All-of-Us program is free to participants and provides data to more than 800 research studies for cancer, COVID-19, Alzheimer’s, and other diseases; findings will lead to new biomarkers for clinical laboratory tests
It is hard to say no to free. At least that is what the National Institutes of Health (NIH) is counting on to help increase the size and diversity of its database of genetic sequences. The NIH’s All-of-Us Research Program is offering free genetic testing for all participants in the program, as well as free wearable Fitbits for those selected to provide lifestyle and behavior data.
Many pathologists and clinical laboratory managers know that this group of researchers hope to build a database of more than one million genetic sequences to better understand “how certain genetic traits affect underrepresented communities, which could greatly affect the future of customized healthcare,” CBS affiliate 8 News Now reported.
“Customized healthcare” is a euphemism for precision medicine, and genetic sequencing is increasingly playing a key role in the development of personalized diagnostics and therapeutics for cancer and other deadly diseases.
In “VA’s ‘Million Veterans Program’ Research Study Receives Its 100,000th Human Genome Sequence,” Dark Daily described how the NIH’s All-of-Us program was launched in 2018 to aid research into health outcomes influenced by genetics, environments, and lifestyle. At that time, the program had biological samples from more than 270,000 people with a goal of one million participants.
Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research in La Jolla, Calif., joined the All-of-Us program after losing a family member “to a condition I believe could have been managed with changes to their lifestyle,” he told 8 News Now.
“What we are building will empower researchers with the information needed to make such conclusions (about possible need to change lifestyles) and forever alter how diseases are treated,” he added. “I hope that what we are doing here will help my son grow up in a world where healthcare is more of a priority, and many of the ailments we see today are things of the past.”
Such genetic testing could discover biomarkers for future personalized clinical laboratory diagnostics and drug therapies, a key aspect of precision medicine.
The photo above shows an All-of-Us participant being prepped to provide a biological sample for genetic testing. According to Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research, “participants can provide as much or as little information as they like, every single data point matters.” The collected data is shared anonymously with more than 800 research studies for COVID-19, Alzheimer’s, cancer, and other diseases, 8 News Now reported. (Photo copyright: KLAS-TV.)
Scripps Research Integrates Mobile Health Technology into All-of-Us Program
A critical aspect of the NIH’s research is determining how people’s behavior combined with their genetics may predispose them to certain diseases. Nonprofit research institution Scripps Research is working with the NIH’s All of Us Research Program to enroll and collect biological samples from one million US residents.
In addition, Scripps is fitting study participants with wearable mobile health devices to capture data on their habits and lifestyles.
“Until now, the treatment and prevention of disease has been based on a ‘one-size-fits-all’ approach, with most therapeutics tailored for the ‘average patient’. However, advances in genomic sequencing, mobile health technologies, and increasingly sophisticated informatics are ushering in a new era of precision medicine. This new approach takes into account differences in people’s genes, environment, and lifestyles giving medical professionals resources to design targeted treatments and prevention strategies for the individual,” Scripps states on its website.
Can wearable fitness devices and related data contribute to research on genetics and healthcare outcomes? Scripps aims to find out. It has fitted 10,000 people in the All-of-Us program with Fitbit devices (Fitbit Charge 4 tracker or Fitbit Versa 3 smartwatch) at no cost. Since February, Scripps has distributed 10,000 Fitbit wearable devices through the All-of-Us program.
“By sharing information about their health, habits, and environment, participants will help researchers understand why people get sick or stay healthy,” the Scripps website adds.
The Scripps researchers plan to analyze how the people use the wearable devices. They are also accumulating data about participants’ physical activity, heart rate, sleep, and other health metrics and outcomes “as part of the broader All of Us program,” a Scripps news release explained.
“This is the first time All of Us is distributing devices to participants. Our goal is to better understand how participants engage during research studies in order to continually improve user experience and participation. We also expect to learn more about how wearable data may inform the personalization of healthcare,” said Julia Moore Vogel, PhD, Director of The Participant Center at the All of Us Research Program at Scripps Research, in the news release.
All-of-Us Program Records ‘Significant Progress in Participant Diversity’
As of June, the NIH has enrolled 386,000 participants into the All-of-Us program, with 278,000 consenting to all of the program’s steps. Eighty percent of biological samples in the collection are from people in communities that have been under-represented in previous biomedical research an NIH new release noted. According to the NIH, that gives the All-of-Us research program “the most diverse dataset.”
