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.
Scientists working to sequence all 1.66 million animal species say this is a missed opportunity to better understand our own genetics; such research would identify biomarkers useful for clinical laboratory testing
For 23 years, the world’s genomic scientists have been on a mission to sequence the genomes of all animal species. And they’ve made great progress. However, according to a recent study conducted by researchers at Washington State University (WSU) and Brigham Young University (BYU), only a fraction of the sequences are from invertebrate species. And that, according to the study’s authors, is “overlooking huge swathes of diversity and opportunity.”
The push to sequence the whole genomes of all animals began in 1998 with the sequencing of the Caenorhabditis elegans roundworm, according to a WSU news release. It was the first animal genome sequence, but it was not to be the last. Nearly 25 years later, genomic scientists have sequenced about 3,300 animal genomes. And while that’s a lot of genomic sequences, it’s a drop in bucket of the approximately 1.7 million animal species on the planet.
But here’s where the missed opportunity comes in. According to the WSU news release, “Vertebrates account for 54% of all genome sequencing assemblies, despite representing only 3.9% of animal species. In contrast, the invertebrates of the Arthropoda phylum, which includes insects and spiders, comprise only 34% of current datasets while representing 78.5% of all species.”
“We are interested in ourselves, and that’s not necessarily a bad thing,” said Paul Frandsen, PhD (above), in the news release. Frandsen is Assistant Professor of Genetics, Genomics, and Biotechnology at Brigham Young University and one of the study authors. “But to begin to understand entire ecosystems,” he continued, “we have to start sampling more of the variety of life to gain a clearer picture. Vertebrates are important components of ecosystems, but arguably insects and many other small creatures probably play an even more important role because they’re down at the base of the food web.” (Photo copyright: Brigham Young University.)
The scientists analyzed the best available genome assemblies found in GenBank, the world’s most extensive genetic database. They found that 3,278 unique animal species across 24 phyla, 64 classes, and 258 orders have been sequenced and assembled to date.
They also found that sequencing efforts have focused heavily on species that most resemble humans. The Hominidae, a taxonomic family of primates that includes humans as well as great apes, bonobos, chimpanzees, orangutans, and gorillas, has the most contiguous genome data assembled.
The team discovered that vertebrates account for 54% of the animal genome sequencing that has been performed even though they make up less than four percent of known animal species. By comparison, invertebrates of the Arthropoda phylum, which represent 78.5% of all animal species, comprise only 34% of the completed animal genome sequencing. And yet, the Arthropoda phylum is the largest phylum in the animal kingdom and includes insects, spiders, scorpions, centipedes, millipedes, crabs, crayfish, lobsters, and barnacles.
“With genome assemblies accumulating rapidly, we want to think about where we are putting our efforts. It’s not being spread evenly across the animal tree of life,” said lead author Scott Hotaling, PhD, post-doctoral researcher at WSU, in the news release. “Invertebrates are still very underrepresented, which makes sense given that people seem to care more about vertebrates, the so-called ‘charismatic megafauna.’”
The team discovered that only five arthropod groups: ants, bees, butterflies, fruit flies, and mosquitos, were well represented in genome sequencing. The longest genome sequenced so far belongs to the Australian lungfish, the only surviving member of the family Neoceratodontidae.
1,100 Years to Sequence All Eukaryotic Life
The scientists also discerned that animal genome assemblies have been produced by 52 countries on every continent with permanent inhabitants. The majority of animal genome sequencing (77%) that is being performed is mostly occurring in developed countries located in the Northern Hemisphere, often referred to as the Global North. Nearly 70% of all animal genome assemblies have been produced by just three countries: the United States, China, and Switzerland.
There are geographic differences between regions regarding the types of animals being sequenced and assembled with North America concentrating on mammals and insects, Europe focusing on fish, and birds being the main type of animals sequenced in Asia.
The scientists would like to see more animal genome sequencing happening in countries from the Global South, or Southern Hemisphere, particularly in tropical regions that contain a myriad of diversity among animal species.
