GISAID hosts a vast, open database of genomic sequences of SARS-CoV-2 coronavirus samples, and medical laboratory scientists in countries across the globe are contributing
Clinical laboratories around the world have been contributing to the global scientific community’s database of knowledge about SARS-CoV-2, the coronavirus that caused the COVID-19 pandemic, and its variants, through an ingenious and crucial network known as GISAID. This cooperative sharing of the coronavirus’ genetic data (now four million genomic sequences strong) has greatly contributed to understanding the spread of infections and progress obtained in developing effective treatments and vaccines.
Headquartered in Munich, Germany, GISAID, which stands for Global Initiative on Sharing Avian Influenza Data, was created in 2008 during the Avian Influenza (Bird Flu) pandemic. The GISAID initiative promotes “the rapid sharing of data from all influenza viruses and the coronavirus causing COVID-19. This includes genetic sequence and related clinical and epidemiological data associated with human viruses, and geographical as well as species-specific data associated with avian and other animal viruses, to help researchers understand how viruses evolve and spread during epidemics and pandemics,” according to the GISAID website.
Clinical pathologists are likely familiar with GISAID. The initiative has become an indispensable tool for researchers battling SARS-CoV-2. GISAID allows scientists and organizations worldwide to upload genetic sequences of COVID-19 samples. Those sequences can then be used in research for treatments, vaccines, and to track emerging variants. The information is invaluable, freely available, and represents the collaborative efforts of scientists around the world in the fight against COVID-19 and other infectious diseases.
An article published in The World, titled, “From Congo to Chile, Small Labs Are Playing a Growing Role in Global Understanding of COVID,” noted that more than four million genomic sequences have been submitted as of October 15, 2021. The more countries around the world that submit sequences to GISAID, the more understanding scientists have of how the virus is mutating. And, as the cost of performing genomic sequencing declines, the number of countries submitting genomes of SARS-CoV-2 to GISAID is rising.
How GISAID Ensures Contributors Receive Credit for Their Work
One of the reasons that GISAID has been so successful in gathering data is that it requires anyone who uses data downloaded from the massive database to give credit to the person or organization who uploaded it. In other words, if a scientist in the United Kingdom (UK) does breakthrough research using genomes that were originally uploaded to GISAID by a scientist in the Congo, the UK scientist must credit the work of the scientist from the Congo.
Other genomic databases do not have this requirement and genetic researchers are often hesitant to share information due to fear their work will be co-opted by others. According to The World, scientists in lower income countries are particularly vulnerable to having their work appropriated.
Even worse is having one’s work appropriated, used to create a product, and then not being given access to that product.
“Unfortunately, we’ve seen also the situation whereby people have leveraged that data and created the solution and refused to share the solution with those that shared the data,” virologist Christian Happi, PhD (above), who directs the African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer’s University in Nigeria, told The World. “And that is definitely going to roll back this whole open data sharing and access principle.” Happi is also a Visiting Scientist in the Department of Immunology and Infectious Diseases at Harvard’s T.H. Chan School of Public Health. (Photo copyright: Pius Utomi Ekpei/AFP/News 24.)
That is why GISAID’s policy of giving credit is so important, as molecular biologist Francine Ntoumi, PhD, told The World. “This means that we are going to participate in the game. We are able to say what is circulating. You are no more an observer and I think it makes a difference.” Ntoumi is Founder and Executive Director of the Congolese Foundation for Medical Research (CFMR) in the Republic of Congo, a lecturer in Immunology at Marien Ngouabi University, and Associate Professor and Head of a Research Group at the Institute of Tropical Medicine at the University of Tübingen, Germany.
The guarantee that credit will be given softens some of those fears and explains why the GISAID database is so vast, and increasingly contains sequences from scientists in Africa, South American, and other places where genomic sequencing was not widespread prior to the pandemic. Information from all over the world is crucial for scientists monitoring the mutations of the SARS-CoV-2 coronavirus.
Criticisms of GISAID
The fact that more countries are contributing to the GISAID database is certainly a positive, but the non-profit is not without its critics. There have been complaints about the lack of transparency, and some researchers claim to have had their access denied to the data without any explanation.
