ulrike Protzer, MD (above), Director of the Institute of Virology at TUM School of Medicine and one of the authors of the study, in a TUM press release. “Viruses, on the other hand, do not have their own metabolism, which is why antiviral drugs are almost always targeted against a specific enzyme in a single virus. Such a development takes time. If the idea of simply mechanically eliminating viruses can be realized, this would be widely applicable and thus an important breakthrough, especially for newly emerging viruses,” she added. (Photo copyright: Helmholtz Munich.)
Entrapping Viruses within 3D Hollow Structures
DNA origami is the nanoscale folding of DNA to create two- and three-dimensional complex shapes that can be manufactured with a high degree of precision at the nanoscale. Researchers have been working with and enhancing this technique for about 15 years.
However, scientists at TUM wondered if they could create such hollow structures based on the capsules that encompass viruses to entrap those viruses. They developed a method that made it possible to create artificial hollow bodies the size of a virus and explored using those hollow bodies as a type of “virus trap.”
The researchers theorized that if those hollow bodies could be lined on the inside with virus-binding molecules, they could tightly bind the viruses and remove them from circulation. For this method to be successful, however, those hollow bodies had to have large enough openings to ensure the viruses could get into the shells.
“None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus—they were simply too small,” said Hendrik Dietz, PhD, Professor of Physics at TUM and an author of the study in a press release. “Building stable hollow bodies of this size was a huge challenge,” he added.
So, the team of researchers used the icosahedron geometric shape, which is an object comprised of 20 sides. They engineered the hollow bodies for their virus trap from three-dimensional, triangular plates which had to have slightly beveled edges to ensure the binding points would assemble properly to the desired objects.
“In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” Dietz explained. “We can now produce objects with up to 180 subunits and achieve yields of up to 95%. The route there was, however, quite rocky, with many iterations.”
By varying the binding points on the edges of the triangles, the scientists were able to create closed hollow spheres and spheres with openings or half-shells that could be utilized as virus traps. They successfully tested their virus traps on adeno-associated viruses (AAV) and hepatitis B viruses in cell cultures.
“Even a simple half-shell of the right size shows a measurable reduction in virus activity,” Dietz stated in the press release. “If we put five binding sites for the virus on the inside—for example suitable antibodies—we can already block the virus by 80%. If we incorporate more, we achieve complete blocking.”
The team irradiated their finished building blocks with ultraviolet (UV) light and then treated the outside with polyethylene glycol and oligolysine. This process prevented the DNA particles from being immediately degraded in body fluids. Those particles were stable in mouse serum for 24 hours. The TUM scientists plan to test their building blocks on living mice soon.
“We are very confident that this material will also be well tolerated by the human body,” Dietz said.
Could Clinical Laboratories Manufacture Components of the Virus Traps?
The researchers noted that the starting materials for their virus traps can be mass produced at a very reasonable cost and may have other uses.
“In addition to the proposed application as a virus trap, our programmable system also creates other opportunities,” Dietz said. “It would also be conceivable to use it as a multivalentantigen carrier for vaccinations, as a DNA or RNA carrier for gene therapy, or as a transport vehicle for drugs.”
There is much research yet to be done on this cutting-edge technology. However, for this therapy to be appropriate for a patient, a specimen of the virus will need to be identified and studied. Then, the DNA origami would be tailored to capture that specific virus. Thus, it’s conceivable that clinical laboratories, if used for the diagnostic step, might also be able to then manufacture the virus trap that is customized to locate, surround, and neutralize that specific virus.
Molecular probes designed to spot minute amounts of pathogens in biological samples may aid clinical laboratories’ speed-to-answer
Driven to find a better way to isolate minute samples of pathogens from among high-volumes of other biological organisms, researchers at Canada’s McMaster University in Hamilton, Ontario, have unveiled a bioinformatics algorithm which they claim shortens time-to-answer and speeds diagnosis of deadly diseases.
Two disease pathogens the researchers specifically targeted in their study are responsible for sepsis and SARS-CoV-2, the coronavirus causing COVID-19. Clinical laboratories would welcome a technology which both shortens time-to-answer and improves diagnostic accuracy, particularly for pathogens such as sepsis and SARS-CoV-2.
