Oct 8, 2018 | Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Both health systems will use their EHRs to track genetic testing data and plan to bring genetic data to primary care physicians
Clinical laboratories and pathology groups face a big challenge in how to get appropriate genetic and molecular data into electronic health record (EHR) systems in ways that are helpful for physicians. Precision medicine faces many barriers and this is one of the biggest. Aside from the sheer enormity of the data, there’s the question of making it useful and accessible for patient care. Thus, when two major healthcare systems resolve to accomplish this with their EHRs, laboratory managers and pathologists should take notice.
NorthShore University HealthSystem in Illinois and Geisinger Health System in Pennsylvania and New Jersey are working to make genetic testing part of primary care. And both reached similar conclusions regarding the best way for primary care physicians to make use of the information.
One area of common interest is pharmacogenomics.
At NorthShore, two genetic testing programs—MedClueRx and the Genetic and Wellness Assessment—provide doctors with more information about how their patients metabolize certain drugs and whether or not their medical and family histories suggest they need further, more specific genetic testing.
“We’re not trying to make all of our primary care physicians into genomic experts. That is a difficult strategy that really isn’t scalable. But we’re giving them enough tools to help them feel comfortable,” Peter Hulick, MD, Director of the Center for Personalized Medicine at NorthShore, told Healthcare IT News.
Conversely, Geisinger has made genomic testing an automated part of primary care. When patients visit their primary care physicians, they are asked to sign a release and undergo whole genome sequencing. An article in For the Record describes Geisinger’s program:
“The American College of Medical Genetics and Genomics classifies 59 genes as clinically actionable, with an additional 21 others recommended by Geisinger. If a pathogenic or likely pathogenic variant is found in one of those 80 genes, the patient and the primary care provider are notified.”
William Andrew Faucett (left) is Director of Policy and Education, Office of the Chief Scientific Officer at Geisinger Health; and Peter Hulick, MD (right), is Director of the Center for Personalized Medicine at NorthShore University HealthSystem. Both are leading programs at their respective healthcare networks to improve precision medicine and primary care by including genetic testing data and accessibility to it in their patients’ EHRs. (Photo copyrights: Geisinger/NorthShore University HealthSystem.)
The EHR as the Way to Access Genetic Test Results
Both NorthShore and Geisinger selected their EHRs for making important genetic information accessible to primary care physicians, as well as an avenue for tracking that information over time.
Hulick told Healthcare IT News that NorthShore decided to make small changes to their existing Epic EHR that would enable seemingly simple but actually complex actions to take place. For example, tracking the results of a genetic test within the EHR. According to Hulick, making the genetic test results trackable creates a “variant repository,” also known as a Clinical Data Repository.
“Once you have that, you can start to link it to other information that’s known about the patient: family history status, etc.,” he explained. “And you can start to build an infrastructure around it and use some of the tools for clinical decision support that are used in other areas: drug/drug interactions, reminders for flu vaccinations, and you can start to build on those decision support tools but apply them to genomics.”
Like NorthShore, Geisinger is also using its EHR to make genetic testing information available to primary care physician when a problem variant is identified. They use EHR products from both Epic and Cerner and are working with both companies to streamline and simplify the processes related to genetic testing. When a potentially problematic variant is found, it is listed in the EHR’s problem list, similar to other health issues.
Geisinger has developed a reporting system called GenomeCOMPASS, which notifies patients of their results and provides related information. It also enables patients to connect with a geneticist. GenomeCOMPASS has a physician-facing side where primary care doctors receive the results and have access to more information.
Andrew Faucett, Senior Investigator (Professor) and Director of Policy and Education, Office of the Chief Scientific Officer at Geisinger, compares the interpretation of genetic testing to any other kind of medical testing. “If a patient gets an MRI, the primary care physicians doesn’t interpret it—the radiologist does,” adding, “Doctors want to help patients follow the recommendations of the experts,” he told For the Record.