An article published in Science reported that “Scientists live in fear of losing access to the GISAID database.”
One scientist who requested anonymity told Science, “I am so tired of being scared all the time, of being terrified that if I take a step wrong, I will lose access to the data that I base my research on. [GISAID] has that sword hanging over any scientist that works on SARS-CoV-2.”
In response to these criticisms, GISAID said in a statement, “Any individual who registers with GISAID and agrees to the GISAID terms of use will be granted access credentials. … On rare occasions, GISAID has found it necessary to temporarily suspend access credentials to protect the GISAID sharing mechanism,” The World reported.
The strict sharing rules may be necessary to encourage researchers in lower income countries to contribute their genomic data on SARS-CoV-2. Charles Rotimi, PhD, a geneticist at the National Human Genome Research Institute (NHGRI), told Science, “To make scientists, especially from developing countries, more comfortable—making sure that they are recognized in the work that they are doing—sometimes you have to create an extra layer [of protection].”
GISAID has certainly accomplished much in its assembling four million SARS-CoV-2 genetic sequences. The initiative’s efforts have contributed to a substantial increase in the number of countries around the world that now have gene sequencing capabilities.
This is another illustration for clinical laboratory managers and pathologists of how continual technology advances in gene sequencing equipment and data analysis software make it significantly cheaper, faster, and more accurate to do genetic sequencing. This was not true, just a few years ago.
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.
Recent research into transposons within DNA dark matter may produce new biomarkers for clinical laboratory testing and diagnostics
There’s been another interesting development in the study of genetic “dark matter” which may give rise to new biomarkers for clinical laboratory diagnostics and testing. This is worth noting, because biological dark matter has long been considered non-critical and immaterial to the human organism or human evolution. Researchers often refer to it as junk DNA.
However, newly-released research suggests that transposons (aka, transposable elements) contained within our genetic dark matter may play a “critical role in mammalian development,” according to a UC Berkeley news release. Transposons, the release notes, are “viral elements [that] have invaded mammalian genomes for millions of years and currently make up nearly half the DNA in the genomes of all living mammals.”
The study, led by researchers at the University of California, Berkeley, and Washington University in St. Louis, found at least one family of transposons that affected the viability of test mice. They believe the transposon could play a similar role in all mammals—including humans.
Molecular biologist Lin He, PhD (above), led the study conducted at the University of California, Berkeley, and Washington University in St. Louis, which found that bits of DNA once considered “junk” may actually perform important functions, such as ensuring fertility. These findings may one day confirm new biomarkers for clinical laboratory testing. (Photo copyright: MacArthur Foundation.)
How Removal of a Transposon Led to Death
The researchers found that the function of one type of transposon affected whether a mouse fetus could form properly and survive birth. The transposon “regulates the proliferation of cells in the early fertilized embryo and the timing of implantation in the mother’s uterus,” the news release notes.
To perform the research, the scientists removed a specific transposon that controls the proliferation of cells in the early fertilization of an embryo from the mice. After extracting that transposon, half of the mouse pups died before birth.
The researchers then looked at other mammalian species—including humans—and “found virus-derived regulatory elements linked to cell proliferation and timing of embryo implantation, suggesting that ancient viral DNA has been domesticated independently to play a crucial role in early embryonic development in all mammals,” UC Berkeley noted.
The researchers suggest that some of our dark matter DNA has an important function in our embryonic maturation and survival.
“The mouse and humans share 99% of their protein coding genes in their genomes—we are very similar with each other,” said molecular biologist and senior author of the study Lin He, PhD, Associate Professor, Department of Molecular and Cell Biology, UC Berkeley, in the news release.
“So, what constitutes the differences between mice and humans? One of the major differences is gene regulation—mice and humans have the same genes, but they can be regulated differently. Transposons have the capacity to generate a lot of gene regulatory diversity and could help us to understand species-specific differences in the world.”
“The real significance of this story is it tells us how evolution works in the most unexpected manner possible,” said geneticist and study co-author Ting Wang, PhD, Sanford and Karen Loewentheil Distinguished Professor of Medicine, Department of Genetics, Washington University School of Medicine, in the UC Berkeley news release.
