Solving Common Hematopathology Testing Challenges with Next-Generation Sequencing
Solving Common Hematopathology Testing Challenges with Next-Generation Sequencing FREE Webinar Held Wednesday, August 12 Now a Streaming Webinar Hematological malignancies are complex, heterogeneous disorders involving multiple recurrent somatic and germline mutations. For acute hematological malignancies, early diagnosis and personalized disease management remain serious challenges. Moreover, there is a growing need for reliable and timely detection of minimal residual disease...Advances in Gene Sequencing Technology Enable Scientists to Respond to the Novel Coronavirus Outbreak in Record Time with Medical Lab Tests, Therapies
Scientist described the speed at which SARS-CoV-2’s full sequence of genetic material was made public as ‘unprecedented’ and medical labs are rushing to validate tests for this new disease
In the United States, headlines scream about the lack of testing for the novel Coronavirus disease 2019 (COVID-19). News reporters ask daily why it is taking so long for the US healthcare system to begin testing large numbers of patients for SARS-CoV-2, the virus that causes COVID-19. Yet, pathologists and clinical laboratory scientists know that new technologies for gene sequencing and diagnostic testing are helping public health laboratories bring up tests for a previously unknown new disease faster than at any time in the past.
At the center of the effort to develop accurate new assays to detect SARS-CoV-2 and help diagnose cases of the COVID-19 disease are medical laboratory scientists working in public health laboratories, in academic medical centers, and in research labs across the United States. Their collective efforts are producing results on a faster timeline than in any previous discovery of a new infectious disease.
For example, during the severe acute respiratory syndrome (SARS) outbreak in 2003, five months passed between the first recognized case of the disease in China and when a team of Canadian scientists cracked the genetic code of the virus, which was needed to definitively diagnose SARS patients, ABC News reported.
In contrast, Chinese scientists sequenced this year’s coronavirus (originally named 2019-nCoV) and made it available on Jan. 10, 2020, just weeks after public health officials in Wuhan, China, reported the first case of pneumonia from the unknown virus to the World Health Organization (WHO), STAT reported.
Increases in sequencing speed enabled biotechnology companies to quickly create synthetic copies of the virus needed for research. Roughly two weeks later, scientists completed sequencing nearly two dozen more samples from different patients diagnosed with COVID-19.
Lower Sequencing Costs Speed COVID-19 Diagnostics Research
Additionally, a significant decline in the cost of genetic synthesis is playing an equally important role in helping scientists slow the spread of COVID-19. In its coverage of the SARS-CoV-2 outbreak, The Verge noted that two decades ago “it cost $10 to create a synthetic copy of one single nucleotide, the building block of genetic material. Now, it’s under 10 cents.” Since the coronavirus gene is about 30,000 nucleotides long, that price reduction is significant.
Faster sequencing and cheaper access to synthetic copies is contributing to the development of diagnostic tests for COVID-19, an important step in slowing the disease.
On Feb. 4, 2020, the US Food and Drug Administration (FDA) issued its first emergency use authorization (EUA) for a diagnostic test for the coronavirus called 2019-nCoV Real-Time RT-PCR Diagnostic Panel. The test was developed by the US Centers for Disease Control and Prevention (CDC).
“This continues to be an evolving situation and the ability to distribute this diagnostic test to qualified medical laboratories is a critical step forward in protecting the public health,” FDA Commissioner Stephen M. Hahn, MD, said in an FDA statement.
However, the Washington Post soon reported that the government-created coronavirus test kits contained a “faulty component,” which as of February 25 had limited testing in the US to only 426 people, not including passengers who returned to the US on evacuation flights. The Post noted that the nation’s public health laboratories took “the unusual step of appealing to the FDA for permission to develop and use their own [laboratory-developed] tests” for the coronavirus.
“This is an extraordinary request, but this is an extraordinary time,” Scott Becker,
Chief Executive of the Association of Public Health Laboratories (APHL), told the Post.
Parallel efforts to develop and validate tests for COVID-19 are happening at the clinical laboratories of academic medical centers and in a number of commercial laboratory companies. As these labs show their tests meet FDA criteria, they become available for use by physicians and other healthcare providers.
