Children’s Mercy Kansas City is one of four sites participating in Newborn Sequencing In Genomic Medicine and Public HealTh (NSIGHT), which is sponsored by the NIH along with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI).
NSIGHT is designed to explore the implications, challenges and opportunities associated with the possible use of genomic sequence information in the newborn period.
The emphasis of the Children’s Mercy NSIGHT project is gaining rapid access to genetic diagnostic information so that clinical care can be managed effectively for acutely ill neonates.
Early evidence of the feasibility of this approach was recently published by Children’s Mercy investigators in The Lancet Respiratory Medicine.
Conclusions from this study suggest that STAT-Seq, a rapid whole-genome sequencing test developed at Children’s Mercy, has the potential to alter clinical management or genetic counseling and provides a novel framework for implementing precision medicine in a level 4 NICU or PICU.
Josh Petrikin, MD is here to discuss Genomics of Newborns.
Selected Podcast
Genomics of Newborns: The Value of Rapid Genetic Testing in the NICU
Featured Speaker:
Josh Petrikin, MD
Joshua E. Petrikin, MD, a Neonatologist at Children’s Mercy Kansas City, since 2009, received his MD from the University of Oklahoma College of Medicine. He also serves as Director, Neonatal Genomics at the Center for Pediatric Genomic Medicine at Children’s Mercy, and is an Assistant Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine. He performed his post-graduate education and training at the Mayo Graduate School of Medicine in Rochester, Minnesota, and completed his fellowship in Neonatology at Children’s Mercy Kansas City. Dr. Petrikin’s clinical practice and research interests are neonatology, bioethics, child advocacy and infant immunology. His primary research focuses on genome sequencing and ethical issues in neonatal genomics. Transcription:
Genomics of Newborns: The Value of Rapid Genetic Testing in the NICU
Dr. Michael Smith (Host): Welcome to Transformational Pediatrics. I am Dr. Mike Smith, and our topic is Genomics of Newborns: the Value of Rapid Genetic Testing in the NICU. My guest is Dr. Josh Petrikin. He’s the director of Saint Joseph’s Help Center Nursery and serves as director of Neonatal Genomics at the Center for Pediatric Genomic Medicine at Children’s Mercy. He’s also the assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine. Dr. Petrikin, welcome to the show.
Dr. Josh Petrikin (Guest): Thank you. It’s a pleasure to be here.
Dr. Smith: Based on your bio, you’re a very busy man, aren’t you, Josh?
Dr. Petrikin: Well, it feels like it, yes.
Dr. Smith: Let’s start with a real simple question. What exactly is rapid genetic testing?
Dr. Petrikin: Sure. Well, standard genetic testing is the sort of thing that is still common today but that we’ve come to expect from the last 10 years or so is usually sequencing of one particular gene using standard Sanger sequencing. Not be too technical about it, but sanger sequencing is how we originally sequence the human genome, and that was a project that took more than a decade and billions of dollars. It’s very accurate but relatively slow. And as anybody that’s sent away gene panels or particular genetic testing is that you get results in weeks to months, sometimes six months or more. So, rapid genetic testing is really anything faster than that. And more specifically, what we’re able to do and are investigating here in Children’s Mercy Kansas City is rapid whole-genome sequencing, where we have the ability to sequence the entire genome of a patient, do the actual sequencing and interpretation in as short as 50 hours, and we’re actually pushing that to see if we can get it to about 24 hours.
Dr. Smith: That’s pretty impressive, right? That’s pretty amazing considering that at one point, as you mentioned, it could take weeks to get a result. Who actually should get this done? What kind of patient are we talking about here? And what’s the end goal here? What’s the value of it, really?
Dr. Petrikin: Sure. That’s an excellent question. It’s an excellent question because we don’t really know the answer yet. We don’t know exactly who the perfect patient is for this test. The technology is amazing. It’s close to magical to be able to sequence more than 3 billion base pairs and make sense of that in just a couple of days. But who it’s most appropriately targeted for, right now, with our experience of the people that we have helped, I would say -- I’m a neonatologist, so I speak in terms of babies. But an infant that is critically ill has a high acuity and is not responding in the typical way you would expect for an infant with their presentation, and in whom the team feels there’s likely an underlying genetic diagnosis. In a select population like that, we found that we can get a diagnosis with rapid whole-genome sequencing in around half of those cases. But if you this test in a broader population, less ill children, less acute presentation, we’re not exactly sure if there’s certain presentations that would be more well suited for this test than others, and that’s one of the things we’re trying to figure out.