“Transposons were long considered useless genetic material, but they make up such a big portion of the mammalian genome. A lot of interesting studies illustrate that transposons are a driving force of human genome evolution. Yet, this is the first example that I know of where deletion of a piece of junk DNA leads to a lethal phenotype, demonstrating that the function of specific transposons can be essential,” he added.
Their research could have implications for human fertility as many miscarriages in humans are due to undiagnosed conditions or have no apparent genetic component.
“If 50% of our genome is non-coding or repetitive—this dark matter—it is very tempting to ask the question whether or not human reproduction and the causes of human infertility can be explained by junk DNA sequences,” he said.
Thus, the UC Berkeley/Washington University study is building on prior research demonstrating that dark matter DNA may not be “junk” after all. More specifically, transposons may eventually have value as biomarkers for clinical laboratory tests and diagnostics.
Of course, additional research and studies are needed to validate these findings and provide greater knowledge about the function of specific transposons. But it’s an intriguing development that’s worth following.
Several young companies hope to expand the direct-to-consumer test market by introducing new diagnostic tests to serve the women’s health market
Providing women with at-home lab test kits is the goal of a growing class of start-up companies that are bringing to market consumer test kits for a range of health conditions common to women. These companies believe they can shift a substantial volume of such testing away from the nation’s medical laboratories.
Moreover, diagnostic startups that develop at-home direct-to-consumer (DTC) clinical laboratory genetic tests have been hot commodities among venture capitalists and other healthcare investors willing to put tens of millions of dollars into these new firms. The New York Times observed that, until recently, women’s healthcare needs have rarely been the focus of new diagnostic testing companies, but that the situation may be changing.
“Femtech” (short for female technology) products and services that address the health and wellness needs of women is the new buzz word in healthcare. It describes female-focused diagnostic startups aiming at vaginal health and other medical issues that go beyond reproductive health concerns.
This, however, is a dual-edged sword for clinical laboratory leaders. Growth in this segment could lead to new diagnostics tests that boost a medical lab’s bottom line or, conversely, it could reduce revenue as patients self-diagnose urinary tract infections (UTIs), yeast infections, and other conditions through at-home DTC testing.
“The market potential is huge,” Michelle Tempest, MD (above), a partner at the London-based healthcare consulting firm Candesic, told The New York Times. “There’s definitely an increasing appetite for anything in the world which is technology and a realization that female consumer power has arrived—and that it’s arrived in healthcare.” Tempest maintains the women’s health marketplace is ripe for growth, which could mean a boon for clinical laboratory testing and diagnostics designed specifically for women. (Photo copyright: Candesic.)
Vaginal Microbiome At-home Clinical Laboratory Tests in High Demand
One area in particular drawing the attention of several female-led startups is vaginal health. According to an article in Vogue, test developers Juno Bio and Evvy are leading the way with at-home vaginal microbiome tests that let users “know what’s up down there.”
New York City-based Evvy ($129 for a single test or $99 each for four tests per year) uses metagenomic sequencing to identify the bacteria and fungi present in the vaginal microbiome. This information helps customers to understand their levels of protective and disruptive bacteria, which can be associated with everything from reoccurring infections and transmission of sexually transmitted diseases to infertility.
London-based Juno Bio ($149 per test) does not disclose its testing method. It does, however, provide users with a “full vaginal microbiome profile.” The profile is accessed online within a “few days” of returning the vaginal swab sample to the company’s clinical laboratory.
Both companies note that their tests are intended to be used for wellness purposes and are not meant to diagnose or treat disease or substitute for a physician’s consultation.
Gynecologist Oluwatosin Goje, MD, MSCR, FACOG, a reproductive infectious disease specialist at Cleveland Clinic, believes the availability of at-home vaginal microbiome testing will provide valuable information to both women and their doctors.
“It’s a powerful tool because it enables us to look at the entire microbial community through metagenomics and decipher how the overall composition might be affecting symptoms and infections, as well as determine the best treatment pathway,” Goje, an Evvy Medical Advisor, told Vogue. “Understanding the complete vaginal microbiome allows us to be good antibiotic stewards and only administer antibiotics when needed. Patients can also retest remotely to understand how antibiotics and other treatments impacted their vaginal microbiome.”
