Molecular Diagnostics

Additional Info

• Audio File:uab/ua149.mp3
• Doctors:Mackinnon, Craig Jr.
• Featured Speaker:Craig Mackinnon, Jr. MD, PhD
• CME Series:Medical Innovations
• Post Test URL:https://cmecourses.som.uab.edu/mod/quiz/view.php?id=4018
• Guest Bio:Craig Mackinnon, Jr. MD, PhD is the Division Director, Genomic Diagnostics & Bioinformatics. 
  
  Learn more about Craig Mackinnon, Jr. MD, PhD 
  
  Release Date: June 8, 2020
  Expiration Date: June 8, 2023
  
  Disclosure Information:
  
  Dr. Mackinnon has no financial relationships related to the content of this activity to disclose. Also, no other speakers, planners or content reviewers have any relevant financial relationships to disclose.
  
  There is no commercial support for this activity.
• Transcription:Melanie Cole: UAB Med Cast is an ongoing medical education podcast. The UAB division of continuing education designates that each episode of this enduring material is worth a maximum of 0.25 AMA PRA category one credit. To collect credit, please visit UABmedicine.org/medcast and complete the episodes post-test.
  
  Introduction: Welcome to UAB Med Cast continuing education podcast for medical professionals bringing knowledge to your world. Here's Melanie Cole.
  
  Melanie Cole: Welcome to UAB Med Cast. I'm Melanie Cole and today we're discussing molecular diagnostics at UAB Medicine. Joining me is Dr. Craig MacKinnon. He's the Division Director in Genomic Diagnostics and Bioinformatics in the Department of Pathology at UAB Medicine. Dr. MacKinnon, it's a pleasure to have you join us and before we delve into this heady topic, tell us how you came to UAB. What drew you to their department?
  
  Dr. MacKinnon: I joined UAB about a year ago. Previous to this, I was at the Medical College of Wisconsin and Milwaukee, Wisconsin where I had established a molecular diagnostic lab that did clinical testing on patient samples. And we also supported research for the institution where I worked. And having done that for several years and we got successful at it, my current chairman, Dr. George Neto recruited me to come down to UAB and take the existing molecular lab that had been previously set up and using my experience up in Wisconsin, expand it so that we can update our technologies and increase the number of tests that we offer for our patients here.
  
  Host: Well, thank you for telling us about that. So then give us an overview of molecular diagnostics at UAB Medicine, as well as how it relates to what we're going through right now in COVID-19?
  
  Dr. MacKinnon: Molecular diagnostics. What that essentially means, anytime you have the word molecular and a test or a field in medicine, it typically means that you're analyzing DNA or RNA. And what we're doing is looking either at changes in the sequence which would be causing mutation that could be responsible for some type of disease or process that's unhealthy to the individual or we're looking at changes in the amount of the gene that's being expressed. So when we talk about molecular diagnostics, typically what you do is you remove the DNA or RNA from either a person's cells by extracting the tissue and isolating the DNA. Or you can do it from microorganisms. Like in the example of COVID-19 testing, you're removing the RNA from the virus. Then you do some type of test which could be PCR based, sequencing based, hybridization based, and what's you're asking is a specific question, is there a mutation? How much of this gene is being expressed, how much of it is not being expressed, and so on? And you get an answer and then you take that answer and you fit it into the clinical context to get a result that the clinician can then use to treat the patient.
  
  Host: Fascinating, and an absolutely fascinating field that you're in. As a latest example of how genetic sequencing has made that leap from research labs to patient bedsides for years now and it was difficult to do an expensive. Tell us how you can now sequence with high precision and accuracy at lower costs. Tell us about that.
  
  Dr. MacKinnon: Well, the reason that genetic sequencing has become available to many patients in many institutions is due to the advances in the technology that are used to generate that sequencing data. If we think back, maybe it was 15 years ago, 20 years ago when the human genome was initially sequenced, this took thousands of people to do. It was very slow going and cost prohibitive, maybe around a billion dollars for one genome and that's because the technology that was being used back then was not scalable and it was low throughput. And in the early two thousands maybe around 2004, 2005 some commercial companies developed sequencers using a different approach called massively parallel sequencing where you could generate a lot of sequencing data in a very short time. And what this actually did in the process was created a whole new industry called bioinformatics. So once you generate the sequencing data, how do you analyze it?
  
  How do you understand it? How do you pull out the important information that's clinically relevant from the background information that is not relevant to your patient? And how do you turn that into a clinical report? So we are now at a place where a lot of commercial vendors provide tests and kits and information solutions for labs so they can get set up and running. And at UAB we've done a lot to develop our own technologies in house. We have the ability to analyze our sequencing data from the tissue that we receive, to the report that we make all in house. So these advances that make it accessible to patients now are being driven by technology that allows you to sequence more and more of a genome from either the patient or an organism at a much.
  
  Host: That's so cool. So tell us a little bit about your rapid turnarounds, Dr. McKinnon and how those are possible by your revolutionary machine Idylla. Tell us what that is and how it can allow for same day testing.
  