The Unknown Factor
Even though researchers regularly make new discoveries in genomics, physicians practicing today have had little, if any, training on how to incorporate genetics into their patients’ care. Combine that lack of knowledge and training with the current lack of EHR interoperability and the challenges in using genetic testing for precision medicine multiply to a staggering degree.
One thing that is certain: the scientific community will continue to gather knowledge that can be applied to improving the health of patients. Medical pathology laboratories will play a critical role in both testing and helping ensure results are useful and accessible, now and in the future.
—Dava Stewart
Related Information:
Introducing “Genomics and Precision Health”
How NorthShore Tweaked Its Epic EHR to Put Precision Medicine into Routine Clinical Workflows
Precise, Purposeful Health Care
Next-Generation Laboratory Information Management Systems Will Deliver Medical Laboratory Test Results and Patient Data to Point of Care, Improving Outcomes, Efficiency, and Revenue
Jul 20, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Should greater attention be given to protein damage in chronic diseases such as Alzheimer’s and diabetes? One life scientist says “yes” and suggests changing how test developers view the cause of age-related and degenerative diseases
DNA and the human genome get plenty of media attention and are considered by many to be unlocking the secrets to health and long life. However, as clinical laboratory professionals know, DNA is just one component of the very complex organism that is a human being.
In fact, DNA, RNA, and proteins are all valid biomarkers for medical laboratory tests and, according to one life scientist, all three should get equal attention as to their role in curing disease and keeping people healthy.
Along with proteins and RNA, DNA is actually an “equal partner in the circle of life,” wrote David Grainger, PhD, CEO of Methuselah Health, in a Forbes opinion piece about what he calls the “cult of DNA-centricity” and its relative limitations.
Effects of Protein Damage
“Aging and age-related degenerative diseases are caused by protein damage rather than by DNA damage,” explained Grainger, a Life Scientist who studies the role proteins play in aging and disease. “DNA, like data, cannot by itself do anything. The data on your computer is powerless without apps to interpret it, screens and speakers to communicate it, keyboards and touchscreens to interact with it.”
“Similarly,” he continued, “the DNA sequence information (although it resides in a physical object—the DNA molecule—just as computer data resides on a hard disk) is powerless and ethereal until it is translated into proteins that can perform functions,” he points out.
According to Grainger, diseases such as cystic fibrosis and Duchenne Muscular Dystrophy may be associated with genetic mutation. However, other diseases take a different course and are more likely to develop due to protein damage, which he contends may strengthen in time, causing changes in cells or tissues and, eventually, age-related diseases.
“Alzheimer’s disease, diabetes, or autoimmunity often take decades to develop (even though your genome sequence has been the same since the day you were conceived); the insidious accumulation of the damaged protein may be very slow indeed,” he penned.
“But so strong is the cult of DNA-centricity that most scientists seem unwilling to challenge the fundamental assumption that the cause of late-onset diseases must lie somewhere in the genome,” Grainger concludes.
Shifting Focus from Genetics to Proteins
Besides being CEO of Methuselah Health, Grainger also is Co-Founder and Chief Scientific Advisor at Medicxi, a life sciences investment firm that backed Methuselah Health with $5 million in venture capital funding for research into disease treatments that focus on proteins in aging, reported Fierce CEO.
Methuselah Health, founded in 2015 in Cambridge, UK, with offices in the US, is reportedly using post-translational modifications for analysis of many different proteins.
“At Methuselah Health, we have shifted focus from the genetics—which tells you in an ideal world how your body would function—to the now: this is how your body functions now and this is what is going wrong with it. And that answer lies in the proteins,” stated Dr. David Grainger (above), CEO of Methuselah Health, in an interview with the UK’s New NHS Alliance. Click on this link to watch the full interview. [Photo and caption copyright: New NHS Alliance.]