Dark Daily’s sister publication, The Dark Report just published an intelligence briefing about the urgent effort at the clinical laboratory of Northwell Health to develop both a manual COVID-19 assay and a test that can be run on the automated analyzers already in use in the labs at Northwell Health’s 23 hospitals. (See TDR, “Northwell Lab Team Validates COVID-19 Test on Fast Timeline,” March 9, 2020.)
Following the FDA’s March 13 EUA for the Thermo Fisher test, Hahn said, “We have been engaging with test developers and encouraging them to come to the FDA and work with us. Since the beginning of this outbreak, more than 80 test developers have sought our assistance with development and validation of tests they plan to bring through the Emergency Use Authorization process. Additionally,” he continued, “more than 30 laboratories have notified us they are testing or intend to begin testing soon under our new policy for laboratory-developed tests for this emergency. The number of products in the pipeline reflects the significant role diagnostics play in this outbreak and the large number of organizations we are working with to bring tests to market.”
So far, the FDA has issued a total of seven EUAs:
- CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel (CDC);
- New York SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel (Wadsworth Center, NYSDOH);
- cobas SARS-CoV-2 (Roche);
- TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Inc.);
- Panther Fusion SARS-CoV-2 (Hologic, Inc.);
- COVID-19 RT-PCR Test (Laboratory Corporation of America);
- Lyra SARS-CoV-2 Assay (Quidel Corp.);
- Quest SARS-CoV-2 rRT-PCR (Quest Diagnostics Infectious Disease, Inc.).
Pharma Company Uses Sequencing Data to Develop Vaccine in Record Time
Even as clinical laboratories work to develop and validate diagnostic tests for COVID-19, drug manufacturers are moving rapidly to develop a COVID-19 vaccine. In February, Massachusetts-based biotechnology company Moderna Therapeutics (NASDAQ:MRNA) announced it had shipped the first vials of its potential coronavirus vaccine (mRNA-1273) to the National Institute of Allergy and Infectious Disease (NIAID) for use in a Phase One clinical trial.
“The collaboration across Moderna, with NIAID, and with CEPI [Coalition for Epidemic Preparedness Innovations] has allowed us to deliver a clinical batch in 42 days from sequence identification,” Juan Andres, Chief Technical Operations and Quality Officer at Moderna, stated in a news release.
The Wall Street Journal (WSJ) reported that NIAID expects to start a clinical trial of about 20 to 25 healthy volunteers by the end of April, with results available as early as July or August.
“Going into a Phase One trial within three months of getting the sequence is unquestionably the world indoor record,” NIAID Director Anthony Fauci, MD, told the WSJ. “Nothing has ever gone that fast.”
There are no guarantees that Moderna’s coronavirus vaccine will work. Furthermore, it will require further studies and regulatory clearances that could delay widespread distribution until next year.
Nonetheless, Fauci told the WSJ, “The only way you can completely suppress an emerging infectious disease is with a vaccine. If you want to really get it quickly, you’re using technologies that are not as time-honored as the standard, what I call antiquated, way of doing it.”
In many ways, the news media has overlooked all the important differences in how fast useful diagnostic and therapeutic solutions for COVID-19 are moving from research settings into clinical use, when compared to early episodes of the emergence of a new infectious disease, such as SARS in 2003.
The story the American public has yet to learn is how new genetic sequencing technologies, improved diagnostic methods, and enhanced informatics capabilities are being used by researchers, pathologists, and clinical laboratory professionals to understand this new disease and give healthcare professionals the tools they need to diagnose, treat, and monitor patients with COVID-19.