“If we want to build a global discipline, we need to include a global people,” Hotaling said. “It’s just basic equity, and from a pure scientific standpoint, the people who live in areas where species are being sequenced have a lot of knowledge about those species and ecosystems. They have a lot to contribute.”
But the WSU/BYU scientists found that many species in GenBank only have low-quality assemblies available. They noted that “the quality of a genome assembly is likely the most important factor dictating its long-term value.”
Fortunately, several animal genome sequencing ventures have been announced in recent years, so the amount of available data is expected to rise exponentially. These projects include:
The Earth BioGenome Project (EBP) which aspires to sequence and catalog the genes of all the eukaryotic species on the planet within ten years.
The Vertebrate Genomes Project which seeks to generate high-quality assemblies for 70,000 extant vertebrate species.
The Bird 10K Project that seeks to generate assemblies for all extant birds.
The i5K Project which plans to produce 5,000 arthropod genome assemblies.
The authors of the PNAS paper noted that there are currently only about four genome assemblies happening each day and, at that rate, the sequencing of all eukaryotic life will not be completed until the year 3130.
So, microbiologists, clinical laboratory professionals, and genomic scientists have plenty of time to get up to speed.
Given the large number of mutations found in the SARS-CoV-2 Omicron variant, experts in South Africa speculate it likely evolved in someone with a compromised immune system
As the SARS-CoV-2 Omicron variant spreads around the United States and the rest of the world, infectious disease experts in South Africa have been investigating how the variant developed so many mutations. One hypothesis is that it evolved over time in the body of an immunosuppressed person, such as a cancer patient, transplant recipient, or someone with uncontrolled human immunodeficiency virus infection (HIV).
One interesting facet in the story of how the Omicron variant was being tracked as it emerged in South Africa is the role of several medical laboratories in the country that reported genetic sequences associated with Omicron. This allowed researchers in South Africa to more quickly identify the growing range of mutations found in different samples of the Omicron virus.
“Normally your immune system would kick a virus out fairly quickly, if fully functional,” Linda-Gail Bekker, PhD, of the Desmond Tutu Health Foundation (formerly the Desmond Tutu HIV Foundation) in Cape Town, South Africa, told the BBC.
“In someone where immunity is suppressed, then we see virus persisting,” she added. “And it doesn’t just sit around, it replicates. And as it replicates it undergoes potential mutations. And in somebody where immunity is suppressed that virus may be able to continue for many months—mutating as it goes.”
Multiple factors can suppress the immune system, experts say, but some are pointing to HIV as a possible culprit given the likelihood that the variant emerged in sub-Saharan Africa, which has a high population of people living with HIV.
Li “was among the first to detail extensive coronavirus mutations in an immunosuppressed patient,” the LA Times reported. “Under attack by HIV, their T cells are not providing vital support that the immune system’s B cells need to clear an infection.”
Linda-Gail Bekker, PhD (above), of the Desmond Tutu Health Foundation cautions that these findings should not further stigmatize people living with HIV. “It’s important to stress that people who are on anti-retroviral medication—that does restore their immunity,” she told the BBC. (Photo copyright: Test Positive Aware Network.)
Omicron Spreads Rapidly in the US
Genomics surveillance Data from the CDC’s SARS-CoV-2 Tracking system indicates that on Dec. 11, 2021, Omicron accounted for about 7% of the SARS-CoV-2 variants in circulation, the agency reported. But by Dec. 25, the number had jumped to nearly 60%. The data is based on sequencing of SARS-CoV-2 by the agency as well as commercial clinical laboratories and academic laboratories.
Experts have pointed to several likely factors behind the variant’s high rate of transmission. The biggest factor, NPR reported, appears to be the large number of mutations on the spike protein, which the virus uses to attach to human cells. This gives the virus an advantage in evading the body’s immune system, even in people who have been vaccinated.
“The playing field for the virus right now is quite different than it was in the early days,” Joshua Schiffer, MD, of the Fred Hutchinson Cancer Research Center, told NPR. “The majority of variants we’ve seen to date couldn’t survive in this immune environment.”