Evvy, which offers women an at-home vaginal microbiome test (above) that can provide insights into chronic vaginal infections and proclivity to contract sexually transmitted diseases and other women’s health issues, is one of several women-led diagnostic start-ups focused on women’s health. (Photo copyright: Evvy.)
Removing the Discomfort of Shopping for Women’s Health Products
Jamie Norwood and Cynthia Plotch, co-founders of Stix, a supplier of women’s health products and education, launched their company with a product line of at-home pregnancy and ovulation tests. They have since expanded their offerings to include urinary tract infection (UTI) and yeast infection testing and treatments.
“You can test, relieve, treat, and help prevent future infections—all from the comfort of your own home,” Norwood, told Vogue. She emphasized that this is the kind of experience healthcare consumers are demanding in today’s ever-growing direct-to-consumer clinical laboratory testing landscape. “Agonizing over confusing over-the-counter products in the drugstore aisles, or bending over backwards to pick up a prescription at the pharmacy, just isn’t cutting it for Millennial and Gen Z consumers.”
According to WebMD, yeast infections are a chronic problem for many women. While 75% of women will get at least one yeast infection in their lifetime, up to 8% get more than four a year. In addition, the federal Centers for Disease Control and Prevention (CDC) points out that bacterial vaginosis is the most common vaginal condition in females ages 15-44.
Lola Priego, is CEO and founder of blood test company Base, which sells at-home saliva and finger-prick blood tests to monitor hormone levels, vitamin levels, neurotransmitters, and blood cell markers to improve everything from sleep and diet to sex drive. She predicts direct-to-consumer testing will become as common as fitness watches.
“Eventually, at-home lab testing will be another readily-used tool, similar to your health-tracking wearables, that helps us optimize for a well-rounded healthy lifestyle in a more individualized way,” Priego told Vogue.
Femtech a ‘Significantly Underdeveloped’ Market
In its latest Analyst Note, financial data firm PitchBook maintained that the market for female health products is poised for growth. TechCrunch, which reviewed PitchBook’s analysis of female-focused health products, reported that Femtech remains a “significantly underdeveloped” slice of health-tech spending.
While women spend an estimated $500 billion annually on medical expenses, only 4% of research and development money is targeted at women’s health, PitchBook noted. In its analysis, Pitchbook predicted the global market for female-focused health products will reach $3 billion by the end of 2030. By comparison, that segment of the healthcare market totaled $820.6 million last year.
“While we still view Femtech as a niche industry, we believe secular drivers could help propel new growth opportunities in the space,” PitchBook analysts wrote. “These include the increasing representation of women in the venture-backed technology community, rising awareness and acceptance of women’s health issues, and the growing prevalence of infectious diseases among women in some countries in Africa and Asia.
“Furthermore, while the majority of Femtech products have traditionally focused on reproductive health, we believe new approaches to women’s health research will help open the door to new products and services,” they noted.
Clinical laboratory leaders will be wise to carefully watch the growth of at-home DTC tests and products targeted at female healthcare consumers since fewer trips to physicians’ offices may mean fewer test orders for local labs.
At the same time, the opportunity exists for innovative pathologists and lab managers to develop digital services that allow consumers who are self-testing to store their home-test results in the lab’s app. They can then receive relevant insights from clinical pathologists to help them fully understand the implications of the test results.
Citizens claiming racial diversity increased by 276% in the 2020 census, leading experts to wonder if racial diversity is increasing or if people are simply electing to identify as such and how this trend will affect healthcare
Once again, we see another unexpected consequence to expanded DNA testing done by consumers for their own interests and needs. As NPR recently reported in “The Census Has Revealed a More Multiracial US. One Reason? Cheaper DNA Tests,” the growing trend of ordering low-cost direct-to-consumer (DTC) genetic testing to identify cultural heritage (where a family came from) and genealogy (to connect with extant family members) has educated healthcare consumers more about their cultural roots.
Such knowledge, NPR speculates, is allowing people to complete their census survey with more accurate “heritage” classifications.
The last US census showed an interesting change compared to previous census surveys. More Americans identified themselves as racially diverse than in previous censuses. Scientists in multiple specialty areas—including demographics, sociology, genetics, and more—are asking why.