What will all this research ultimately bring to clinical laboratories? Who knows? Nevertheless, if federal institutions like the NIH and non-profit research companies like Scripps believe precision medicine is worth investing in, then the All-of-Us program is worth watching.
A diverse database of a million genetic sequences combined with lifestyle and behavioral data may lead to new and improved personalized diagnostics and drug therapies.
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.
Studies into use of population-level genomic cancer screening show promising results while indicating that such testing to find evidence of increased cancer risk among non-symptomatic people may be beneficial
In another example of a government health system initiating a program designed to proactively identify people at risk for a serious disease to allow early clinical laboratory diagnosis and monitoring for the disease, cancer researchers at Monash University in Australia have receive a $2.97 million grant from the Medical Research Future Fund (MRFF) to study ways to “identifying people who are living with a heightened cancer risk who would ordinarily be informed only after a potentially incurable cancer is diagnosed.”
According to a Monash news release, the researchers, led by Associate Professor Paul Lacaze, PhD, Head of the Public Health Genomics Program at Monash University, plan to use the award to develop a “new low-cost DNA screening test which will be offered to 10,000 young Australians. The new approach, once scaled-up, has the potential to drastically improve access to preventive genetic testing in Australia, and could help make Australia the world’s first nation to offer preventive DNA screening through a public healthcare system.”
Called DNACancerScreen, the clinical genetic test will be offered to anyone between the ages of 18 and 40, rather than to a select group of people who have a family history of cancer or who present with symptoms. The Monash scientists hope to advance knowledge about the relationship of specific genes and how they cause or contribute to cancer. Such information, they believe, could lead to the development of new precision medicine diagnostic tests and anti-cancer drug therapies.
Gap in Current Cancer Screening Practices
The DNACancerScreen test will look for genes related to two specific cancer categories:
Hereditary Breast and Ovarian Cancer Syndrome is associated with an increased risk of developing breast, ovarian, prostate, and pancreatic cancers, as well as melanoma. Lynch Syndrome is associated with colorectal, endometrial, ovarian, and other cancers.
Currently, screening practices may miss as many as 50-90% of individuals who carry genetic mutations associated with hereditary breast and ovarian cancer, and as many as 95% of those at risk due to Lynch Syndrome, according to the Monash news release.
But currently, only those with a family history of these cancers, or those who present with symptoms, are screened. By targeting younger individuals for screening, Lacaze and his team hope to give those at risk a better chance at early detection.
“This will empower young Australians to take proactive steps to mitigate risk, for earlier detection, surveillance from a younger age, and prevention of cancer altogether,” Lacaze said in the news release.
Along with the possibility of saving lives, Associate Professor Paul Lacaze, PhD (above), Head of the Public Health Genomics Program at Monash University, expects that the screening program will have an economic impact as well. “This type of preventive DNA testing will not only save lives, but also save the Australian public healthcare system money by preventing thousands of cancers,” he said. There’s evidence to back up his statement. In 2019 he led a team that published a study, titled, “Population Genomic Screening of All Young Adults in a Healthcare System: A Cost Effectiveness Analysis.” That study concluded, “Preventive genomic screening in early adulthood would be highly cost-effective in a single-payer healthcare system, but ethical issues must be considered.” (Photo copyright: Monash University.)
Similar Genetic Studies Show Encouraging Results
Although the DNACancerScreen study in Australia is important, it is not the first to consider the impact of population-level screening for Tier 1 genetic mutations. The Healthy Nevada Project (HVN), a project that combined genetic, clinical, environmental, and social data, tested participants for those Tier 1 conditions. The project was launched in 2016 and currently has more than 50,000 participants, a Desert Research Institute (DRI) press release noted.
In 2018, HVN began informing participants who had increased risk for hereditary breast and ovarian cancer, Lynch Syndrome, and a third condition called Familial Hypercholesterolemia. There were 27,000 participants, and 90% of those who had genetic mutations associated with the three Tier 1 conditions had not been previously identified.
“Our first goal was to deliver actionable health data back to the participants of the study and understand whether or not broad population screening of CDC Tier 1 genomic conditions was a practical tool to identify at-risk individuals,” said Joseph Grzymski, PhD, lead author of the HVN study in the DRI press release.
Grzymski is Principal Investigator of the Healthy Nevada Project, Director of the Renown Institute for Health Innovation, Chief Scientific Officer for Renown Health, and a Research Professor in Computational Biology and Genetics at the Desert Research Institute.