One study from Norway cited by NPR suggests that Omicron has a shorter incubation period than other variants, which would increase the transmission rate. And researchers have found that it multiplies more rapidly than the Delta variant in the upper respiratory tract, which could facilitate spread when people exhale.
Using Genomics Testing to Determine How Omicron Evolved
But how did the Omicron variant accumulate so many mutations? In a story for The Atlantic, virologist Jesse Bloom, PhD, Professor, Basic Sciences Division, at the Fred Hutchinson Cancer Research Center in Seattle, described Omicron as “a huge jump in evolution,” one that researchers expected to happen “over the span of four or five years.”
Hence the speculation that it evolved in an immunosuppressed person, perhaps due to HIV, though that’s not the only theory. Another is “that the virus infected animals of some kind, acquired lots of mutations as it spread among them, and then jumped back to people—a phenomenon known as reverse zoonosis,” New Scientist reported.
Still, experts are pointing to emergence in someone with a weakened immune system as the most likely cause. One of them, the L.A. Times reported, is Tulio de Oliveira, PhD, Affiliate Professor in the Department of Global Health at the University of Washington. Oliveira leads the Centre for Epidemic Response and Innovation at Stellenbosch University in South Africa, as well as the nation’s Network for Genomic Surveillance.
The Network for Genomic Surveillance, he told The New Yorker, consists of multiple facilities around the country. Team members noticed what he described as a “small uptick” in COVID cases in Gauteng, so on Nov. 19 they decided to step up genomic surveillance in the province. One private clinical laboratory in the network submitted “six genomes of a very mutated virus,” he said. “And, when we looked at the genomes, we got quite worried because they discovered a failure of one of the probes in the PCR testing.”
Looking at national data, the scientists saw that the same failure was on the rise in PCR (Polymerase chain reaction) tests, prompting a request for samples from other medical laboratories. “We got over a hundred samples from over thirty clinics in Gauteng, and we started genotyping, and we analyzed the mutation of the virus,” he told The New Yorker. “We linked all the data with the PCR dropout, the increase of cases in South Africa and of the positivity rate, and then we began to see it might be a very suddenly emerging variant.”
Oliveira’s team first reported the emergence of the new variant to the World Health Organization, on Nov. 24. Two days later, the WHO issued a statement that named the newly classified Omicron variant (B.1.1.529) a “SARS-CoV-2 Variant of Concern.”
Microbiologists and clinical laboratory specialists in the US should keep close watch on Omicron research coming out of South Africa. Fortunately, scientists today have tools to understand the genetic makeup of viruses that did not exist at the time of SARS 2003, Swine flu 2008/9, MERS 2013.
Genomic sequencing continues to benefit patients through precision medicine clinical laboratory treatments and pharmacogenomic therapies
EDITOR’S UPDATE—Jan. 26, 2022: Since publication of this news briefing, officials from Genomics England contacted us to explain the following:
The “five million genome sequences” was an aspirational goal mentioned by then Secretary of State for Health and Social Care Matt Hancock, MP, in an October 2, 2018, press release issued by Genomics England.
As of this date a spokesman for Genomics England confirmed to Dark Daily that, with the initial goal of 100,000 genomes now attained, the immediate goal is to sequence 500,000 genomes.
This goal was confirmed in a tweet posted by Chris Wigley, CEO at Genomics England.
In accordance with this updated input, we have revised the original headline and information in this news briefing that follows.
What better proof of progress in whole human genome screening than the announcement that the United Kingdom’s 100,000 Genome Project has not only achieved that milestone, but will now increase the goal to 500,000 whole human genomes? This should be welcome news to clinical laboratory managers, as it means their labs will be positioned as the first-line provider of genetic data in support of clinical care.
Many clinical pathologists here in the United States are aware of the 100,000 Genome Project, established by the National Health Service (NHS) in England (UK) in 2012. Genomics England’s new goal to sequence 500,000 whole human genomes is to pioneer a “lasting legacy for patients by introducing genomic sequencing into the wider healthcare system,” according to Technology Networks.