This is how Methuselah Health analyzes damaged proteins using mass spectrometry, according to David Mosedale, PhD, Methuselah Health’s Chief Technology Officer, in the New NHS Alliance story:
- Protein samples from healthy individuals and people with diseases are used;
- Proteins from the samples are sliced into protein blocks and fed slowly into a mass spectrometer, which accurately weighs them;
- Scientists observe damage to individual blocks of proteins;
- Taking those blocks, proteins are reconstructed to ascertain which proteins have been damaged;
- Information is leveraged for discovery of drugs to target diseases.
Mass spectrometry is a powerful approach to protein sample identification, according to News-Medical.Net. It enables analysis of protein specificity and background contaminants. Interactions among proteins—with RNA or DNA—also are possible with mass spectrometry.
Methuselah Health’s scientists are particularly interested in the damaged proteins that have been around a while, which they call hyper-stable danger variants (HSDVs) and consider to be the foundation for development of age-related diseases, Grainger told WuXi AppTec.
“By applying the Methuselah platform, we can see the HSDVs and so understand which pathways we need to target to prevent disease,” he explained.
For clinical laboratories, pathologists, and their patients, work by Methuselah Health could accelerate the development of personalized medicine treatments for debilitating chronic diseases. Furthermore, it may compel more people to think of DNA as one of several components interacting that make up human bodies and not as the only game in diagnostics.
—Donna Marie Pocius
Related Information:
The Cult of DNA-Centricity
Methuselah Health CEO David Grainger Out to Aid Longevity
VIDEO: Methuselah Health, Addressing Diseases Associated with Aging
Understanding and Slowing the Human Aging Clock Via Protein Stability
Using Mass Spectrometry for Protein Complex Analysis
Jul 16, 2018 | Laboratory News, Laboratory Operations, Laboratory Testing, News From Dark Daily
This potential new source of diagnostic biomarkers could give clinical labs a new tool to diagnose disease earlier and with greater accuracy
Clinical laboratories may soon have a new “omics” in their toolkit and vocabulary. In addition to genomics and proteomics, anatomic pathologists could also be using “interactomics” to diagnose disease earlier and with increased accuracy.
At least that’s what researchers at ETH Zurich (ETH), an international university for technology and natural sciences, have concluded. They published the results of their study in Cell.
“Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environments,” the researchers wrote. “Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.”
Interactomics address interactions between proteins and small molecules, according to an article published in Technology Networks. The terms “interactomics” and “omics” were inspired by research that described, for the first time, the interactions and relationships of all proteins and metabolites (A.K.A, small molecules) in the whole proteome.
Medical laboratories and anatomic pathologists have long understood the interactions among proteins, or between proteins and DNA or RNA. However, metabolite interactions with packages of proteins are not as well known.
These new omics could eventually be an important source of diagnostic biomarkers. They may, one day, contribute to lower cost clinical laboratory testing for some diseases, as well.
Metabolite-Protein Interactions are Key to Cellular Processes
The ETH researchers were motivated to explore the interplay between small molecules and proteins because they have important responsibilities in the body. These cellular processes include:
“Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in cells. But our knowledge of the metabolite-protein interaction lags behind our understanding of protein-protein or protein-DNA interactomes,” the researchers wrote in Cell.
Leveraging Limited Proteolysis and Mass Spectrometry
The researchers used limited proteolysis (LiP) technology with mass spectrometry to discover metabolite-protein interactions. Results aside, experts pointed out that the LiP technology itself is significant.
“It is one of the few methods that enables the unbiased and proteome-wide profiling of protein conformational changes resulting from interaction of proteins with compounds,” stated a Biognosys blog post.
Biognosys, a proteomics company founded in 2008, was originally part of a lab at ETH Zurich.
The ETH team focused on the E. coli bacterial cell in particular and how its proteins and enzymes interact with metabolites.
“Although the metabolism of E. coli and associated molecules is already very well known, we succeeded in discovering many new interactions and the corresponding binding sites,” Paola Picotti, PhD, Professor of Molecular Systems Biology at ETH Zurich, who led the research, told Technology Networks. “The data that we produce with this technique will help to identify new regulatory mechanisms, unknown enzymes and new metabolic reactions in the cell,” she concluded. (Photo copyright: ETH Zurich.)