Their design of molecular probes that target the genomic sequences of specific pathogens can enable diagnosticians and clinical laboratories to spot extremely small amounts of viral and bacterial pathogens in patients’ biological samples, as well as in the environment and wildlife.
“There are thousands of bacterial pathogens and being able to determine which one is present in a patient’s blood sample could lead to the correct treatment faster when time is very important,” Zachery Dickson, a lead author of the study, told Brighter World. Dickson is a bioinformatics PhD candidate in the Department of Biology at McMaster University. “The probe makes identification much faster, meaning we could potentially save people who might otherwise die,” he added.
Sepsis is a life-threatening response to infection that leads to organ failure, tissue damage, and death in hospitals worldwide. According to Sepsis Alliance, about 30% of people diagnosed with severe sepsis will die without quick and proper treatment. Thus, a “shortcut” to identifying sepsis in its early stages may well save many lives, the McMaster researchers noted.
And COVID-19 has killed millions. Such a tool that identifies sepsis and SARS-CoV-2 in minute biological samples would be a boon to hospital medical laboratories worldwide.
“We currently need faster, cheaper, and more succinct ways to detect pathogens in human and environmental samples that democratize the hunt, and this pipeline does exactly that,” Hendrik Poinar, PhD (above), McMaster Professor of Anthropology and a lead author of the study, told Brighter World. Poinar is Director of the McMaster University Ancient DNA Center. Hospital medical laboratories could help save many lives if sepsis and COVID-19 could be detected earlier. (Graphic copyright: McMaster University.)
Is Bioinformatics ‘Shortcut’ Faster than PCR Testing?
The researchers say their probes enable a shortcut to detection—even in an infection’s early stages—by “targeting, isolating, and identifying the DNA sequences specifically and simultaneously.”
The probes’ design makes possible simultaneous targeted capture of diverse metagenomics targets, Biocompare explained.
But is it faster than PCR (polymerase chain reaction) testing?
The McMaster scientists were motivated by the “challenges of low signal, high background, and uncertain targets that plague many metagenomic sequencing efforts,” they noted in their paper.
They pointed to challenges posed by PCR testing, a popular technique used for detection of sepsis pathogens as well as, more recently, for SARS-CoV-2, the coronavirus causing COVID-19.
“The (PCR) technique relies on primers that bind to nucleic acid sequences specific to an organism or group of organisms. Although capable of sensitive, rapid detection and quantification of a particular target, PCR is limited when multiple loci are targeted by primers,” the researchers wrote in Cell Reports Methods.
According to LabMedica, “A wide array of metagenomic study efforts are hampered by the same challenge: low concentrations of targets of interest combined with overwhelming amounts of background signal. Although PCR or naive DNA capture can be used when there are a small number of organisms of interest, design challenges become untenable for large numbers of targets.”
Detecting Pathogens Faster, Cheaper, and More Accurately
As part of their study, researchers tested two probe sets:
one to target bacterial pathogens linked to sepsis, and
another to detect coronaviruses including SARS-CoV-2.
They were successful in using the probes to capture a variety of pathogens linked to sepsis and SARS-CoV-2.
“We validated HUBDesign by generating probe sets targeting the breadth of coronavirus diversity, as well as a suite of bacterial pathogens often underlying sepsis. In separate experiments demonstrating significant, simultaneous enrichment, we captured SARS-CoV-2 and HCoV-NL63 [Human coronavirus NL 63] in a human RNA background and seven bacterial strains in human blood. HUBDesign has broad applicability wherever there are multiple organisms of interest,” the researchers wrote in Cell Reports Methods.
The findings also have implications to the environment and wildlife, the researchers noted.
Of course, more research is needed to validate the tool’s usefulness in medical diagnostics. The McMaster University researchers intend to improve HUBDesign’s efficiency but note that probes cannot be designed for unknown targets.
Nevertheless, the advanced application of novel technologies to diagnose of sepsis, which causes 250,000 deaths in the US each year, according to the federal Centers for Disease Control and Prevention, is a positive development worth watching.
