Transcription

• Stevon Burrell

  CAP Today answers your top lab questions, a new roundtable helps international pathologists navigate U.S. visa pathways, and exploring next-generation sequencing. Coming up next. This is the Path News Network Daily Edition, powered by the College of American Pathologists. I'm Stevon Burrell. It's Thursday, November 13th, and here are the latest headlines. Got questions about CAP accreditation checklist requirements? Or when to use citrate tubes for platelet counts? CAP Today's latest Q&A column breaks it down. The feature offers practical guidance straight from CAP experts, covering how the college handles accreditation inquiries, the science behind EDTA-induced platelet clumping, and how labs can interpret checklist requirements without compromising workflow. CAP Hematology Clinical Microscopy Committee member, Dr. Daniel Dees explains, quote, If all indicators point to an accurate EDTA count, then performing a citrate count typically is not warranted. Find out more by visiting the link in the show notes. And, embarking on a career in pathology in the U.S. can be complex, especially when it comes to understanding your visa options. On December 9th, the CAP hosts a special roundtable to help international pathologists and medical graduates navigate visa requirements for training, research, and employment. Moderated by Dr. Neha Varshney, the session will guide attendees through the sponsorship process, renewals, and strategies to overcome common visa challenges. It's an empowering opportunity for early career pathologists to gain clarity and confidence in their professional journey. Details and registration are available in today's show notes. As we enter another winter holiday season, experts say COVID is still part of our lives and testing remains one of our best tools. Dr. Daniel D. Rhoads, chair of the CAP's microbiology committee, tells Today.com, quote, a PCR test detects the actual genetic material of the virus and involves a step that amplifies the presence of any material that might be there, which means it can detect a smaller amount of the virus. He compares the test to hearing a whisper through a microphone. PCR amplifies faint signals while rapid antigen tests only pick up louder ones. If you test negative but still feel sick, experts recommend testing again a day later. COVID may be quieter this season, but vigilance and smart testing can still make all the difference. For more on COVID testing tips and timing, visit the link in today's show notes. And finally, next-generation sequencing continues to reshape genomic medicine, and the CAP's latest proficiency testing programs are helping laboratories stay ahead. These offerings, covering germline, solid tumor, hematologic malignancy, and in silico bioinformatics testing, strengthen accuracy and consistency across the field. Joining me to discuss the programs and their impact is Dr. Neil Lindeman. Chair of the Molecular Oncology Committee, Dr. Lindeman, the CAP recently expanded its next-generation sequencing proficiency testing menu. Why is the development of this program important, and how does it address emerging scientific or clinical needs?

• Dr. Neil Lindeman

  Molecular oncology is a relatively new field, and it's grown a tremendous amount in the last two decades, basically since about 2004, 2005. There are scores of medications that cannot be given without understanding a specific genetic change in a specific cancer type. It's part of the FDA labeling in the United States, it's part of labeling in other countries, and it's just good medical science. You can make an individual test for every one of those things, in which case we would have hundreds of different tests that we ran. We can do them all with one. And so next-generation sequencing is that technology. that enables you to detect both small alterations and large ones across dozens of genes, hundreds of genes, every single gene. My whole genome sequencing, the whole scope of the genetic complement of a person, which is called their genome. And so that technology, which was a research method about 15 years ago, and was unproven and innovative, is now standard of care and being used. all over the place, in small hospital labs, in private commercial labs, and in big academic centers as well. But since all of these tests are used to determine therapy, and the field has evolved literally in 10 or 15 years, it's not yet matured to the place where a lot of other tests are. Different centers have developed them differently. And so more than ever, more than anywhere, proficiency testing and quality assurance is needed because different tests in different centers, even for the same markers, might not get the same results. So that's why the NGS portfolio that the CAP offers for proficiency testing is growing rapidly.

• Stevon Burrell

  How do these NGS programs help laboratories strengthen quality, consistency, and accuracy when interpreting genomic data?