More than 1,000 New Interactions Discovered
The study progressed as follows, according to Technology Networks’ report:
- “Cellular fluid, containing proteins, was extracted from bacterial cells;
- “A metabolite was added to each sample;
- “The metabolite interacted with proteins;
- “Proteins were cut into smaller pieces by molecular scissors (A.K.A., CRISPR-Cas9);
- “Protein structure was altered when it interacted with a metabolite;
- “A different set of peptides emerged when the “molecular scissors” cut at different sites;
- “Pieces of samples were measured with a mass spectrometer;
- “Data were obtained, fed into a computer, and structural differences and changes were reconstructed;
- “1,650 different protein-metabolite interactions were found;
- “1,400 of those discovered were new.”
A Vast, Uncharted Metabolite-protein Interaction Network
The research is a major step forward in the body of knowledge about interactions between metabolites and proteins and how they affect cellular processes, according to Balázs Papp, PhD, Principal Investigator, Biological Research Center of the Hungarian Academy of Sciences.
“Strikingly, more than 80% of the reported interactions were novel and about one quarter of the measured proteome interacted with at least one of the 20 tested metabolites. This indicates that the metabolite-protein interaction network is vast and largely uncharted,” Papp stated in an ETH Zurich Faculty of 1000 online article.
According to Technology Networks, “Picotti has already patented the method. The ETH spin-off Biognosys is the exclusive license holder and is now using the method to test various drugs on behalf of pharmaceutical companies.”
The pharmaceutical industry is reportedly interested in the approach as a way to ascertain drug interactions with cellular proteins and their effectiveness in patient care.
The ETH Zurich study is compelling, especially as personalized medicine takes hold and more medical laboratories and anatomic pathology groups add molecular diagnostics to their capabilities.
—Donna Marie Pocius
Related Information:
The New “Omics”—Measuring Molecular Interactions
Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication
A New Study Maps Protein-Metabolite Interactions in an Unbiased Way
Cell Paper on Protein Metabolite Interactions Recommended in Faculty 1000 Twice
Jan 31, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Researchers are finding multiple approaches to metabolomic research and development involving disparate technology platforms and instrumentation
Human metabolome has been discovered to be a wealth of medical laboratory biomarkers for diagnosis, therapy, and patient monitoring. Because it can provide a dynamic phenotype of the human body, there are many potential clinical laboratory applications that could arise from metabolomics, the study of metabolites.
Researchers are discovering numerous ways the expanding field of metabolomics could transform the future of healthcare. However, to fully exploit the potential of human metabolome, developers must choose from various approaches to research.
“The metabolites we’re dealing with have vast differences in chemical properties, which means you need multi-platform approaches and various types of instrumentation,” James MacRae, PhD, Head of Metabolomics at the Francis Crick Institute in London, told Technology Networks. “We can either use an untargeted approach—trying to measure as much as possible, generating a metabolic profile—or else a more targeted approach where we are focusing on specific metabolites or pathways,” he added.
A multi-platform approach means different diagnostic technologies required to assess an individual’s various metabolomes, which, potentially, could result in multi-biomarker assays for medical laboratories.
Measuring All Metabolites in a Cell or Bio System
Metabolomics is the study of small molecules located within cells, biofluids, tissues, and organisms. These molecules are known as metabolites, and their functions within a biological system are cumulatively known as the metabolome.
Metabolomics, the study of metabolome, can render a real-time representation of the complete physiology of an organism by examining differences between biological samples based on their metabolite characteristics.
“Metabolomics is the attempt to measure all of the metabolites in a cell or bio system,” explained MacRae in the Technology Networks article. “You have tens of thousands of genes, of which tens of thousands will be expressed—and you also have the proteins expressed from them, which will then also be modified in different ways. And all of these things impact on a relatively small number of metabolites—in the thousands rather than the tens of thousands. Because of that, it’s a very sensitive output for the health or physiology of your sample.