“Now, two years into doing that it is clear that the clinical guidelines for detecting risk in individuals are too narrow and miss too many at risk individuals,” he added.
A total of 358, or 1.33% of the 26,906 participants in the Healthy Nevada Project were carriers for the Tier 1 conditions, but only 25% of them met the current guidelines for screening, and only 22 had any previous suspicion in their medical records of their genetic conditions.
Another project, the MyCode Community Health Initiative conducted at Geisinger Health System, found that 87% of participants with a Tier 1 gene variant did not have a prior diagnosis of a related condition. When the participants were notified of their increased risk, 70% chose to have a related, suggested procedure.
“This evidence suggests that genomic screening programs are an effective way to identify individuals who could benefit from early intervention and risk management—but [who] have not yet been diagnosed—and encourage these individuals to take measures to reduce their risk,” a Geisinger Health press release noted.
Realizing the Promise of Precision Medicine
Studies like these are an important step in realizing the potential of precision medicine in practical terms. The Tier 1 genetic conditions are just a few of the more than 22,000 recognized human genes of which scientists have a clear understanding. Focusing only on those few genetic conditions enables clinicians to better help patients decide how to manage their risk.
“Genomic screening can identify at-risk individuals more comprehensively than previous methods and start people on the path to managing that risk. The next step is figuring out the impact genomic screening has on improving population health,” said Adam Buchanan, MPH, MS, Director of Geisinger’s Genomic Medicine Institute.
These are positive developments for clinical laboratories and anatomic pathology group practices. The three examples cited above show that a proactive screening program using genetic tests can identify individuals at higher risk for certain cancers. Funding such programs will be the challenge.
At the current cost of genetic testing, screening 100 people to identify a few individuals at high risk for cancer would probably not be considered the highest and best use of the limited funds available to the healthcare system.
Advancements in genetic sequencing continue to enable microbiologists and genetic scientists to explore the origins and mutations of deadly diseases
Microbiologists and researchers can now study the gene sequence of 5,000-year-old bubonic plague bacteria. The scientific team that achieved this feat of gene sequencing believes this is the oldest case of the ancient strain of the plague found to date.
For microbiologists, this demonstrates how advances in gene sequencing technologies are allowing scientists to go further back in time to look at how the genomes of bacteria and viruses have evolved and mutated. This helps science understand the process of genetic mutation, as well as learning which mutations survived because they could more easily infect humans.
Missing Gene has ‘Dramatic Influence on Virulence’ of Plague
To conduct their study, the researchers sequenced the genomes of samples from the teeth and bones of four hunter-gatherers and tested the remains for bacterial and viral pathogens. They found evidence of Yersinia pestis (Y. pestis) in the dental remains of a 20- to 30-year-old male dubbed RV 2039.
The jaw bones used for the research were discovered in the late 1800s in the Rinnukalns, a stone age settlement unearthed in present-day Republic of Latvia in the late 19th century.
Missing Genetic Element in Ancient Bacterium
The scientists were surprised to find evidence of Y. pestis in the remains and noted that the analysis of the microbe lacked a crucial genetic element observed in later strains of the bacteria. Missing was the gene that allows biting fleas to act as vectors to spread the plague to humans.
“What’s so surprising is that we see already in this early strain more or less the complete genetic set of Y. pestis, and only a few genes are lacking,” said biochemist and archeologist Ben Krause-Kyora, Professor and head of the Ancient DNA (aDNA) Laboratory at the University of Kiel in Germany, and one of the authors of the study, in a press release.
“But even a small shift in genetic settings can have a dramatic influence on virulence,” he added.
This absent gene also is responsible for creating the pus-filled buboes associated with the Black Death (bubonic plague) that occurred in the 1300s. The Black Death killed 75 million to 200 million people worldwide, mostly in Eurasia and North Africa. It is to date the most fatal pandemic recorded in human history.
“Different pathogens and the human genome have always evolved together,” said Professor Ben Krause-Kyora (above left with and Steve Zäuner at center and Dr. Silvia Codreanu-Windauer at right), in the press release. “We know Y. pestis most likely killed half of the European population in a short time frame, so it should have a big impact on the human genome. But even before that, we see major turnover in our immune genes at the end of the Neolithic Age, and it could be that we were seeing a significant change in the pathogen landscape at that time as well,” he added. (Photo copyright: Mittelbayerische.)
A Less Lethal Bubonic Plague?