• Dr. Neil Lindeman

  Because a lot of these tests are still internally developed, but there are commercial products on the market now. Not only is the analytical chemistry part of the test somewhat variable from place to place, but the interpretation and the data analysis can be quite variable. I like to say, you know, each sample that I run my next generation sequencing panel gives me 20 million individual sequences of DNA to read. These two eyes cannot read 20 million pieces of information, right? Just, just, and I'm used to using a microscope, but it won't work. And so we need essentially computer tools to process that data into something that we can interpret. That's called a pipeline. And it's a bunch of sequential computer programs. There's not one program in a pipeline. It's, you know, a dozen or more. And they refine that, if you will, raw sequence data into something that these two eyes can actually make some sense out of and hopefully a little bit of brain behind the eyes. But all the pipelines are different. And so even two identical chemistry systems doing the same assay with the same sample even, if they have different pipelines, which are much less standardized than the chemistry is even, you can get different outputs. Having some external comparison system like the PT system, where I see what other labs around the country are getting, helps me understand, do I have a problem or not, or a limitation or not with my pipeline that I need to address. And so I think it's actually really important to be able to make sure that when I'm sending back to my patients and their providers is accurate.

• Stevon Burrell

  The CAP's Ensilico bioinformatics programs take a different approach to proficiency testing. Can you explain what these programs are and why they're significant for advancing precision medicine?

• Dr. Neil Lindeman

  So I alluded to it with the last answer from building up to it. There are really two components to this. There's the chemistry piece that generates sequence files that are raw and need to be refined, and then there's the pipeline that refines them into what is eventually going to get put in the report or taken out of the report or edited in some way. And each of those impacts the quality of the final product. The only practical way to test all of the scenarios that are needed to make sure that the pipeline is working properly. involved generating data files as if they came from a true chemistry sample that was tested and then running those through the pipeline. There's a biomarker that's important for giving immune checkpoint inhibitors in cancer. What they do is they unlock the immune system to recognize a tumor as foreign and then use the body's immune system to destroy the tumor almost as if the tumor was an infection. To engineer that in a lab is crazy hard because it's a pattern of injury across the 3 billion, 3 billion with a B, bases in every cell. And you have to put that pattern at random spots. But then if I'm going to give that sample to everyone, it's got to be the same for everybody. And it's just chemically impractical. So either I can get a cancer sample that actually has mismatch repair deficiency, but those are hard to get, but I can simulate it with a computer file. Okay, I can write a program that will create electronic mutations in a data file that match the pattern I want to see and then give that file back to all the labs. And so in silico PT is needed in order to identify these kinds of biomarkers that are not simple to engineer.

• Stevon Burrell

  And finally, before we close, do you have any final thoughts on the future of next generation sequencing and the role of in silico programs in supporting laboratories and genomic medicine?

• Dr. Neil Lindeman

  So one of the challenges with the in silico PT is that each lab needs to have a computer scientist basically in order to to use it. There's two approaches. One is their standard commercial systems. There are assays that are manufactured by companies. They make output files. We have a process to receive the common ones, mutate them and send them back. But the companies particularly in the world of FDA, and FDA systems are locked. They're closed. So one of the things about an FDA system is they don't want the labs tinkering with it and changing it. But in order to get those intermediate files out, mutate them and put them back, you have to unlock it. So we had a series of meetings actually with FDA, believe it or not, to try and explain to them, you know, what we were doing and to see if... they might consider encouraging the companies to take a different view and that didn't work. So then you need people who are just going to like hack the code. Or you have assays that were just developed outside of FDA by individuals that happen to have a good computational biology team that's capable of doing that. It's not a trivial thing to do. Not every place has someone who can pull that off. Certainly if we believe next generation sequencing is going to be done in every, you know, hospital, in every clinic in America, like that's a unique skill set. So one of the problems with the in silico for the future is we just don't have enough people with the right skills to implement it. And so either the systems have to change to make it easier to implement, or we have to grow a generation of people that have the skills to do it. Or I guess we can find a way somehow to make it easier. But I do think it is the only viable solution to scaling the PT that we need for the different use cases of next generation sequencing without, you know, harvesting cancers. And I mean, there's all sorts of rules about that people, you know, they have their tumor out, they don't want. It's going to someone else that's going to sell it and start using it. That's just not the point of it up here. So it's hard to get the real samples.

• Stevon Burrell

  That's all we have for today. You can find us on Apple Podcasts, Amazon Music, or Spotify. Subscribe on your favorite platform. Look for more news like this in our weekly newsletters, published every Tuesday and Thursday. We're back tomorrow at 5 a.m. Eastern with more CAP News. For the Daily Edition. I'm Stevon Burrell. Have a great day!