“With that in mind, metabolomics has great potential for application in most, if not all, diseases—from diabetes, heart disease, cancer, HIV, autoimmune disease, parasitology, and host-pathogen interactions,” he added.
The graphic above is taken from a study published in the Journal of the American College of Cardiology (JACC). It notes, “State-of-the-art metabolomic technologies give us the ability to measure thousands of metabolites in biological fluids or biopsies, providing us with a metabolic fingerprint of individual patients. These metabolic profiles may serve as diagnostic and/or prognostic tools that have the potential to significantly alter the management of [chronic disease].” (Image and caption copyright:Journal of the American College of Cardiology.)
• Genomics: the study of DNA and genetic information within a cell;
• Proteomics: the large-scale study of proteins; and,
• Transcriptomics: the study of RNA and differences in mRNA expressions.
Researchers caution that metabolomics should be used in conjunction with other methods to analyze data for the most accurate results.
“Taking everything together—metabolic profiling, targeted assays, label incorporation and computational models, and also trying to associate all of this with proteomics and
genomics and transcriptomic data—that’s really what encapsulates both the power and also the challenges of metabolomics,” MacRae explained.
Metabolome in Precision Medicine
Metabolomics may also have the ability to help researchers and physicians fine-tune therapies to meet the specific needs of individual patients.
“We know we’re all very different and we don’t respond to drugs in the same way, so we could potentially use metabolomics to help select the best treatment for each individual,” Warwick Dunn, PhD, Senior Lecturer in Metabolomics at the University of Birmingham, Director of Mass Spectrometry, Phenome Center Birmingham, and, Co-Director, Birmingham Metabolomics Training Center, UK, told Technology Networks.
“Our genome is generally static and says what might happen in the future. And the metabolome at the other end is the opposite—very dynamic, saying what just happened or could be about the happen,” Dunn explained. “So, we could apply it to identify prognostic biomarkers, for example, to predict if someone is at greater risk of developing diabetes five to ten years from now. And if you know that, you can change their lifestyle or environment to try and prevent it.”
Metabolomics continues to tap the many diagnostic possibilities posed by the human metabolome. And, the resulting human biomarkers derived from the research could result in a rich new vein of medical laboratory assays.
—JP Schlingman
Related Information:
Metabolomics and Health: On the Cusp of a Revolution
‘Metabolomics’ Distinguishes Pancreatic Cancer from Pancreatitis
Using Metabolomics to Prevent Colon Cancer
Applications of Metabolomics
The Emerging Role of Metabolomics in the Diagnosis and Prognosis of Cardiovascular Disease
Metabolomics Takes Another Step Forward as Methodology for Clinical Laboratory Testing with Development of an Assay for the Diagnosis of Concussion
Jan 12, 2018 | Laboratory Pathology
Clinical labs and pathology groups know how advances in targeted therapies and genomics far outpace providers’ and patients’ ability to know how best to use and pay for them.
One fascinating development on the road to precision medicine is that many new cancer drugs now in clinical trials will require a companion genetic test to identify patients with tumors that will respond to a specific therapeutic drug.
This implies more genetic testing of tumors, a prospect that challenges both the Medicare program and private health insurers because they already struggle to cope with the flood of new genetic tests and molecular diagnostic assays. However, even as this genetic testing wave swamps payers, some pharmaceutical companies have cancer drugs for rare types of cancers and these companies would like to see more genetic testing of tumors.
Pathologists and clinical laboratory managers will find this to be precisely the dilemma facing specialty pharma company Loxo Oncology (NASDAQ:LOXO), a biopharmaceutical company located in San Francisco and Stamford, Conn.
