Episode 62: QIIME in if You’ve Heard This One Before

Karie Dozer: [00:00:04] What do a video game designer and a researcher at TGen have in common? Perhaps quite a lot, especially if the programmer has an interest in science. I'm Karie Dozer and this is TGen Talks. As researchers and physicians study how to reduce the risk of deadly disease. A great deal of attention is now being focused on the microorganisms that live in and on our bodies. Now more than ever, we are learning that a so-called healthy gut is important not only for feeling good, but for fighting and treating diseases like cancer. Today on the podcast, we'll meet a TGen scientist whose research into the human microbiome actually began in a computer science lab. Dr. Greg Caporaso is a newly appointed bioinformatics and at TGen North and his experience in the computer science world lends itself to managing and analyzing the vast amount of information researchers now have about the human microbiome. Dr. Caporaso, thanks for taking the time to talk. How are you? [00:01:05][61.3]

Dr. Greg Caporaso: [00:01:05] I'm doing great. Thanks for having me. [00:01:07][1.4]

Karie Dozer: [00:01:07] Tell me a little bit about what you do here at TGen. [00:01:09][1.9]

Dr. Greg Caporaso: [00:01:10] I work on studying microbiomes, which are communities of microorganisms, and those can live either on the human body, in the human body. That would be the human microbiome. And I also work on environmental microbiomes. So things we might find out in soil or in water. And my niche with all of this is the computational aspects of microbiome research. And so I work as a bioinformatician rather than sort of your typical thought of biological researchers working in a laboratory. Most of us are working at computers trying to make sense of all the data that's being generated in the laboratory and turn that into new information and new knowledge. I view myself as a scientist, and the tools that I use to do my science are computers. [00:01:55][45.3]

Karie Dozer: [00:01:56] Tell me the path that got you to this place, because that sounds like an awful lot of training. What did it take to get you to this place? [00:02:02][6.3]

Dr. Greg Caporaso: [00:02:03] So I've loved computers since I was a kid. I was lucky that back in the eighties when I was growing up, my parents had a home computer that they used for their work, and I spent some time around then and in high school doing computer graphics. And so again, like pretty early on for those kinds of fields, but had a really awesome teacher in high school who had set up a computer graphics lab in like the early 1990s, which was really cutting edge for high school at that time. And I initially did an undergrad in computer science and went and worked in industry for a little while and I was working for a company that was building software for doing server and database monitoring and it was interesting, I gained a lot of good skills, but I didn't find it very fulfilling and I was sort of interested in applying computing in science and wasn't really sure where to go with that. I started taking some classes at night at C.U. Boulder, started taking some biology classes, thinking maybe I wanted to go into medicine. And so I started taking like the pre-med classes, but then got interested in the research side of all that and realized how critical computing was to making advances in biology because biology was increasingly becoming a data-intensive science. This was around the time the human genome was first sequenced when I was first getting into this. And so it was clear that we were going to need some new tools to analyze all of the data that was being generated. And so I ended up taking a few more classes and getting a second undergraduate degree in biochemistry at the University of Colorado, and so ended up doing a Ph.D. in biochemistry. But really the work that I was doing was very bioinformatics focused at that time, and so my Ph.D. work really was bioinformatics and then ended up moving back up to Boulder to do a postdoc in a microbiome and bioinformatics lab at CU Boulder. And that was when I sort of got into microbiome research. The lab that I worked in had done some early methods development to facilitate their own microbiome research, and they were interested in starting to move the tools that they had been developing into a form that could be accessible to other researchers around the world. And so that was kind of where I fit in. I had a background in computer science and software engineering, and so I got involved there as part of a team that was working to make those computational methods for microbiome research more generally accessible. [00:04:54][170.9]

Karie Dozer: [00:04:55] So why microbiome? Why that particular field? [00:04:58][2.6]

Dr. Greg Caporaso: [00:04:58] Well, yeah, I sort of initially fell into it through the bioinformatics side. And because this was a microbiome lab that needed some bioinformatics expertise. But I think it's just an absolutely fascinating area. And so we now know, for example, that there's as many bacterial cells in and on the human body as there are human cells. And so this, you know, effectively equates to us almost having a whole organ that that we didn't even know about. And one thing that I find really exciting and really promising about the microbiome is that we're now starting to understand the many ways that our gut microbiome, in particular, impacts our health. But unlike your genetics, which you don't really have the ability to change in any meaningful way throughout your life, you can make changes on a daily basis that can impact the microbiome and your microbiome composition. And so I think it provides some will ultimately provide some very actionable pathways to improved health. [00:06:06][67.1]