The importance of personalized medicine and of the power of precise, accurate diagnoses cannot be understated. This announcement by Genomics England will be of interest to diagnosticians worldwide, especially doctors who diagnose and treat patients with chronic and life-threatening diseases.
Building a Vast Genomics Infrastructure
Genetic sequencing launched the era of precision medicine in healthcare. Through genomics, drug therapies and personalized treatments were developed that improved outcomes for all patients, especially those suffering with cancer and other chronic diseases. And so far, the role of genomics in healthcare has only been expanding, as Dark Daily covered in numerous ebriefings.
Genomics England, which is wholly owned by the Department of Health and Social Care in the United Kingdom, was formed in 2012 with the goal of sequencing 100,000 whole genomes of patients enrolled in the UK National Health Service. That goal was met in 2018, and now the NHS aspires to sequence 500,000 genomes.
“The last 10 years have been really exciting, as we have seen genetic data transition from being something that is useful in a small number of contexts with highly targeted tests, towards being a central part of mainstream healthcare settings,” Richard Scott, MD, PhD (above), Chief Medical Officer at Genomics England told Technology Networks. Much of the progress has found its way into clinical laboratory testing and precision medicine diagnostics. (Photo copyright: Genomics England.)
Genomics England’s initial goals included:
To create an ethical program based on consent,
To set up a genomic medicine service within the NHS to benefit patients,
To make new discoveries and gain insights into the use of genomics, and
To begin the development of a UK genomics industry.
To gain the greatest benefit from whole genome sequencing (WGS), a substantial amount of data infrastructure must exist. “The amount of data generated by WGS is quite large and you really need a system that can process the data well to achieve that vision,” said Richard Scott, MD, PhD, Chief Medical Officer at Genomics England.
In early 2020, Weka, developer of the WekaFS, a fully parallel and distributed file system, announced that it would be working with Genomics England on managing the enormous amount of genomic data. When Genomics England reached 100,000 sequenced genomes, it had already gathered 21 petabytes of data. The organization expects to have 140 petabytes by 2023, notes a Weka case study.
Putting Genomics England’s WGS Project into Action
WGS has significantly impacted the diagnosis of rare diseases. For example, Genomics England has contributed to projects that look at tuberculosis genomes to understand why the disease is sometimes resistant to certain medications. Genomic sequencing also played an enormous role in fighting the COVID-19 pandemic.
Scott notes that COVID-19 provides an example of how sequencing can be used to deliver care. “We can see genomic influences on the risk of needing critical care in COVID-19 patients and in how their immune system is behaving. Looking at this data alongside other omics information, such as the expression of different protein levels, helps us to understand the disease process better,” he said.
What’s Next for Genomics Sequencing?
As the research continues and scientists begin to better understand the information revealed by sequencing, other areas of scientific study like proteomics and metabolomics are becoming more important.
“There is real potential for using multiple strands of data alongside each other, both for discovery—helping us to understand new things about diseases and how [they] affect the body—but also in terms of live healthcare,” Scott said.
Along with expanding the target of Genomics England to 500,000 genomes sequenced, the UK has published a National Genomic Strategy named Genome UK. This plan describes how the research into genomics will be used to benefit patients. “Our vision is to create the most advanced genomic healthcare ecosystem in the world, where government, the NHS, research and technology communities work together to embed the latest advances in patient care,” according to the Genome UK website.
Clinical laboratories professionals with an understanding of diagnostics will recognize WGS’ impact on the healthcare industry. By following genomic sequencing initiatives, such as those coming from Genomics England, pathologists can keep their labs ready to take advantage of new discoveries and insights that will improve outcomes for patients.
One key finding of interest to clinical laboratory scientists is that this research study indicates that the human microbiome may more closely correlate with blood markers of metabolic disease than the genome of individuals
In the search for more sensitive diagnostic biomarkers (meaning the ability to detect disease with smaller samples and smaller quantities of the target biomarker), an international team of researchers has teased out a finding that a panel of multiple biomarkers in the human microbiome is more closely correlated with metabolic disease than genetic markers.