Loxo is developing larotrectinib (LOXO-101), a “selective TRK inhibitor.” According to a Loxo press release, Larotrectinib is “a potent, oral, and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRK receptors).” In short, the drug is designed to “directly target TRK, and nothing else, turning off the signaling pathway that allows TRK fusion cancers to grow.”
How to Find Patients for This Cancer Drug
While a powerful, new, targeted cancer drug will be a boon to cancer therapy, it is only intended for a relatively small number of patients. Loxo estimates that between 1,500 and 5,000 cases of cancer are caused by TRK mutations in the United States each year. Conversely, according to the National Cancer Institute, the total number of new cancer diagnoses in the US in 2016 was 1,685,210.
An article in MIT Technology Review on larotrectinib notes, “To find patients, Loxo will need to convince more doctors to order comprehensive tests that screen multiple genes at once, including TRK.” And that is where things get complicated.
“These advanced genetic tests, which can cost $5,000 or more, are offered by companies like Foundation Medicine, Caris Life Sciences, and Cancer Genetics. The problem is, insurers still consider the tests ‘experimental’ and don’t routinely cover them, meaning patients are often stuck picking up the bill,” notes MIT Technology Review.
Data for the graph above comes from the National Human Genome Research Institute. The graph illustrates the steep decline in cost for whole genome sequencing over the past 17 years. As the cost of genetic testing drops, development of targeted-drug cancer therapies increases. Clinical laboratories and anatomic pathology groups can expect to be performing more such tests in the future. (Graphic copyright: National Human Genome Research Institute/Simple English Wiki.)
To further confuse the market, the National Cancer Institute states that “Insurance coverage of tumor DNA sequencing depends on your insurance provider and the type of cancer you have. Insurance providers typically cover a DNA sequencing test if there is sufficient evidence to support that the test is necessary to guide patient treatment. Tests without sufficient evidence to support their utility may be considered experimental and are likely not covered by insurance.”
Many reliable sources agree. For example, the US National Library of Medicine Genetics Home Reference states, “In many cases, health insurance plans will cover the costs of genetic testing when it is recommended by a person’s doctor.”
That, however, leads to a different conundrum for drug makers such as Loxo: the majority of doctors are not keeping up with the rapid-fire pace of discovery in the realm of genetics and targeted therapies. Some genes like BRCA1 and BRCA2 are familiar enough to doctors that they know how and why they are important. However, most other genes are less known, and critically, less understood by doctors who must also focus on all the other myriad aspects of patient care.
In an article on the Color Genomics $249 Hereditary Cancer Test, which tests for mutations in 30 genes, Timothy Hamill, MD, Professor Emeritus, University of California San Francisco (UCSF) Department of Laboratory Medicine, and former overall director of UCSF’s clinical laboratories, told Wired, “If you talk to docs, they say ‘BRCA, that’s the only thing I’m interested in because I don’t know what to do with the other information.’ Doctors don’t know what to do with it. Patients don’t know what to do with it.”
More Testing Equals More Knowledge
Further complicating the issue, there is an enormous lack of information on how multipanel screenings will affect individuals, public health, and the cost of healthcare in general. Several studies are underway, but they are so new it could be years before any real results become available.
Five years ago, it cost about $20,000 to sequence the whole human genome. Now the average price is $1,500, though there are more and less expensive types of genetic tests. As the cost continues to decline, however, more people will undergo the testing and scientists will learn more about how to identify the best therapy to treat cancers caused by genetic mutations.
—Dava Stewart
Related Information:
Loxo Oncology Announces Positive Top-Line Results from Independent Review Committee Assessment of Larotrectinib Dataset
National Cancer Institute Statistics
Promising New Cancer Drugs Won’t Go Far Unless Everyone Gets Genetic Testing
Tumor DNA Sequencing in Cancer Treatment
Will Health Insurance Cover the Costs of Genetic Testing?
A Single $249 Test Analyzes 30 Cancer Genes. But Do You Need It?
Personal Genome Test Will Sell at New Low Price of $250