Karie Dozer: [00:06:06] So I want to get to the gut health and what it means for our overall health and our ability to fight disease. But when let's get back to bioinformatics for a minute. Tell me what it really means and why it is so beneficial for researchers like yourself. [00:06:19][12.8]

Dr. Greg Caporaso: [00:06:20] So I, I tend to define bioinformatics as the application of the tools of computer science. So things like programming languages, databases, parallel computation, machine learning to address biological questions. So, things like understanding the evolutionary relationship between a group of organisms or say, for example, to go back to the microbiome, understanding if or how, say, a certain treatment or certain diet change impacts the community of microorganisms that are living in your gut. And it's absolutely critical to biological research now, in large part because the tools that biologists are using. So, for example, a DNA sequencing instrument generates enormous quantities of data. And so better computational tools are essential for turning that data into new information and new knowledge. [00:07:20][60.1]

Karie Dozer: [00:07:21] In addition to your work here at TGen, you spend a lot of time at Northern Arizona University and you lean on your computer science background in your work there. You've been instrumental in developing something called QIIME, QIIME 2, to be exact. What is QIIME? What does it stand for and what do you use it for? [00:07:38][17.5]

Dr. Greg Caporaso: [00:07:39] I mentioned earlier that I was doing a postdoc in Boulder working on making some microbiome software more accessible, and that ultimately became what we call QIIME 1, or really at the time we just called it QIIME. And so I worked on that for about a year while I was at C.U. Boulder, and then I brought that project with me to Northern Arizona University when I took a faculty position around 2011. And at that point the project sort of became a collaboration between my new lab at NAU and then the group that I had been working with at University of Colorado at Boulder. We continued developing QIIME 1 for a few years after that, and during that time it was becoming increasingly popular in the field. So microbiome research was really starting to take off. The technologies that were being used to generate the data were changing such that the data is becoming much cheaper and which in turn meant that we were getting a lot more of that. And so we began teaching a lot of change workshops. We were teaching them around the world to grad students, postdocs, faculty members, physician scientists, really many different people were interested, and those folks were working on either the human microbiome, environmental, microbiology, food, microbiology really, fields we had never really thought about when we started developing it and then interacting with thousands of users through those events. So we did a lot of in-person teaching events. And then through an online forum. We began to get ideas about things that we needed to do at the platform to make it more accessible, to make the underlying bioinformatics more reproducible, and to just generally enable sort of the next stage of advances in the field. And when we started putting all these different things together that we needed to do with that, we realized it just wasn't possible with the way that we had architected the original system. And so around 2015, we started prototyping some new tools. And ultimately ended up basically scrapping the entire QIIME 1 code base and rebuilding from scratch and that's what became QIIME 2. [00:10:11][151.9]

Karie Dozer: [00:10:11] You talk about the human microbiome and the environmental microbiome. Are those the same to the nonscientific person? Are we talking about the same thing or are we talking about vastly different organisms? [00:10:22][10.5]

Dr. Greg Caporaso: [00:10:24] There's some overlap and there's some organisms that are vastly different, and it really depends a lot on what type of environment you're looking at. The human microbiome and an environmental microbiome. They are distinctly different things, but they're closely related. The microbes that we encounter in the environment impact the composition of the human microbiome. And I think we may find in the future that the composition of the human microbiome or other animal microbiomes are impacting the composition of, say, soil microbiomes. [00:10:58][34.7]

Karie Dozer: [00:11:00] Let's get back to the gut health question, because it's sort of become a buzzword. How much do we know about gut health? You touched on the fact that we're really just beginning to understand how gut health really affects our overall health and our ability to fight disease. What do we know and how much is there left to learn? [00:11:17][17.4]

Dr. Greg Caporaso: [00:11:18] We are just scratching the surface. That's how I would think about it. We've had the technologies that we need to study microorganisms in, in great detail, only for about 25 years. They're the same technologies that were used to sequence the human genome initially. And so in that time, we have done a lot of work. Initially, first, just describing microbiomes, understanding, for example, how diverse the human gut microbiome actually is. And now we're starting to get to a point where we're understanding how microbiomes change over time, what factors might impact how a microbiome is going to change over time. And even in some cases, we're starting to think about, and we're starting to learn about, how to directly impact human health by altering microbiomes. [00:12:12][53.4]

Karie Dozer: [00:12:13] Is that something that when you talk about this being relatively new in the last 25 years or so, is that something that most, you know, doctor-patient level conversations are those kind of conversations being affected by this information that you're gathering in this data and this new knowledge? Or do we still have a long way to go in terms of translating this data and this information to a patient at the bedside? [00:12:35][22.0]