The McMaster scientists’ discoveries—confirmed by future research and clinical studies—could go a long way toward ending the dire effects of sepsis as well as COVID-19. That would be a welcome development, particularly for hospital-based laboratories.
23andMe executives say they plan to leverage their database of millions of customer genotypes ‘tohelp accelerate personalized healthcare at scale,’ a key goal of precision medicine
In what some financial analysts believe may be an indication that popularity of direct-to-consumer (DTC) genetic testing among customers who seek info on their ethnic background and genetic predisposition to disease is waning, personal genomics/biotechnology company 23andMe announced it has completed its merger with Richard Branson’s VG Acquisition Corp. (NYSE:VGAC) and is now publicly traded on NASDAQ.
According to a 23andMe news release, “The combined company is called 23andMe Holding Co. and will be traded on The Nasdaq Global Select Market (“NASDAQ”) beginning on June 17, 2021, under the new ticker symbol ‘ME’ for its Class A Common shares and ‘MEUSW’ for its public warrants.”
Now that it will file quarterly earnings reports, pathologists and clinical laboratory managers will have the opportunity to learn more about how 23andMe serves the consumer market for genetic types and how it is generating revenue from its huge database containing the genetic sequences from millions of people.
After raising $600 million and being valued at $3.5 billion, CNBC reported that 23andMe’s shares rose by 21% during its first day of trading.
“23andMe is more than just a genetics company. We are an activist brand that is approaching healthcare and drug discovery with the individual at the center, as our partner,” said Anne Wojcicki (above), 23andMe’s co-founder and Chief Executive Officer, during remarks she gave after ringing the opening bell on the company’s first day of public trading, a 23andMe blog post noted. “We are going to continue pioneering a consumer-centered personalized healthcare world. We are going to show that drug discovery can be more efficient when you start with a human genetic insight,” she continued. (Photo copyright: TechCrunch.)
Might the quick rise in its stock price be a sign that 23andMe—with its database of millions of human genotypes—has found a lucrative path forward in drug discovery?
23andMe says that 80% of its 10.7 million genotyped customers have consented to sharing their data for research, MedCity News reported, adding that, “The long-term focus for 23andMe still remains using all of its accumulated DNA data to strike partnerships with pharmaceutical companies.”
Time for a New Direction at 23andMe
While 23andMe’s merger is a recent development, it is not a surprising direction for the Sunnyvale, Calif.-based company, which launched in 2006, to go.
Even prior to the COVID-19 pandemic, both 23andMe and its direct competitor Ancestry had experienced a decline in direct-to-consumer testing sales of at-home DNA and genealogy test kit orders. This decline only accelerated during the pandemic.
Meanwhile, 23andMe Therapeutics, a division focused on research and drug development, has been on the rise, Bloomberg News reported. On its website, 23andMe said it has ongoing studies in oncology, respiratory, and cardiovascular diseases.
“It’s kind of an ideal time for us,” Wojcicki told Bloomberg News.
“There are huge growth opportunities ahead,” said Richard Branson, founder of the Virgin Group, which sponsors the special-purpose acquisition company (SPAC) VG Acquisition Corp., in the 23andMe news release.
In a VG Acquisition Corp. news release, Branson said, “Of the hundreds of companies we reviewed for our SPAC, 23andMe stands head and shoulders above the rest.”
“As an early investor, I have seen 23andMe develop into a company with enormous growth potential. Driven by Anne’s vision to empower consumers, and with our support, I’m excited to see 23andMe make a positive difference to many more people’s lives,” he added.
Report Bullish on Consumer Genetic Testing
Despite the apparent saturation of the direct-to-consumer (DTC) genetic testing market, and consumers’ concerns about privacy, Infiniti Research reported that worldwide sales of DTC tests “are poised to grow by $1.39 bn during 2021-2025, progressing at a CAGR [compound annual growth rate] of over 16% during the forecast period.”
“This study identifies the advances in next-generation genetic sequencing as one of the prime reasons driving the direct-to-consumer genetic testing market growth during the next few years. Also, reduction in the cost of services and growing adoption of online service platforms will lead to sizable demand in the market,” the report states.