Although RV 2039 most likely perished from the bubonic plague, the researchers believe his strain of the infection was more mild, less contagious, and not as lethal as the later genetic mutations of the bacteria that caused the Black Death pandemic. The researchers concluded that the man most likely contracted the disease through a bite from an infected rodent or other animal, the press release notes.
“Isolated cases of transmission from animals to people could explain the different social environments where these ancient diseased humans are discovered,” Krause-Kyora said in the press release. “We see it in societies that are herders in the steppe, hunter-gatherers who are fishing, and in farmer communities—totally different social settings but always spontaneous occurrence of Y. pestis cases.”
From Animal Bite to Flea Infection in 7,000 Years’ Worth of Mutations
The Y. pestis bacteria that infected RV 2039, the researchers surmised, most likely split from its predecessor, Yersinia pseudotuberculosis, which first appeared on Earth about 7,000 years ago. It most likely took Y. pestis over a thousand years to acquire all the mutations necessary for flea-based transmission of the bacteria to humans, the researchers noted.
“What’s most astonishing is that we can push back the appearance of Y. pestis 2,000 years farther than previously published studies suggested,” Krause-Kyora said. “It seems that we are really close to the origin of the bacteria.”
It is unknown how many cases still occur worldwide due to unreliable diagnoses and poor reporting in developing countries. However, data from the World Health Organization (WHO) states that there were 3,248 cases of plague reported worldwide between 2010 and 2015, including 584 deaths. Currently, the three most endemic countries for plague are the Democratic Republic of the Congo, Madagascar, and Peru.
The researchers’ findings illustrate how advances in gene sequencing technologies are helping microbiologists, virologists, and genetic scientists understand the affect mutations have on diseases that have plagued humans since the beginning of humanity itself.
Will this lead to new genomic diagnostics? Perhaps. The research is worth watching.
Microbiologists will want to take note of the CDC’s statement that the illness can masquerade as other diseases
It is the latest example of a bacterium uncommon in the United States that has infected patients in this country—one of whom has died. The three infected patients live in separate states, but genetic analysis indicates their cases may be related.
According to the health alert, “Based on genomic analysis, these three cases (one male, two females; two adults and one child) may share a potential common source of exposure. The first case, identified in March 2021, was fatal. Two other patients were identified in May 2021, one of whom is still hospitalized. One has been discharged to a transitional care unit. None of the patients’ families reported a history of traveling outside of the continental United States.”
The CDC warned, “Symptoms of melioidosis are varied and nonspecific and may include pneumonia, abscess formation, and/or blood infections. Due to its nonspecific symptoms, melioidosis can initially be mistaken for other diseases such as tuberculosis, and proper treatment may be delayed.”
Microbiology Laboratories Should Be on Alert
Melioidosis is typically only seen in subtropical and tropical regions and can be highly fatal. It is unknown how the trio of patients who contracted the illness became infected, but according to the CDC the cases do appear to be connected.
“Testing suggests a common source of infection, but that source has not yet been identified,” a CDC representative told Gizmodo. “CDC is working with states to assess exposures or products these individuals have in common, as well as environmental samples from the states where cases have been identified. Additionally, CDC experts are providing epidemiologic assistance to help investigate the cause of infection,” the CDC added.
“Melioidosis is a serious neglected tropical disease of Southeast Asia, India, and Australia where it is a major cause of pneumonia, abscesses, and sepsis. The fact that it may be gaining a foothold in the US is concerning,” pediatrician Peter Hotez, MD, PhD (above), Dean of the National School of Tropical Medicine, Professor of Pediatrics and Molecular Virology and Microbiology at Baylor College of Medicine, and Director of the Center for Vaccine Development at Texas Children’s Hospital, told Gizmodo. Clinical laboratories and microbiologists will want to monitor these cases for future developments. (Photo copyright: Baylor College of Medicine.)
Melioidosis, also called Whitmore’s disease, was first described by Alfred Whitmore, an English pathologist, in 1912 in what is now present-day Myanmar. The bacterium (Burkholderia pseudomallei) can be found in contaminated soil and water. It is predominately found in tropical climates in Southeast Asia and northern Australia and can affect humans and many species of animals.
Researchers believe the disease may be acquired through the inhalation of contaminated dust particles or water droplets, the ingestion of contaminated water or soil-contaminated food, or other contact with tainted soil, especially through skin abrasions. It is very rare to contract melioidosis from infected individuals.