—Andrea Downing Peck
Related Information:
To Fight the Coronavirus, Labs Are Printing Its Genome
DNA Sleuths Read the Coronavirus Genome, Tracing Its Origins and Looking for Dangerous Mutations
Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization to Thermo Fisher
A Faulty CDC Coronavirus Test Delays Monitoring of Disease’s Spread
Moderna Ships mRNA Vaccine Against Novel Coronavirus (mRNA-1273) for Phase 1 Study
Drugmaker Moderna Delivers First Experimental Coronavirus Vaccine for Human Testing
China Detects Large Quantity of Novel Coronavirus at Wuhan Seafood Market
Scientists Claim SARS Breakthrough
Discovery of ‘Hidden’ Outbreak Hints That Zika Virus Can Spread Silently
Research Use Only Real-Time RT-PCR Protocol for Identification of 2019-nCoV
Emergency Use Authorization (EUA) Information and List of All Current EUAs
AdventHealth Gives 10,000 Floridians Free Genetic Tests, Sees Genomics as the Future of Precision Medicine
Many other healthcare systems also are partnering with private genetic testing companies to pursue research that drive precision medicine goals
It is certainly unusual when a major health network announces that it will give away free genetic tests to 10,000 of its patients as a way to lay the foundation to expand clinical services involving precision medicine. However, pathologists and clinical laboratory managers should consider this free genetic testing program to be the latest marketplace sign that acceptance of genetic medicine continues to move ahead.
Notably, it is community hospitals that are launching this new program linked to clinical laboratory research that uses genetic tests for specific, treatable conditions. The purpose of such genetic research is to identify patients who would benefit from test results that identify the best therapies for their specific conditions, a core goal of precision medicine.
The health system is AdventHealth of Orlando, Fla., which teamed up with Helix, a personal genomics company in San Mateo, Calif., to offer free DNA sequencing to 10,000 Floridians through its new AdventHealth Genomics and Personalized Health Program. A company news release states this is the “first large-scale DNA study in Florida,” and that it “aims to unlock the secret to a healthier life.”
The “WholeMe” genomic population health study screens people for familial hypercholesterolemia (FH), a genetic disorder that can lead to high cholesterol and heart attacks in young adults if not identified and treated, according to the news release.
Clinical laboratory leaders will be interested in this initiative, as well other partnerships between healthcare systems and private genetic testing companies aimed at identifying and enrolling patients in research studies for disease treatment protocols and therapies.
The Future of Precision Medicine
Modern Healthcare reported that data from the WholeMe DNA study, which was funded through donations to the AdventHealth Foundation, also will be used by the healthcare network for research beyond FH, as AdventHealth develops its genomics services. The project’s cost is estimated to reach $2 million.
“Genomics is the future of medicine, and the field is rapidly evolving. As we began our internal discussions about genomics and how to best incorporate it at AdventHealth, we knew research would play a strong role,” Wes Walker MD, Director, Genomics and Personalized Health, and Associate CMIO at AdventHealth, told Becker’s Hospital Review.
“We decided to focus on familial hypercholesterolemia screening initially because it’s a condition that is associated with life-threatening cardiovascular events,” he continued. “FH is treatable once identified and finding those who have the condition can lead to identifying other family members who are subsequently identified who never knew they had the disease.”
The AdventHealth Orlando website states that participants in the WholeMe study receive information stored in a confidential data repository that meets HIPAA security standards. The data covers ancestry and 22 other genetic traits, such as:
- Asparagus Odor Detection
- Bitter Taste
- Caffeine Metabolism
- Cilantro Taste Aversion
- Circadian Rhythm
- Coffee Consumption
- Delayed Sleep
- Earwax Type
- Endurance vs Power
- Exercise Impact on Weight
- Eye Color
- Freckling
- Hair Curl and Texture
- Hand Grip Strength
- Height
- Lactose Tolerance
- Sleep Duration
- Sleep Movement
- Sleeplessness
- Sweet Tooth
- Tan vs. Sunburn
- Waist Size
Those who test positive for a disease-causing FH variant will be referred by AdventHealth for medical laboratory blood testing, genetic counseling, and a cardiologist visit, reported the Ormond Beach Observer.
One in 250 people have FH, and 90% of them are undiagnosed, according to the FH Foundation, which also noted that children have a 50% chance of inheriting FH from parents with the condition.
AdventHealth plans to expand the free testing beyond central Florida to its 46 other hospitals located in nine states, Modern Healthcare noted.
Other Genetics Data Company/Healthcare Provider Partnerships
In Nevada, Helix partnered with the Renown Health Institute for Health Innovation (IHI) and the Desert Research Institute (DRI) to sequence 30,000 people for FH as part of the state’s Healthy Nevada Project (HNP).