Dr. Smith: Tell us about NSIGHT, the Newborn Sequencing in Genomic Medicine and Public Health Study.
Dr. Petrikin: Certainly. This is a NIH-funded, multi-center trial that is trying to figure out the most appropriate use for rapid whole genome sequencing or whole exome sequencing, which is related in the care and screening of infants. It’s broad and it’s a lot of terminology, but there are four main sites and a couple of secondary sites. And we’re all looking at different aspects of using this technology in the care of children. At our site in Kansas City, we are trying to determine the answer to your earlier question on which babies is this test best suited for, does it make a difference in their care and in their outcome, and how should clinicians use this test in the future if it becomes readily available.
Dr. Smith: That’s an interesting question, isn’t it? Here you have an ability to sequence the entire genome in a critically ill neonate. The question becomes, how is that then applied to the treatment, and what kind of outcome might you see? That is a part of this NSIGHT study, looking at who’s the appropriate patient and what outcome might come from this type of application, correct?
Dr. Petrikin: That’s absolutely correct. That’s the part of the NSIGHT trials that I’m most involved with. I guess I need to mention that there’s three segments to the trials. One involves advances in the pure technology and ability to interpret all of these data, which I leave to the magicians, our bioinformatics folks. There’s a third segment that is really investigating the ethical issues involved with getting this information and data and what do you with it and what do you report back. The part I mentioned is part two, and that is how do we use this information. How do we select patients? And does it make a different in their care and then outcome. We think it will. We think it should. But can we prove that? And can we more finely target which patients this would be most appropriate for?
Dr. Smith: What do you think is the future of genetic testing? Now that we’re able to sequence a genome so quickly, where are we going with all this?
Dr. Petrikin: That’s a great question. I sometimes fall back on an analogy from The Jetsons. Growing up watching The Jetsons, they had flying cars. And I remember thinking, “Well, I want my flying car. Where is that?” And I feel like genomic medicine hasn’t lived up to the expectations from the early 2000s, when we finished the rough draft of the human genome. We’re still waiting for the genomic version of a flying car. Where is our tricorder? Where is our ability to just rapidly target medicine informed by an individual’s particular genomic sequence and epigenetic changes? And I don’t think we’ll ever going to get flying cars, but that’s not my area. I do think precision medicine really is right around the corner. What I mean by that is -- and this is my opinion. I just speak for myself. I think that we’re not far off from having that test to our own genomes readily available on something not much different than a thumb drive. And we will seek medical care with a set of symptoms and signs, and hopefully providers will be able to take those symptoms, informed by our own individual genome, and make treatment recommendations that are most optimal for us as individuals. I think that’s the future, and I really don’t think it’s that far away.
Dr. Smith: Well, you’re not alone, Dr. Petrikin. That’s obviously the best way to treat somebody is to know exactly what it is they have, what exactly it is they need, what drugs are going to work. That’s all where the genetic testing comes in. It’d be precise and personalized, right? I think that is the wave of the future. It’s exciting, and you’re right in the middle of it. That must be awesome. Dr. Petrikin, I want to thank you for coming on this show. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Mike. Have a great day.
Genomics of Newborns: The Value of Rapid Genetic Testing in the NICU
Dr. Michael Smith (Host): Welcome to Transformational Pediatrics. I am Dr. Mike Smith, and our topic is Genomics of Newborns: the Value of Rapid Genetic Testing in the NICU. My guest is Dr. Josh Petrikin. He’s the director of Saint Joseph’s Help Center Nursery and serves as director of Neonatal Genomics at the Center for Pediatric Genomic Medicine at Children’s Mercy. He’s also the assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine. Dr. Petrikin, welcome to the show.
Dr. Josh Petrikin (Guest): Thank you. It’s a pleasure to be here.
Dr. Smith: Based on your bio, you’re a very busy man, aren’t you, Josh?
Dr. Petrikin: Well, it feels like it, yes.
Dr. Smith: Let’s start with a real simple question. What exactly is rapid genetic testing?
Dr. Petrikin: Sure. Well, standard genetic testing is the sort of thing that is still common today but that we’ve come to expect from the last 10 years or so is usually sequencing of one particular gene using standard Sanger sequencing. Not be too technical about it, but sanger sequencing is how we originally sequence the human genome, and that was a project that took more than a decade and billions of dollars. It’s very accurate but relatively slow. And as anybody that’s sent away gene panels or particular genetic testing is that you get results in weeks to months, sometimes six months or more. So, rapid genetic testing is really anything faster than that. And more specifically, what we’re able to do and are investigating here in Children’s Mercy Kansas City is rapid whole-genome sequencing, where we have the ability to sequence the entire genome of a patient, do the actual sequencing and interpretation in as short as 50 hours, and we’re actually pushing that to see if we can get it to about 24 hours.
