Ever since the Human Genome Project helped usher in our modern genetic age, advances in understanding how DNA contributes to our biology have barreled ahead. Every week, doctors and researchers are making new discoveries about how our genes, and the proteins they code for, contribute to both health and disease. And this has never been more salient than in the youngest among us. Genomic testing can now give families and doctors invaluable insights into solving diagnostic odysseys, timely intervention, and their children’s future health. Whereas a few decades ago, doctors could only test for a narrow range of specific disorders, now a baby’s entire genome can be sequenced and analyzed in a matter of days. The same can be said for a patient’s exome, or just the stretches of DNA that actually code for proteins and enzymes – the molecules that help make life possible.


PerkinElmer Genomics is at the forefront of developing and distributing whole genome and exome sequencing. Today we’ll be speaking with Dr. Madhuri Hegde, Senior Vice President and Chief Scientific Officer of Global Lab Services at PerkinElmer. Dr. Hegde is responsible for developing the scientific portfolio and the commercial strategy for PerkinElmer’s global laboratories. She’s a member of the PerkinElmer leadership team and played a vital role in leading operations for COVID laboratory testing. Today we’re discussing ultrarapid genomic testing for critically ill infants and the overall genomic landscape and how it has changed in the last few years. 


Q – Your work at PerkinElmer focuses on genomic testing. Tell us about what tests are available and how widely they are available.


A – PerkinElmer Genomics has a global footprint, and our testing reaches 155 countries. We have labs in the US, India, Malaysia, Sweden, and China. This global in-country-for-country footprint is important because our menu of available tests is really tailored to each country itself.


But generally speaking, as far as our newborn testing goes, we do typical DNA-based testing and a broad range of omics-based assays including immunology. For this particular conversation, I will focus on DNA, and our technology’s ability to perform genome sequencing. And I will make a distinction between “genetic” testing – which looks at individual genes – and “genomic” testing, which looks at the biochemical interactions between the whole genome and the proteins it codes for.


Q – Does the acceptance of newborn genetic testing vary significantly between certain countries and cultures?  


A – Absolutely. If you look at India, the approach to ordering testing is very different from what you would do in the US. For example, newborn screening is not a nationally mandated program in India. Another big difference is in knowing the secondary genetic findings, as opposed to testing for one specific condition when a child appears to have symptoms of the disease in question. We have gone a long way in the last few years to tailor our testing accordingly for each country.


Q – How widespread is exome or whole genome sequencing at the moment? And which types of doctors and health systems are ordering these tests?


A – Generally speaking, there is much more education around genetics and genomics these days and physicians are aware that answers are available to them and can be sought out. 


In healthy newborns, sequencing is being done through our ViaCord® blood banking channel, which we launched in 2017. Obviously, we got caught in the middle of the COVID pandemic, but awareness is picking up among physicians and families. 


In ill newborns, the doctors ordering these tests include neonatologists, pediatricians, clinical geneticists, neurologists, kidney specialists, and heart specialists. All are consistently ordering genomic testing now, among other specialists.


Q – How does the relationship between PerkinElmer Genomics and physicians begin?


A – Typically, through a hospital or outpatient clinic. Essentially, hospitals often have an arrangement with PerkinElmer Genomics to send the samples to us. We also give talks and public presentations to improve awareness among doctors. The interaction often starts when they have a baby for whom they need clinical answers in order to decide on the next steps for treatment. 


Genome sequencing is now slowly making its way into typical clinical settings. Instead of going through a cascade of increasingly wide tests, physicians can order whole genome sequencing and get most of the answers they might need in one test. We can turn around these tests in 5 days or in some cases less depending on the urgency.


Q – Walk us through some of the specific conditions your technology is frequently used to test for.


A – Let’s look at newborn screening. Per the recommended universal screening panel, there are 29 disorders you can look at – these are biochemical disorders. So, typically when a baby is born, within about 24 to 48 hours, blood is taken from a heel prick and sent to a screening laboratory, such as ours. If the baby already has a clinical presentation, then ultrarapid whole genome sequencing can be ordered and that will pick up most of the biochemical disorders as well as look at the full genome to help providers and parents make clinical decisions. 


What we have done is we have gone a step ahead.


We have to remember that whole genome sequencing is a piece of the puzzle. It’s one test. What we have done at PerkinElmer Genomics is combined it with comprehensive biochemical testing. So instead of only testing for 29 disorders, we’re testing for ~97 disorders plus looking at the baby’s entire genome. Now, why would we do that? This way we can pick up both altered enzyme levels that code for some genes associated with a disease, as well as genetic mutations in the baby. This is your first level – metabolic conditions. Then you can test for your second level – cardiac conditions, kidney issues, and the whole range of disorders that can be picked up through whole genome sequencing. 


Q – So when you say biochemical testing, you’re talking about proteins or enzymes that are coded for by pathogenic gene variants, right? Whereas whole genome sequencing alone doesn’t provide this information?


A – Yes, having a functional enzyme assay makes the test more powerful. But sometimes we cannot interpret the DNA changes and tell whether they will cause disease or not. Combining whole genome sequencing with biochemical testing provides a more robust solution for providers and parents when diagnosing critically ill newborns.  


Q – When you do receive results indicating that an infant might be at risk for a disease, what are the next steps in terms of counseling and care?


A – Let’s take childhood epilepsy, for instance.Once we have issued a clinical report saying that it’s a pathogenic variant, the next step for the physician is to decide the course of treatment. There are now drugs that can be used to first stop the seizures. Many aren’t curative, but they can stop disease progression or should not be prescribed. This is also the case for many metabolic conditions related to a specific enzyme deficiency. Here enzyme replacement therapies are often available.


Really the whole point of going through rapid genome testing is to find answers as soon as possible so that the physician can intervene in a more effective way.   


Q – You’re working with a very broad array of specialties – neurologists, cardiologists, nephrologists, and genetic counselors among them. How does the clinician relationship with PerkinElmer Genomics function? 


A – Great question. It really depends on who has ordered the test. Whether it’s a neonatologist for example or a geneticist. Either way, first, genetic counseling enters the picture early and is a critical part of clinical reporting.


Second, while we obviously do not guide treatment, we do give the full information of what that condition actually is. Regardless of whether it’s the neonatologist or geneticist ordering the test, we provide a detailed explanation of the gene, the mutation, and the potential consequences.


Then they can take the information to their team of physicians, those actually caring for the baby.   Lastly, they may come back to us and ask more questions about certain mutations, as some are specific to certain populations, and are amenable to treatment. As I mentioned at the beginning of our conversation, PerkinElmer Genomics is in 155 countries, and our laboratories have a global footprint. So, a lot of times, we are in a unique position to provide that information, because we really have made whole genome sequencing our mission.