The team also discovered that the foods an individual ate had a more powerful impact on their microbiomes than their genes. The study participants included several sets of identical twins. The researchers found that identical twins shared only about 34% of the same gut microbes. People who were unrelated shared 30% of the same gut microbes.
This is a fascinating insight for pathologists and microbiologists involved in the study of the human microbiome for use in development of precision medicine clinical laboratory testing and drug therapies.
Microbiome Markers for Obesity, Heart Disease, and More
The study began in 2018, when an international team of researchers analyzed the gut microbiomes, diets, and blood biomarkers for cardiometabolic health obtained from 1,100 mostly healthy adults in the United Kingdom (UK) and the United States (US). They collected blood samples from the participants before and after meals to examine blood sugar levels, hormones, cholesterol, and inflammation levels. Sleep and activity levels also were monitored. Participants had to wear a continuous glucose monitor for two weeks during the research period.
The scientists discovered that the composition of a healthy gut microbiome is strongly linked to certain foods, food groups, nutrients, and diet composition. They identified markers for obesity, impaired glucose tolerance, and cardiovascular disease in the gut bacteria.
“When you eat, you’re not just nourishing your body, you’re feeding the trillions of microbes that live inside your gut,” genetic epidemiologist Tim Spector, MD, FmedSCi, told Labroots. Spector is a professor of genetic epidemiology at King’s College London and one of the authors of the study.
The scientists found that a diet rich in nutrient-dense, whole foods was more beneficial to a healthy gut microbiome, which can be an indicator of good health. Individuals who ate minimally processed foods, such as vegetables, nuts, eggs, and seafood were more likely to have healthy gut bacteria than individuals who consumed large amounts of highly processed foods, like juices and other sweetened beverages, processed meats, and refined grains and foods that were high in added sugars and salt.
“It goes back to the age-old message of eating as many whole and unprocessed foods as possible,” Sarah Berry, PhD, a nutrition scientist at King’s College London and a co-author of the study told The New York Times. “What this research shows for the first time is the link between the quality of the food we’re eating, the quality of our microbiomes, and ultimately our health outcomes,” she added.
The researchers concluded that heavily processed foods tend to contain very minimal amounts of fiber, a macronutrient that helps promote good bacteria in the gut microbiome and leads to better metabolic and cardiovascular health.
They found that people who had healthy blood sugar levels following a meal had higher levels of good bacteria called Prevotella copri, a genus of gram-negative bacteria, and Blastocystis, a genus of single-celled heterokont parasites, present in their guts. These bacteria are associated with lower levels of visceral fat, which accumulates around internal organs and increases risk of heart disease.
These “good” microbes also are affiliated with lower levels of inflammation, better blood sugar control, and lower spikes in blood fat and cholesterol levels after meals.
“We were surprised to see such large, clear groups of what we informally call ‘good’ and ‘bad’ microbes emerging from our analysis,” Nicola Segata, PhD (above), told News Medical. Segata is a professor and principal investigator at the Computational Metagenomics Lab at the University of Trento in Italy, and co-author of the study. “It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health,” he added. Pathologists and clinical laboratory scientists who read Dark Daily are already familiar with the plethora of ways the human microbiome is being studied for use in diagnostic testing and drug therapy. (Photo copyright: University of Trento.)
The study also found that different people have wildly varying metabolic responses to the same foods, partially due to the types of bacteria residing in their gut microbiome. The consumption of some foods is better for overall health than other foods, but there is no definitive, one-size-fits-all diet that works for everyone.
“What we found in our study was that the same diet in two different individuals does not lead to the same microbiome, and it does not lead to the same metabolic response. There is a lot of variation,” Andrew Chan, MD, Professor of Medicine at Harvard Medical School, told The New York Times. Chan is also Chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital and co-author of the study.
Small Changes in Diet, Big Impact to Health
The team is now planning a clinical trial to test whether changes in diet can alter levels of good and bad microbes in the gut. If proven to be true, such information could help clinicians design personalized nutritional plans that would enable individuals to improve their gut microbiome and their overall health.