Dr. Smith: That’s pretty impressive, right? That’s pretty amazing considering that at one point, as you mentioned, it could take weeks to get a result. Who actually should get this done? What kind of patient are we talking about here? And what’s the end goal here? What’s the value of it, really?
Dr. Petrikin: Sure. That’s an excellent question. It’s an excellent question because we don’t really know the answer yet. We don’t know exactly who the perfect patient is for this test. The technology is amazing. It’s close to magical to be able to sequence more than 3 billion base pairs and make sense of that in just a couple of days. But who it’s most appropriately targeted for, right now, with our experience of the people that we have helped, I would say -- I’m a neonatologist, so I speak in terms of babies. But an infant that is critically ill has a high acuity and is not responding in the typical way you would expect for an infant with their presentation, and in whom the team feels there’s likely an underlying genetic diagnosis. In a select population like that, we found that we can get a diagnosis with rapid whole-genome sequencing in around half of those cases. But if you this test in a broader population, less ill children, less acute presentation, we’re not exactly sure if there’s certain presentations that would be more well suited for this test than others, and that’s one of the things we’re trying to figure out.
Dr. Smith: Tell us about NSIGHT, the Newborn Sequencing in Genomic Medicine and Public Health Study.
Dr. Petrikin: Certainly. This is a NIH-funded, multi-center trial that is trying to figure out the most appropriate use for rapid whole genome sequencing or whole exome sequencing, which is related in the care and screening of infants. It’s broad and it’s a lot of terminology, but there are four main sites and a couple of secondary sites. And we’re all looking at different aspects of using this technology in the care of children. At our site in Kansas City, we are trying to determine the answer to your earlier question on which babies is this test best suited for, does it make a difference in their care and in their outcome, and how should clinicians use this test in the future if it becomes readily available.
Dr. Smith: That’s an interesting question, isn’t it? Here you have an ability to sequence the entire genome in a critically ill neonate. The question becomes, how is that then applied to the treatment, and what kind of outcome might you see? That is a part of this NSIGHT study, looking at who’s the appropriate patient and what outcome might come from this type of application, correct?
Dr. Petrikin: That’s absolutely correct. That’s the part of the NSIGHT trials that I’m most involved with. I guess I need to mention that there’s three segments to the trials. One involves advances in the pure technology and ability to interpret all of these data, which I leave to the magicians, our bioinformatics folks. There’s a third segment that is really investigating the ethical issues involved with getting this information and data and what do you with it and what do you report back. The part I mentioned is part two, and that is how do we use this information. How do we select patients? And does it make a different in their care and then outcome. We think it will. We think it should. But can we prove that? And can we more finely target which patients this would be most appropriate for?
Dr. Smith: What do you think is the future of genetic testing? Now that we’re able to sequence a genome so quickly, where are we going with all this?
Dr. Petrikin: That’s a great question. I sometimes fall back on an analogy from The Jetsons. Growing up watching The Jetsons, they had flying cars. And I remember thinking, “Well, I want my flying car. Where is that?” And I feel like genomic medicine hasn’t lived up to the expectations from the early 2000s, when we finished the rough draft of the human genome. We’re still waiting for the genomic version of a flying car. Where is our tricorder? Where is our ability to just rapidly target medicine informed by an individual’s particular genomic sequence and epigenetic changes? And I don’t think we’ll ever going to get flying cars, but that’s not my area. I do think precision medicine really is right around the corner. What I mean by that is -- and this is my opinion. I just speak for myself. I think that we’re not far off from having that test to our own genomes readily available on something not much different than a thumb drive. And we will seek medical care with a set of symptoms and signs, and hopefully providers will be able to take those symptoms, informed by our own individual genome, and make treatment recommendations that are most optimal for us as individuals. I think that’s the future, and I really don’t think it’s that far away.
Dr. Smith: Well, you’re not alone, Dr. Petrikin. That’s obviously the best way to treat somebody is to know exactly what it is they have, what exactly it is they need, what drugs are going to work. That’s all where the genetic testing comes in. It’d be precise and personalized, right? I think that is the wave of the future. It’s exciting, and you’re right in the middle of it. That must be awesome. Dr. Petrikin, I want to thank you for coming on this show. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Mike. Have a great day.