Melioidosis Masquerades as Other Illnesses
The symptoms of melioidosis are wide-ranging and non-specific and can resemble those of other illnesses. In addition, there are several types of the illness, and they can each act differently depending on where the infection is in the body. The most common symptoms of melioidosis include:
Localized Infection:
Localized pain or swelling
Fever
Ulceration
Abscess
Pulmonary Infection:
Cough
Chest pain
High fever
Headache
Anorexia
Bloodstream Infection:
Fever
Headache
Respiratory distress
Abdominal discomfort
Joint pain
Disorientation
Disseminated Infection:
Fever
Weight loss
Stomach or chest pain
Muscle or joint pain
Headache
Central nervous system/brain infection
Seizures
According to the CDC, the time between an exposure to Burkholderia pseudomallei and the first emergence of Melioidosis symptoms is not clearly defined but could range from one day to many years. However, most infected individuals begin experiencing symptoms of melioidosis within two to four weeks after exposure.
Melioidosis is difficult to diagnose, and some automated bacterial reading instruments can mistake Burkholderia pseudomallei for other bacteria. It is estimated that the disease accounts for 89,000 deaths per year worldwide. Delays in diagnosis and treatment often lead to poor patient outcomes and the mortality rate can exceed 40% in some regions, Nature reported.
The illness is typically treated with appropriate drug therapies including intravenous antimicrobial medications, such as Ceftazidime or Meropenem, followed by an oral antimicrobial therapy such as Trimethoprim-sulfamethoxazole or Amoxicillin/Clavulanic Acid. It may take several months for a patient to be cured of melioidosis, depending on the extent of the infection.
Deadly Bacterium’s Countries of Origin and Spread to the US
According to CDC data, the greatest number of melioidosis cases are reported in Thailand, Malaysia, Singapore, and northern Australia. Cases also have been reported in other Asian countries as well as Mexico and Central America.
Burkholderia pseudomallei does not occur naturally in the US, and cases of melioidosis identified in the US are usually only seen in world travelers and immigrants who come from countries where the disease is widespread. The bacterium has been found in soil in Mexico, so it is possible that it could spread to parts of the US, which has led to concern among microbiologists.
“Due to changes in weather patterns, some pathogens that normally were not present in a particular area might start causing disease,” Alfredo Torres, PhD, Associate Provost, Department of Microbiology and Immunology, University of Texas Medical Branch, told Gizmodo. “Therefore, it is important to make the health professionals aware of this pathogen and the disease that it causes, so quick identification can be done, and treatment is properly used to save lives. Without that, it might be too late for the next melioidosis patient when the proper diagnosis is done.”
The CDC has suggested that healthcare workers consider melioidosis as a possible diagnosis for patients who have compatible symptoms, even if they have not recently traveled outside of the US.
CDC Suggests Rerunning Certain Clinical Laboratory Tests
Because Burkholderia pseudomallei can be mistaken for other bacteria, the CDC also urges the rerunning of clinical laboratory tests using automated identification, especially if another bacterium that is often mistaken for Burkholderia pseudomallei is present, Gizmodo noted.
“CDC encourages healthcare workers to be aware of the potential for more cases and to report cases to their state health departments,” the CDC stated.
The CDC considers the risk of melioidosis to the public in the US to be low, and that the chances of a potential outbreak are unlikely. However, the origins of these three cases remain a mystery and warrant further investigation.
Microbiologists and clinical laboratories should be aware of and remain alert about this potentially fatal illness. It is possible that more cases will arise in the future, especially in the three states where it has already been found.
Using algorithmic technology designed for mapping the stars, the scientists have created an imaging/spatial location platform called AstroPath which may help oncologists develop immunotherapies that work best on specific cancers. Such a capability is key to effective precision medicine techniques.
Dark Daily has regularly pointed out that technologies developed in other fields of science will eventually be brought into anatomic pathology and clinical laboratory medicine. Use of the star-mapping technology in oncology and the diagnosis of cancer is one such example.
In “Analysis of Multispectral Imaging with the AstroPath Platform Informs Efficacy of PD-1 Blockade,” published in the journal Science, the multi-institution research team wrote, “Here, we present the AstroPath platform, an end-to-end pathology workflow with rigorous quality control for creating quantitative, spatially resolved mIF [multiplex immunofluorescence] datasets. Although the current effort focused on a six-plex mIF assay, the principles described here provide a general framework for the development of any multiplex assay with single-cell image resolution. Such approaches will vastly improve the standardization and scalability of these technologies, enabling cross-site and cross-study comparisons. This will be essential for multiplex imaging technologies to realize their potential as biomarker discovery platforms and ultimately as standard diagnostic tests for clinical therapeutic decision-making.
