by Madhuri Hegde, PhD, FACMG – SVP and Chief Scientific Officer of Global Lab Services at PerkinElmer, Inc.
It’s hard to imagine today, but it once took 13 years and approximately $1B to sequence the human genome. Today – with the advent of next generation sequencing (NGS) and related technologies – this process takes just a few days, and there have been approximately 6,000 genes shown to be causative of ~7,000 disorders. With increasingly advanced technologies at their disposal, genomics laboratories are helping physicians marry genetic data with other information and resources to provide a more detailed view of an individual’s health profile. In fact, a more apt term to use these days is in place of genomics is multiomics.
In 2022, we will see increased interest and applications of multiomics in health care. This approach will continue to improve our understanding of the human genome, and how individual genes and their variants may make an individual more likely to be diagnosed with certain conditions or diseases. With broad, global applications of multiomics, public health stands to improve greatly—and here’s how.
Technological Underpinnings
There could be no discussion of multiomics without proper discussion of the technologies enabling it. Whole genome sequencing (WGS) is foremost among them, and has demonstrated its ability to improve the accurate diagnosis of rare diseases by up to 55%.1 In fact, the research that yielded this datapoint showed that of all the genetic diagnoses made, 25% of findings immediately impacted healthcare decisions for patients and their relatives.1
Unlike Whole Exome Sequencing (WES)—which analyzes the coding regions of an individual’s DNA—WGS examines both coding and non-coding regions of the genome, making it more likely to identify certain DNA variations that affect gene activity and protein production, which might otherwise go undetected by WES. Several years ago, WGS cost thousands of dollars and took several months to complete. Fortunately, over time there have been significant improvements that reduce cost and turnaround time for results—making it more accessible and useful than ever before.
Sequencing alone, however, is not enabling multiomics. There are plenty more platforms, such as mass spectrometry and other traditional and newer technologies that revolve around it, which are enabling equally important discoveries. Furthermore, tertiary technologies like workflow automation and laboratory management software further optimize efficiency and quality of WGS test results.
Global Approach
Improving access to WGS, and multiomics, must be a priority on a global scale.
Around the world, the approach to genetic testing is often a bit different country to country, due in part to varying health systems, resource availability, workforce training, etc. However, because certain genetic variants exist only within specific populations, it is incredibly important that local laboratories are established to conduct genetic testing within local, cultural context and specific to the individuals in that region. In low and middle-income countries, local genomics labs can be especially impactful, particularly in improving access to genomic testing starting with newborn screening.
According to one estimate, of the roughly 134 million babies born globally each year, just about one-third of these newborns receive screening of any type. That screening varies country by country, and in many cases, is for one or two conditions out of the 70 tests available for screening potentially life-threatening disorders.
A key contributing factor to the underutilization of newborn screening is limited awareness of rare diseases, their prevalence, impact on families and cost to the healthcare system. In some geographies, clinical researchers and physicians lack the necessary information to make timely and accurate diagnoses. Cost and resource constraints present additional challenges for newborn screening programs, which should ideally also include education, counseling and other components above and beyond the tests alone. Furthermore, newborn screening for all babies – even seemingly healthy newborns – is not implemented widely. As a result, rare diseases and disorders that are potentially life-endangering, yet relatively uncomplicated to treat, can go undiagnosed.
Congenital hyperthyroidism (CH) is one of these conditions. In greater than 95% of newborns with CH, there are no signs or symptoms presented at the time of birth, and if left untreated, CH has been known to cause permanent neurodevelopmental deficits.
Healthcare costs for people with a rare disease like CH are three to five times greater than the costs for people without a rare disease, often on par with the medical costs for cancer and heart failure.2 Some of this increased cost can be attributed to long diagnostic journeys exacerbated by slow or inaccurate diagnoses. This is yet another reason to extend the reach of multiomics globally.
Beyond benefiting public health at the local level, genomics labs around the world can make substantial progress improving the diversity in shared genetics databases.
Collaboration and Continued Information Sharing
A fundamental aspect of ensuring multiomics improves health care outcomes globally is continued collaboration in the scientific community. As researchers contribute their findings and unique insights to shared genetic databases such as ClinVar, our understanding of health and disease grows. Collaboration will also fuel progress in the area of variant classification – an incredibly challenging task, even for the most seasoned geneticists.
As shared genetics databases grow over time – and information within them better represents people around the globe – we can ensure good generalizability in research studies and empower health care providers to make more timely diagnoses. Only then can proper medical interventions be prescribed and lead to better health care outcomes.
Putting Multiomics Into Action
In 2021, the American College of Medical Genetics and Genomics (ACMG) established a task force to focus on international outreach and raise awareness of the ACMG and its activities. Intentionally, this task force sought members with diverse perspectives and innovative ideas, in the same spirit of localized genetic research programs. Even still, geneticists alone will not make multiomics more widespread. There is an entire ecosystem of organizations that can help achieve this goal.
Large, global pharmaceutical and biotechnology companies can play an equally impactful role with their vast resources and area expertise in the varying disciplines within multiomics. In some cases, these organizations can offer free or significantly reduced testing to patients and families to more rapidly diagnose rare diseases, including but not limited to lysosomal storage diseases, Duchenne or Becker muscular dystrophy, mucopolysaccharidosis disorders, and chronic anemia. In other cases, they can play a leading role in developing novel treatments. Working in partnership with non-profits, NGOs and other public sector organizations, these various vested parties can and will propel important multiomics based discoveries.
Beyond 2022, we can expect continued innovation in terms of how multiomics is put into action – likely for decades to come.
References
- Smedley D, et al. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report. N Engl J Med 2021; 385:1868-80. doi: 10.1056/NEJMoa2035790
- Tisdale A, Cutillo CM, Nathan R, et al. The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems. Orphanet J Rare Dis. Published online October 21, 2021. doi:10.1186/s13023-021-02061-3
About the Author: Madhuri Hegde, PhD, is a medical geneticist and serves as the Senior Vice President and Chief Scientific Officer of Global Lab Services at PerkinElmer, Inc. Dr. Hedge is a board certified diplomat in clinical molecular genetics by the American Board of Medical Genetics and is an ACMG Fellow. Previously, she was the Executive Director of Emory Genetics Laboratory. She received a B.Sc. and M.Sc. from the University of Bombay and a Ph.D. from the University of Auckland. She completed post-doctoral studies at Baylor College of Medicine.