Business Insider noted that Helix has focused on clinical partnerships for about a year and seems to be filling a niche in the genetic testing market.
“Helix is able to sidestep the costs of direct-to-consumer marketing and clinical test development, while still expanding its customer base through predefined hospital networks. And the company is in a prime position to capitalize on providers’ interest in population health management,” Business Insider reported.
Another genomics company, Color of Burlingame, Calif., also has population genomics programs with healthcare networks, including NorthShore University Health System in Ill.; Ochsner Health System in La.; and Jefferson Health in Philadelphia.
Ochsner’s program is the first “fully digital population health program” aimed at including clinical genomics data in primary care in an effort to affect patients’ health, FierceHealthcare reported.
In a statement, Ochsner noted that its innovationOchsner (iO) program screens selected patients for:
- Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2 genes;
- Lynch syndrome, associated with colorectal and other cancers; and
- FH.
Color also offers genetic testing and whole genome sequencing services to NorthShore’s DNA10K program, which plans to test 10,000 patients for risk for hereditary cancers and heart diseases, according to news release.
And, Jefferson Health offered Color’s genetic testing to the healthcare system’s 33,000 employees, 10,000 of which signed up to learn their health risks as well as ancestry, a Color blog post states.
Conversely, Dark Daily recently reported on two Boston healthcare systems that started their own preventative gene sequencing clinics. The programs are operated by Brigham and Women’s Hospital and Massachusetts General Hospital (MGH).
And a Precision Medicine Institute e-briefing reported on Geisinger Health and Sanford Health’s move to offer genetic tests and precision medicine services in primary care clinics.
“Understanding the genome warning signals of every patient will be an essential part of wellness planning and health management,” said Geisinger Chief Executive Officer David Feinberg, MD, when he announced the new initiative at the HLTH (Health) Conference in Las Vegas. “Geisinger patients will be able to work with their family physician to modify their lifestyle and minimize risks that may be revealed,” he explained. “This forecasting will allow us to provide truly anticipatory healthcare instead of the responsive sick care that has long been the industry default across the nation.”
It will be interesting to see how and if genetic tests—free or otherwise—will advance precision medicine goals and population health treatments. It’s important for medical laboratory leaders to be involved in health network agreements with genetic testing companies. And clinical laboratories should be informed whenever private companies share their test results data with patients and primary care providers.
—Donna Marie Pocius
Related Information:
AdventHealth Offers Free DNA Tests to 10,000 Floridians
How AdventHealth Orlando is Building a Future in Genomics
Helix Partners with AdventHealth to Offer 10,000 Genetic Screenings in Florida
AdventHealth to Launch Large Genetic Study for High Cholesterol
Ochsner Health System Teaming Up with Genetic Testing Company Color in Population Genomics
The Healthy Nevada Project: from Recruitment to Real-World Impact
Ochsner Health System to Pilot Genetic Screening Program in Partnership with Color
North Shore and Color Unlock the Power of Genomics in Routine Care
Jefferson Heath and Color Advancing Precision Health Through Clinical Genomics and Richer Data
Veritas Genetics Drops Its Price for Clinical-Grade Whole-Genome Sequencing to $599, as Gene Sequencing Costs Continue to Fall
Low prices to encourage consumers to order its WGS service is one way Veritas co-founder and genetics pioneer George Church hopes to sequence 150,000 genomes by 2021
By announcing an annotated whole-genome sequencing (WGS) service to consumers for just $599, Veritas Genetics is establishing a new price benchmark for medical laboratories and gene testing companies. Prior to this announcement in July, Veritas priced its standard myGenome service at $999.
“There is no more comprehensive genetic test than your whole genome,” Rodrigo Martinez, Veritas’ Chief Marketing and Design Officer, told CNBC. “So, this is a clear signal that the whole genome is basically going to replace all other genetic tests. And this [price drop] gets it closer and closer and closer.”
Pathologists and clinical laboratory managers will want to watch to see if Veritas’ low-priced, $599 whole-genome sequencing becomes a pricing standard for the genetic testing industry. Meanwhile, the new price includes not only the sequencing, but also an expert analysis of test results that includes information on more than 200 conditions, Veritas says.