“Drawing from the field of astronomy, in which petabytes of imaging data are routinely analyzed across a wide spectral range, [the researchers] developed a platform for multispectral imaging of whole-tumor sections with high-fidelity single-cell resolution. The resultant AstroPath platform was used to develop a multiplex immunofluorescent assay highly predictive of responses and outcomes for melanoma patients receiving immunotherapy,” the researchers added.
Using Star Mapping Software to Fight Cancer
“The application of advanced mapping techniques from astronomy has the potential to identify predictive biomarkers that will help physicians design precise immunotherapy treatments for individual cancer patients,” said Michele Cleary, PhD, CEO of the Mark Foundation for Cancer Research, in a Johns Hopkins news release.
Although the universe we live in and the universe of a cancerous tumor may not seem related, the fact is the same visualization technology can be used to map them both.
“What should be pointed out is that astronomy is mapping the sky in three dimensions, so keeping the spatial relationships while also identify each heavenly body is the goal of these algorithms,” said Robert Michel, Publisher and Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
“Both aspects of that information technology have value in surgical pathology, where the spatial relationship of different cells and cell structures is relevant and important while also having the ability to identify and characterize different types of cells and cell structures. This technology appears to also be capable of identifying multiple biomarkers,” he added.
The image above, taken from the researchers’ Science paper, illustrates the “strong parallels between multispectral analyses in astronomy and emerging multiplexing platforms for pathology.” The researchers wrote, “the next generation of tissue-based biomarkers are likely to be identified by use of large, well-curated datasets. To that end, image analysis approaches originally developed for astronomy were applied to pathology specimens to produce trillions of pixels of robust tissue imaging data and facilitate assay and atlas development.” Anatomic pathologists may be direct recipients of new cancer diagnostic tools based on the AstroPath platform. (Photo copyrights: Johns Hopkins University/Mark Foundation Center for Advanced Genomics/Bloomberg-Kimmel Institute.)
AstroPath Provides 1,000 Times the Information Content from A Single Biopsy
According to the news release, “[The researchers] characterized the immune microenvironment in melanoma biopsies by examining the immune cells in and around the cancer cells within the tumor mass and then identified a composite biomarker that includes six markers and is highly predictive of response to a specific type of an immunotherapy called Anti-PD-1 therapy.”
This is where the use of AstroPath is truly innovative. Previously, researchers could only identify those biomarkers one at a time, through a painstaking process.
“For the last 40 years, pathology analysis of cancer has examined one marker at a time, which provides limited information,” said Drew Pardoll, MD, PhD, Director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy and a Johns Hopkins professor of oncology, in the news release. “Leveraging new technology, including instrumentation to image up to 12 markers simultaneously, the AstroPath imaging algorithms provide 1,000 times the information content from a single biopsy than is currently available through routine pathology,” he added.
More information about a cancerous tumor means clinicians have more tools to combat it. Treatment becomes less about finding the right immunotherapy and more about treating it immediately.
“This facilitates precision cancer immunotherapy—identifying the unique features of each patient’s cancer to predict who will respond to a given immunotherapy, such as anti-PD-1, and who will not. In doing so, it also advances diagnostic pathology from uniparameter to multiparameter assays,” Pardoll said.
Big Data and Data Analysis Is the Future of Precision Medicine
The use of data in science is changing how researchers, clinicians, pathologists, and others provide healthcare in the modern world. When it is properly collected and analyzed, data holds the key to precision medicine’s personalized and targeted patient care.
“Big data is changing science. There are applications everywhere, from astronomy to genomics to oceanography,” said Alexander S. Szalay, PhD, Bloomberg Distinguished Professor and Professor in the Department of Computer Science at Johns Hopkins University, and Director of the Institute for Data Intensive Engineering and Science (IDIES), in the news release.
“Data-intensive scientific discovery is a new paradigm. The technical challenge we face is how to get consistent, reproducible results when you collect data at scale. AstroPath is a step towards establishing a universal standard,” he added.
Should AstroPath prove to be a clinically safe and accurate method for developing precision medicine cancer therapies, anatomic pathologists can look forward to exciting new ways to diagnose cancer and determine the best courses of treatment based on each patient’s unique medical needs.