According to federal Census Bureau data, in the most recent census, people who identify as more than one race rose by 276%! Scientists are only just beginning to hypothesize the reasons for this increase, but three potential factors, NPR reported, have emerged:
More children are being born to parents who identify with racial groups that are different from one another.
People are reconsidering what they want the government to know about their identities, according to Duke University Press.
The increased incidence of DNA testing for cultural heritage may be an additional factor in the different ways people identified themselves during the census, driving its popularity, NPR noted. More people are purchasing at-home DNA tests to learn where their ancestors lived and came from, and their family’s genealogy.
“Exactly how big of an effect these tests had on census results is difficult to pin down,” NPR reported. “But many researchers agree that as the cost of at-home kits fell in recent years, they have helped shape an increasing share of the country’s ever-changing ideas about the social construct that is race.”
How the Census Alters Government Policy
Pew Research noted that, although only about 16% of Americans have taken an ancestry DNA test, the marketing efforts of “companies such as 23andMe and Ancestry.com, which operates the AncestryDNA service, should not be underestimated,” NPR reported. They have a wide reach, and those efforts could be impacting how people think about race and ethnic identity.
For most of human history, social experience and contemporary family history have been the drivers of how people identified themselves. However, low-cost DTC genetic testing may be changing that.
“The public has kind of taken in the notion that you can find out ‘who you are’ with a test that’s supposed to analyze your genes,” Jenifer Bratter, PhD (above), a Professor of Sociology at Rice University who studies multiracial identity, told NPR. “What that does for anyone who does work in racial identity and racial demography is cause us to think through how genetic ideas of race are in public circulation.” Desire by healthcare consumers to know their risk for chronic disease has already driven a marked increase in demand for low-cost DNA testing, which has also affected the types of test orders clinical laboratory are receiving from doctors. (Photo copyright: Rice University.)
One concern that sociologists and demographers have about this trend is that the US census is an important tool in policy, civil rights protections, and even how researchers measure things like healthcare access disparities.
“You’re going to have a lot more people who are not part of marginalized groups in terms of their social experiences claiming to be part of marginalized groups. When it comes to understanding discrimination or inequality, we’re going have very inaccurate estimates,” says Wendy Roth, PhD, Associate Professor of Sociology, University of Pennsylvania, told NPR.
They developed the “genetic options” theory, “to account for how genetic ancestry tests influence consumers’ ethnic and racial identities.” They wrote, “The rapid growth of genetic ancestry testing has brought concerns that these tests will transform consumers’ racial and ethnic identities, producing “geneticized” identities determined by genetic knowledge.”
However, a more healthcare-related motivation for taking a DTC DNA test is to learn about one’s potential risks for familial chronic health conditions, such as cancer, heart disease, and diabetes, etc.
“Whether that occurs through your primary care doctor, your large integrated health network, or your payor, I think there will be profound changes in society’s tolerance for using genetics for prevention,” he told GenomeWeb.
Regardless, as Dark Daily reported in 2020, sales of genetic tests from Ancestry and 23andMe show the market is cooling. Thus, with less than 20% of the population having taken DNA tests, and with sales slowing, genetics testing may not affect responses on the next US census, which is scheduled for April 1, 2030.
In the meantime, clinical laboratory managers should recognize how and why more consumers are interested in ordering their own medical laboratory tests and incorporate this trend into their lab’s strategic planning.
Newly combined digital pathology, artificial intelligence (AI), and omics technologies are providing anatomic pathologists and medical laboratory scientists with powerful diagnostic tools
Add “spatial transcriptomics” to the growing list of “omics” that have the potential to deliver biomarkers which can be used for earlier and more accurate diagnoses of diseases and health conditions. As with other types of omics, spatial transcriptomics might be a new tool for surgical pathologists once further studies support its use in clinical care.
Among this spectrum of omics is spatial transcriptomics, or ST for short.
Spatial Transcriptomics is a groundbreaking and powerful molecular profiling method used to measure all gene activity within a tissue sample. The technology is already leading to discoveries that are helping researchers gain valuable information about neurological diseases and breast cancer.