“The focus in our industry is shifting from the cost of sequencing genomes to interpretation capabilities and that’s where our secret sauce is,” said Veritas CEO Mirza Cifric in a news release. “We’ve built and deployed a world class platform to deliver clinically-actionable insights at scale.” The company also says it “achieved this milestone primarily by deploying internally-developed machine learning and AI [artificial intelligence] tools as well as external tools—including Google’s DeepVariant—and by improving its in-house lab operations.”
The myGenome service offers 30x WGS, which Veritas touts in company documentation as the “gold standard” for sequencing, compared to the less-precise 0.4x WGS.
The myGenome service is available only in the United States.
Will Whole-Genome Sequencing Replace Other Genetic Tests?
Veritas was co-founded by George Church, PhD, a pioneer of personal genomics through his involvement with the Harvard Personal Genome Project at Harvard Medical School. In a press release announcing the launch of myGenome in 2016, Veritas described its system as “the world’s first whole genome for less than $1,000, including interpretation and genetic counseling.”
Church predicts that WGS will someday replace other genetic tests, such as the genotyping used by personal genomics and biotechnology company 23andMe.
“Companies like 23andMe that are based on genotyping technology basically opened the market over the last decade,” Martinez explained in an interview with WTF Health. “They’ve done an incredible job of getting awareness in the general population.”
However, he goes on to say, “In genotyping technology, you are looking at very specific points of the genome, less than half of one percent, a very small amount.”
Martinez says Veritas is sequencing all 6.4 billion letters of the genome. And, with the new price point, “we’re closer to realizing that seismic shift,” he said in the news release.
“This is the inflection point,” Martinez told CNBC. “This is the point where the curve turns upward. You reach a critical mass when you are able to provide a product that gives value at a specific price point. This is the beginning of that. That’s why it’s seismic.”
Payment Models Not Yet Established by Government, Private Payers
However, tying WGS into personalized medicine that leads to actionable diagnoses may not be easy. Robin Bennett, PhD (hon.), a board certified senior genetic counselor and Professor of Medicine and Medical Genetics at UW School of Medicine, told CNBC, “[Healthcare] may be moving in that direction, but the payment for testing and for services, it hasn’t moved in the preventive direction. So, unless the healthcare system changes, these tests may not be as useful because … the healthcare system hasn’t caught up to say, ‘Yes, we support payment for this.’”
Kathryn Phillips, PhD, Professor of Health Economics at University of California, San Francisco, says insurers are uncertain that genetic sequencing will lead to clinical diagnoses.
“Insurers are looking for things where, if you get the information, there’s something you can do with it and that both the provider and the patient are willing and able to use that information to do things that improve their health,” Phillips told CNBC. “Insurers are very interested in using genetic testing for prevention, but we need to . . . demonstrate that the information will be used and that it’s a good trade-off between the benefits and the costs.”
Sequencing for Free If You Share Your Data
Church may have an answer for that as well—get biopharmaceutical companies to foot the bill. Though Veritas’ new price for their myGenome service is significantly lower than before, it’s not free. That’s what Nebula Genomics, a start-up genetics company in Massachusetts co-founded by Church, offers people willing to share the data derived from their sequencing. To help biomedical researchers gather data for their studies, Nebula provides free or partially-paid-for whole-genome sequencing to qualified candidates.
“Nebula will enable individuals to get sequenced at much lower cost through sequencing subsidies paid by the biopharma industry,” Church told BioSpace. “We need to bring the costs of personal genome sequencing close to zero to achieve mass adoption.”
Dark Daily reported on Nebula’s program in “Nebula Genomics Offers FREE Whole Genome Sequencing to Customers Willing to Allow Their Data Be Used by Researchers for Drug Development,” January 7, 2019.
So, will lower-priced whole-genome sequencing catch on? Perhaps. It’s certainly popular with everyday people who want to learn their ancestry or predisposition to certain diseases. How it will ultimately affect clinical laboratories and pathologists remains to be seen, but one thing is certain—WGS is here to stay.
—Stephen Beale
Related Information:
23andMe Competitor Veritas Genetics Slashes Price of Whole Genome Sequencing 40% to $600
Veritas Genetics Launches $999 Whole Genome and Sets New Standard for Genetic Testing