  Dr. MacKinnon: Rapid genetic testing is important because clinicians need to get the test results back as soon as possible. And currently with the sequencing technologies we use at its very fastest. If you have a lab that is operational 24 hours a day, seven days a week, and as soon as the sample comes in, it can enter the testing pipeline. It still takes three or four days for the result to be finalized and reported back to the clinician. So there is a need for developing ultra rapid testing and we've adopted two platforms at UAB for doing this. The first one is what you mentioned earlier and that's called the Idylla. These are instruments that are incredible in terms of rapid and ease of use. You take a piece of tissue from a paraffin block, you cut off a thin slice, about the thickness of a piece of notebook paper, put it into the cartridge, loaded onto the machine, and within two or three hours you get a result. And this can be very helpful for really small samples that are too small to test by conventional methods.
  
  And then occasionally you'll have a patient who's coming in to see their clinician that afternoon and they need to come up with a treatment plan. And because the turnaround time on conventional sequencing is so long, it's possible that sometimes their appointment is scheduled before those results from the large test come back. So you can get a, an early insight into what type of mutations the patient's tumor may have using cancer as an example, and therefore make the patient's office visit more efficient for the patient. They don't have to come back again to find out what the results are and you can even start therapy sooner than, than waiting for the result. It also gives a lab like at UAB, a competitive advantage because now we can do testing quicker than it takes to take the sample, put it in a FedEx box, send it across the country to a lab, let them do their processing, and then communicate the results back. So it helps the lab run enough testing to help them, and it provides a benefit to the patient because the results come back quicker and fully informed clinical decision making can happen more effectively.
  
  Host: That's amazing. Really the technology is amazing that you're using. So how are you expanding both your team of experts and the tests and services you offer relating to genomics diagnostics?
  
  Dr. MacKinnon: I'd mentioned that we have two methods for doing the rapid turnaround test and we'll use that as an example. I talked about the Idylla and the Idylla is just looking at one gene at a time. We now can do rapid, large genetic panels with 50, 60, 70 genes rapidly. And that helps because if you're looking for a mutation in subtle genes, you don't know which one may have the mutation. So you have to run them one after another and that can become just as long as sending it out to a reference lab. So that is one way is to take this rapid turning around testing and expanding the number of targets, the number of different genes that can be run in the same assay in parallel. And then to support that, probably the biggest effort we're making right now in our division at UAB is to expand our bioinformatics capabilities by building a large team of informaticians who can take the genetic data, analyze it appropriately, and help to interpret it for the purposes of generating a clinical report.
  
  And working in parallel with the informaticians are the systems administrators and the IT folks who get all the equipment and servers talking to each other. We're exchanging huge data files, you know, several gigabases that are not easy to move around. And so you need a really expert IT team to support that as well. So you have the pathologist, the lab staff, the informaticians and the IT staff all together make a team that allows you to go from a patient sample, that you receive in your lab to a clinical report, that goes back to the patient and their treating physician. And we try and do that as quickly as possible without sacrificing accuracy or safety for the patient.
  
  Host: Such a comprehensive approach. Dr. McKinnon, what are some goals for the Precision Diagnostics Laboratory? What do you see as future direction for molecular diagnostics at UAB Medicine?
  
  Dr. MacKinnon: Well, our future goals are to expand the scope and scale of our testing. Right now we, I would say we mostly focusing on tumors because tumors are diseases in which a patient's cell acquires mutations that allow that cell to grow uncontrollably and it forms a tumor mass and eventually it can spread throughout the body. But we want to use these same technologies, the same approaches, but apply them to non oncology problems such as pharmacogenomics. People as you know, can be given a drug and they, based on how their body metabolizes the drug, you have to sometimes alter the dosing. If there are rapid metabolizers who maybe give them an extra dose of the drug, if they're very slow metabolizers you give them less of the drug. So that you can keep the drug levels in their body in a safe range. So there's a huge amount of applications for genotyping, which means that you're looking at the different sequence variations and the enzymes that metabolize these drugs and developing a report for that patient so they can customize their gene dosage. That's a big area for the future that we're getting into. And I think there's a lot of applications at UAB for the different clinics. For example, psychiatric drugs and pain management are two areas where this would have an enormous impact right off the bat.
  
  Host: Do you have any final thoughts for other providers on what you're doing there and why your work is so exciting?
  
  Dr. MacKinnon: Well, I would just like to say that this is a huge team effort involving lots of people other than just myself. And one of the advantages of UAB I think is that it has in general a collaborative nature and everyone has a forward looking mission focused approach to patient care. So what we are doing here at UAB I think is very fortunate because the environment fosters this type of collaborative growth and this collaborative approach to treating patients. I think we're very fortunate to be here and have that existing culture in our institution. Other places that maybe difficult, more difficult if there siloed or you don't get a chance to engage with people. I'm working on areas that are related but that you may not encounter otherwise. So I think that's one of the ingredients that's helps UAB be such an outstanding medical institution and permit this type of innovative work to take place.
  
  Host: Thank you so much, Dr. McKinnon. Such a fascinating topic. Thank you for coming on and telling us about molecular diagnostics at UAB Medicine. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. And that concludes this episode of the UAB Med Cast. For more information on resources available at UAB Medicine, please visit our website at UABmedicine.org/physician. Please remember to subscribe, rate, and review this podcast and all the other UAB Medicine podcasts. I'm Melanie Cole.
• Hosts:Melanie Cole, MS