“As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting,” Berry told News Medical. “Given the highly personalized composition of each individual’s microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology.
“We think there are lots of small changes that people can make that can have a big impact on their health that might be mediated through the microbiome,” Berry told The New York Times.
More research and clinical trials are needed before diagnostic tests that use microbiome biomarkers to detect metabolic diseases can be developed. But these early research findings are a sign to pathologists and clinical laboratory managers that microbiome-based assays may come to play a more significant role in the early detection of several metabolic diseases.
Teams from multiple Swedish organizations are investigating the relationship of protein-coding genes to antibodies
Scientists in Sweden are discovering new ways to map the expression of genes in cells, tissues, and organs within the human body thanks to advances in molecular profiling. Their study has successfully combined the analysis of single-cell transcriptomics with spatial antibody-based protein profiling to produce a high-resolution, single-cell mapping of human tissues.
The data links protein-coding genes to antibodies, which could help researchers develop clinical laboratory tests that use specific antibodies to identify and target infectious disease. Might this also lead to a new menu of serology tests that could be used by medical laboratories?
This research is another example of how various databases of genetic and proteomic information—different “omics”—are being combined to produce new understanding of human biology and physiology.
In a Human Protein Atlas (HPA) project press release, Director of the HPA consortium and Professor of Microbiology at Royal Institute of Technology in Stockholm, Mathias Uhlén, PhD, said, “The [Science Advances] paper describes an important addition to the Human Protein Atlas (HPA) which has become one of the world’s most visited biological databases, harboring millions of web pages with information about all the human protein coding genes.”
“We are excited that the new open-access Single Cell Type section constitutes a unique resource for studying the cell type specificity and exact spatial localization of all our proteins”, said Cecilia Lindskog, PhD (above), Head of the HPA Tissue Atlas and Associate Professor, Experimental Pathology, Uppsala University, in the Protein Atlas press release. Medical laboratories may soon have new serology tests to perform that were developed based on HPA data. (Photo copyright: Human Uterus Cell Atlas.)
Distinct Expression Clusters Consistent to Similar Cell Types
To perform their research, the scientists mapped the gene expression profile of all protein-coding genes across different cell types. Their analysis showed that there are distinct expression clusters which are consistent to cell types sharing similar functions within the same organs and between organs of the human body.
The scientists examined data from non-diseased human tissues and organs using three main criteria:
Publicly available raw data from human tissues containing good technical quality with at least 4,000 cells analyzed and at least 20 million read counts by the sequencing for each tissue.
High correlation between pseudo-bulk transcriptomics profile from the scRNA-Seq data and bulk RNA-Seq generated as part of the Human Protein Atlas (HPA).
High correlation between the cluster-specific expression and the expected expression pattern of an extensive selection of marker genes representing well-known tissue- and cell type-specific markers, including both markers from the original publications and additional markers used in pathology diagnostics.
According to the HPA press release, “across all analyzed cell types, almost 14,000 genes showed an elevated expression in particular cell types, out of which approximately 2,000 genes were found to be specific for only one of the cell types.”
The press release also states, “cell types in testis showed the highest numbers of cell type elevated genes, followed by ciliated cells. Interestingly, only 11% of the genes were detected in all analyzed cell types suggesting that the number of essential genes (‘house-keeping’) are surprisingly few.”
Omics-based Biomarkers for Accurate Diagnosis of Disease
The Human Protein Atlas is the largest and most comprehensive database for spatial distribution of proteins in human tissues and cells. It provides a valuable tool for researchers who study and analyze protein localization and expression in human tissues and cells.
Ongoing improvements in gene sequencing technologies are making research of genes more accurate, faster, and more economical. Advances in gene sequencing also could help medical professionals discover more personalized care for patients leading to improved outcomes. A key goal of precision medicine.
One of the conclusions to be drawn from this work is that clinical laboratories and anatomic pathology groups will need to be able to handle immense amounts of data, while at the same time having the capabilities to analyze that data and identify useful patterns that can help diagnose patients earlier and more accurately.