Clinical laboratory leaders will want to stay abreast of 23andMe rise as a publicly-traded company. It will be interesting to see if Wojcicki’s vision about moving therapies into clinics in five years comes to fruition.
As many clinical laboratory scientists know, gene sequencing technology continues to become faster, more accurate, and less expensive per whole human genome sequenced
In February, Dark Daily reported that Personalis, Inc. (NASDAQ:PSNL) had delivered its 100,000th whole human genome sequence to the US Department of Veterans Affairs Million Veterans Program (VA MVP). Now, the Menlo Park, Calif.-based cancer genomics company has topped that achievement by delivering its 125,000 whole human genome sequence!
“This represents another important landmark for both the program and for Personalis,” said John West, Chief Executive Officer, Personalis, in a news release. “We congratulate the VA MVP for reaching this important milestone.
“We strongly believe that the research projects being performed today will enable precision medicine in healthcare systems in the future across a wide range of disease areas,” he added. This is a positive development for clinical laboratories, as personalized medicine services require a lab to sequence and interpret the patient’s DNA.
Personalis was contracted with the US federal government to perform genetic research in 2012 and has delivered 50,000 genomes to the VA MVP during the past twelve months.
The Personalis and VA MVP researchers seek to gain a better understanding of how genetic variants affect health. Before the COVID-19 pandemic hit the US, the VA was enrolling veterans in the Million Veterans Program at 63 VA medical centers across the country. There are currently about 830,000 veterans enrolled in the venture and the VA is expecting two million veterans to eventually sign up for the sequencing project.
“As a global leader in genomic sequencing and comprehensive analytics services, Personalis is uniquely suited to lead these population-scale efforts and we are currently in the process of expanding our business operations internationally,” West added.
According to the press release, “the VA MVP provides researchers with a rich resource of genetic, health, lifestyle, and military-exposure data collected from questionnaires, medical records, and genetic analyses. By combining this information into a single database, the VA MVP promises to advance knowledge about the complex links between genes and health.”
NIH All of Us Research Program Supports Precision Medicine Goals Another genetic research project being conducted by the US National Institutes of Health (NIH) is the All of Us Research Program. Using donated personal health information from thousands of participants, the NIH researchers seek to “learn how our biology, lifestyle, and environment affect health,” according to the program’s website.
“We’re changing the paradigm for research,” said Josh Denny, MD (above), Chief Executive Officer of the All of Us Research Program, in an NIH news release. “Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible. We’re working to provide that valuable information in a responsible way,” he added. Clinical laboratories may soon see new precision medicine biomarkers derived from this type of research. (Photo copyright: Vanderbilt University.)
The All of Us Research Program intends to have at least one million US participants take part in the research. The researchers hope to help scientists discover new knowledge regarding how biological, environmental, and behavioral factors influence health, and to learn to tailor healthcare to patients’ specific medical needs, a key component of precision medicine.
Participants in the project share personal information via a variety of methods, including surveys, electronic health records, and biological samples.
A Better Sampling of Under-Represented Communities
Since opening enrollment in 2018, more than 270,000 people have contributed blood, urine, and saliva samples to the All of Us Research Program. More than 80% of the participants come from communities that are traditionally under-represented in biomedical research.
“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, Genomics Program Director, All of Us, in the NIH news release. “Too many groups have been left out of research in the past, so much of what we know about genomics is based mainly on people of European ancestry. And often, genomic data are explored without critical context like environment, economics, and other social determinants of health. We’re trying to help change that, enabling the entire research community to help fill in these knowledge gaps.”
The All of Us Research Project’s analysis of the collected data includes both whole-genome sequencing (WGS) and genotyping and is taking a phased approach in returning genetic data to participants.
Participants initially receive data about their genetic ancestry and traits. That is followed later by health-related results, such as how their genetic variants may increase the risk of certain diseases and how their DNA may affect their reaction to drug therapies.
Genetic researchers hope programs like these will lead to improved in vitro diagnostics and drug therapies. Genetic sequencing also may lead to new diagnostic and therapeutic biomarkers for clinical laboratories.