Marriage of Genetic Imaging and Sequencing
Spatial transcriptomics is a term used to describe a variety of methods designed to assign cell types that have been isolated and identified by messenger RNA (mRNA), to their locations in a histological section. The technology can determine subcellular localization of mRNA molecules and can quantify gene expression within anatomic pathology samples.
In “Spatial: The Next Omics Frontier,” Genetic Engineering and Biotechnology News (GEN) wrote, “Spatial transcriptomics gives a rich, spatial context to gene expression. By marrying imaging and sequencing, spatial transcriptomics can map where particular transcripts exist on the tissue, indicating where particular genes are expressed.”
In an interview with Technology Networks, George Emanuel, PhD, co-founder of life-science genomics company Vizgen, said, “Spatial transcriptomic profiling provides the genomic information of single cells as they are intricately spatially organized within their native tissue environment.
“With techniques such as single-cell sequencing, researchers can learn about cell type composition; however, these techniques isolate individual cells in droplets and do not preserve the tissue structure that is a fundamental component of every biological organism,” he added.
“Direct spatial profiling the cellular composition of the tissue allows you to better understand why certain cell types are observed there and how variations in cell state might be a consequence of the unique microenvironment within the tissue,” he continued. “In this way, spatial transcriptomics allows us to measure the complexity of biological systems along the axes that are most relevant to their function.”
“Although spatial genomics is a nascent field, we are already seeing broad interest among the community and excitement across a range of questions, all the way from plant biology to improving our understanding of the complex interactions of the tumor microenvironment,” George Emanuel, PhD (above), told Technology Networks. Oncologists, anatomic pathologists, and medical laboratory scientists my soon see diagnostics that take advantage of spatial genomics technologies. (Photo copyright: Vizgen.)
According to 10x Genomics, “spatial transcriptomics utilizes spotted arrays of specialized mRNA-capturing probes on the surface of glass slides. Each spot contains capture probes with a spatial barcode unique to that spot.
“When tissue is attached to the slide, the capture probes bind RNA from the adjacent point in the tissue. A reverse transcription reaction, while the tissue is still in place, generates a cDNA [complementary DNA] library that incorporates the spatial barcodes and preserves spatial information.
“Each spot contains approximately 200 million capture probes and all of the probes in an individual spot share a barcode that is specific to that spot.”
“The highly multiplexed transcriptomic readout reveals the complexity that arises from the very large number of genes in the genome, while high spatial resolution captures the exact locations where each transcript is being expressed,” Emanuel told Technology Networks.
Spatial Transcriptomics for Breast Cancer and Neurological Diagnostics
In that paper, the authors wrote “we envision that in the coming years we will see simplification, further standardization, and reduced pricing for the ST protocol leading to extensive ST sequencing of samples of various cancer types.”
Spatial transcriptomics is also being used to research neurological conditions and neurodegenerative diseases. ST has been proven as an effective tool to hunt for marker genes for these conditions as well as help medical professionals study drug therapies for the brain.
“You can actually map out where the target is in the brain, for example, and not only the approximate location inside the organ, but also in what type of cells,” Malte Kühnemund, PhD, Director of Research and Development at 10x Genomics, told Labiotech.eu. “You actually now know what type of cells you are targeting. That’s completely new information for them and it might help them to understand side effects and so on.”
The field of spatial transcriptomics is rapidly moving and changing as it branches out into more areas of healthcare. New discoveries within ST methodologies are making it possible to combine it with other technologies, such as Artificial Intelligence (AI), which could lead to powerful new ways oncologists and anatomic pathologists diagnose disease.
“I think it’s going to be tricky for pathologists to look at that data,” Kühnemund said. “I think this will go hand in hand with the digital pathology revolution where computers are doing the analysis and they spit out an answer. That’s a lot more precise than what any doctor could possibly do.”
Spatial transcriptomics certainly is a new and innovative way to look at tissue biology. However, the technology is still in its early stages and more research is needed to validate its development and results.
Nevertheless, this is an opportunity for companies developing artificial intelligence tools for analyzing digital pathology images to investigate how their AI technologies might be used with spatial transcriptomics to give anatomic pathologists a new and useful diagnostic tool.
