As genomic sequencing technology advances and its cost continues to fall, the public’s access to genetic information is on the upswing. How this trend will impact clinical laboratories and companies that offer genetic data to consumers remains to be seen.
In 20 years, most people will have the option of having their genomes sequenced, according to James Lu, MD, PhD, co-founder and senior vice president of applied genomics at Helix, a consumer company in San Carlos, California, that sequences DNA. “Data acquisition is going to become easier,” he explained. “Genomic information will become ubiquitous.”
Some scientists expect that more consumer genomic data will make its way to practicing physicians, although certain obstacles exist. Consumer companies also tend to set a good example of how to educate patients about their genetic information.
With that said, clinical laboratories will remain critical to doctors and scientists who need to test for rare diseases and the genetic makeup of cancers to better target treatments, said Honey Reddi, PhD, FACMG, clinical laboratory director of the CLIA lab at The Jackson Laboratory (JAX) in Farmington, Connecticut.
The Tug Between Targeted Panels and Whole Genome Sequencing
In the clinic, genomic data will keep its star role in testing for rare, severe, or undiagnosed diseases, said Euan Ashley, MD, PhD, associate professor of medicine and genetics, co-director of the clinical genomics service, director of the Center for Inherited Cardiovascular Disease, and co-medical director of the Clinical Genomics Program at Stanford University in Stanford, California.
Expert consensus, the history of how syndromes present and overlap, and the “art of medicine” all provide an important context for these data, said Ashley. The future will likely see widespread sequencing using longer read technologies. Short-read sequencing can miss important structural variations in the genome. Whether scientists use short-read or long-read sequencing, depth of coverage is important. However, long-read, deep coverage is expensive, he noted.
Currently, with genomic or exomic sequencing, the signal spread occurs across a large portion of the genome, explained Heidi Rehm, PhD, FACMG, director of the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine and associate professor of pathology at Harvard Medical School in Boston. This means the coverage or depth of signal is lower everywhere compared to a focused analysis.
In contrast, laboratories typically test fewer than 100 genes in a genetic panel, instead of 20,000 as part of whole genome sequencing. Consequently, the depth of coverage is much higher with panels, and laboratories have a better chance of detecting mutations. This suggests that, “for most somatic cancers testing will be panel-based, with just the subset of genes that are known to be clinically relevant,” said Rehm.
The question remains as to whether physicians and laboratories “are going to expand screenings to find a larger number of mutations to provide multiple therapeutic options, rather than just monotherapies for cancer,” said Reddi.
For constitutional testing, “I think we’re already at the exome level,” noted Reddi, adding that exome sequencing is available for newborn congenital abnormalities, autism spectrum disorder, and epilepsy. Taking this to the next step would involve testing the whole genome to evaluate disease-associated regions, she said.
Currently, genomic and exomic sequencing tests are ordered much less frequently than panel tests largely because of lack of insurance coverage, according to Rehm.
From Recreational to Relevant Testing
Because of Food and Drug Administration regulations, recreational genotyping companies are unable to offer much clinically relevant data to users, said Rehm. Most of the markers for complex risk assessments at consumer companies such as 23andMe are not used in the clinic.
However, the carrier status reports 23andMe offers may be useful for family planning purposes, said Rehm. In addition, having information on genetic predisposition for weight gain or other negative factors theoretically might encourage individuals to make healthy lifestyle changes to offset risk, but true beneficial outcomes are unclear, she cautioned.
Yet providing risk assessment information within a regulated environment is critical to patients, said Reddi. If companies want to provide this type of data, they also need to offer genetic counseling services or ensure that health data are incorporated into patients’ medical records. “If a patient comes into the clinic and says, ‘I got this information from 23andMe,’ it’s very rare that doctors are going to act on it because they didn’t order the test,” she said.
While consumer companies typically use genotyping to acquire genetic information, they eventually might try to collect more data through genomic sequencing, said Reddi. However, they need to ensure they have partnerships with CLIA-certified or College of American Pathologists (CAP)-accredited labs and coordinate with insurance companies for reimbursement if testing is to have clinical implications.
Helix offers a custom test, Exome+, which combines a medical exome with a microarray in a single assay performed in a CLIA-certified, CAP-accredited lab. “This provides a comprehensive data set for a single individual,” said Lu. “We’re the first personal genome platform.” Helix stores genomic data on the consumer’s behalf. Customers subsequently access their information through applications that interpret their data. The goal is for clients to be sequenced once and then to use their genomic information as they see fit.
In addition to partnerships with companies such as National Geographic, which has an app called Geno 2.0 that provides clients with ancestral information, Helix has
relationships with more clinically
oriented companies. For example, Sema4, a health information company, uses Helix genomic data to offer consumers CarrierCheck, a screen for carrier status of 67 inherited conditions. Such health apps are for asymptomatic patients who are interested in prevention, noted Lu.
“Fundamentally, it’s a good model to sequence once and interpret often, although the quality of sequencing is still evolving and we may not be ready for this model quite yet,” observed Rehm about Helix. Encouraging a diversity of technical approaches while sequencing methods are still evolving is important, she added. As technologies emerge, Helix likely will migrate to whole genome sequencing, said Lu.
Connecting Consumer Testing to Physicians and Health Systems
Currently, if testing is ordered outside of a physician’s office, any useful results individuals might receive aren’t likely to be entered into an electronic medical record (EMR), noted Rehm. However, Lu suggested that patients should share results from consumer genomics companies with physicians so they can discuss early intervention and screening intervals. Helix applications do not currently integrate health data directly into EMRs. For now, sharing PDF reports is more likely, he said.
Consumer companies already collect large amounts of genomic data at relatively low cost, said Ashley. “The question is, at what point does a healthcare system decide that it’s worth investing in that technology.”
Ashley sees a future in which healthcare facilities might partner with consumer companies to offer genomic screening as a means of differentiating themselves in the marketplace. Another route would be to perform randomized studies of various genomic scoring tools to determine whether patients experience improved outcomes when data are incorporated in the EMR and health management. “Better outcomes would create pressure on healthcare systems, doctors, and payors to offer these scores,” he contended.
Education Eminence
As genomic testing evolves, Rehm is particularly interested in how to best educate patients about test results. Direct-to-consumer companies tend to be better than some physicians at explaining genetic testing and analysis to patients, she noted. Doctors tend to relay information verbally. Clinical test reports often are difficult to understand, but companies like 23andMe have a software interface that gives people immediate access to their genetic information, explaining it in consumer-friendly terms, she added.
Another educational challenge is that, “a variant’s classification might change and there’s no good mechanism across the board to get this information to the patient,” said Rehm. More savvy individuals are checking how their variants change over time in ClinVar, a publically available resource.
Reddi also acknowledged the importance of both patient and physician education. For example, JAX laboratory provides a Cancer Treatment Profile—a targeted panel of 358 cancer-related genes—to facilitate precision therapy. However, people often assume this is a risk assessment or diagnostic tool, which is not the case, she cautioned. Consequently, education for ordering physicians and patients to better understand the technology of big panels, exomes, and whole genome sequencing is essential, she said. JAX has developed education modules on variant analysis and reporting that walks clinicians through an oncology report.
For its more clinically oriented products, Helix is partnering with Mayo Clinic and Geisinger Health, which are developing applications focusing on genomic education for consumers. A better understanding of genomic data helps ensure patients are partners in their care, said Lu. “Your genome is many products,” he said. “You should be able to ask the questions you care about and get results you understand in a responsible fashion.”
Heather Lindsey is a writer based in Maplewood, New Jersey. +Email: [email protected]