Dr. Greg Caporaso: [00:12:36] I think to some extent it's starting to impact those conversations. Mostly, I would say, you know, more in the case of specific disease states and less in the context of just sort of regular checkups with a physician at this point. But, for example, it is already having a massive impact on how we treat Clostridium difficile infections. For example, just in December of 2022, there were two FDA-approved treatments for Clostridium difficile infections that are directly targeted at altering the recipient's gut microbiome. And those are both fecal microbiota transplant protocols. It has very high success rates for treating recurrent Clostridium difficile infections. There are a few clinical trials that are currently in progress right now that are focused around cancer treatment protocols and integrating fecal microbiota transplant. [00:13:36][60.2]

Karie Dozer: [00:13:37] What could that possibly have to do with someone who's been diagnosed with cancer? [00:13:41][3.7]

Dr. Greg Caporaso: [00:13:42] That's a great question. Probably the highest profile work that's being done in this area right now is using fecal microbiota transplant as part of a cancer treatment protocol. And so, for example, you may have heard of immunotherapy for treating cancer. There's been some work recently that has shown that the composition of the gut microbiome impacts how effective immunotherapy is at reducing tumor size. And this makes sense because there's constant interaction between the gut microbes and the immune system. And so what some research teams are now looking at is trying to transplant fecal microbes from individuals who have responded to immunotherapy into patients who have not yet responded to immunotherapy. You mentioned the healthy human microbiome. And that's really a very interesting topic right now, because what we're really beginning to understand is there's not there's no such thing as the healthy human gut microbiome. It's a huge spectrum of healthy microbiome states. And so trying to understand what's common across those states and what are common characteristics of a healthy-associated microbiome is a very active area of research. Different ethnic groups or different cultural groups may have differences in what a healthy gut microbiome looks like, potentially related to the types of food that they're eating. And so it's really important that we think about diversity when we are collecting human microbiome samples and trying to understand what a healthy human microbiome looks like. [00:15:26][103.9]

Karie Dozer: [00:15:27] What's an example of an area of research that you're doing right now into a particular type of cancer? [00:15:33][5.8]

Dr. Greg Caporaso: [00:15:34] So one project that I'm working on right now is in collaboration with Melissa Herbst Kralovetz and her team at the University of Arizona Cancer Center. And this is a cervical cancer project where they are looking at the human gut microbiome, the human vaginal microbiome and the endometrial microbiome, which to this point has not been studied nearly at all. We don't really know very much. We don't have very much reliable information at all about the endometrial microbiome. But it seems like some combination of these is impacting the development of cervical cancer. And so what we're working on in that project is trying to understand the microbiomes at these three different sites in women who either have cervical cancer or have other benign gynecological conditions that brought them to the hospital to enroll in this study. And one of the things that I think is really promising there is it enables us to search for earlier markers. And so if we can understand where and how these microbes may be interacting to impact the development of cervical cancer, that may give us an idea of how we can identify that earlier. [00:16:51][76.9]

Karie Dozer: [00:16:52] So is the end goal then the development of an early detection test for cervical cancer? [00:16:57][5.0]

Dr. Greg Caporaso: [00:16:58] Absolutely. And ideally, like I mentioned earlier, since the microbiome can be modified over time, ideally it's providing actionable information as well. And so we're probably not quite there yet, but maybe there are certain diet changes that you can make to set you up for healthier microbiome states. [00:17:17][19.4]

Karie Dozer: [00:17:18] That's fantastic. What have I missed? Is there something about you or your research that we haven't talked about that you want to make sure that people know? [00:17:25][7.0]

Dr. Greg Caporaso: [00:17:25] I guess, yeah. One thing that I would throw out there, you know, if there's any younger folks listening who are thinking about who are interested in biological research and trying to think about where they want to go and what their niche is, there's a lot of opportunity right now for folks who are interested in biology but understand how to work with computers. And so, for example, understand how to program or understand how to generate visualizations in ways that can help people interpret data. So tons of opportunity, tons of really great paying jobs in this area right now. And so I would highly recommend keeping an eye out for opportunities to apply programming in biological research. [00:18:12][46.9]

Karie Dozer: [00:18:13] Probably not the typical path when most people think about majoring in a computer science in college, this is not where they think they're going to wind up. [00:18:20][6.5]

Dr. Greg Caporaso: [00:18:20] Yeah, most most of the folks that I've interacted with who come into the computer science program at NAU, for example, are interested in doing things like video game programming, For example. [00:18:32][12.1]

Karie Dozer: [00:18:33] Does a good video game programmer make a good bioinformatician? [00:18:36][3.1]

Dr. Greg Caporaso: [00:18:37] Most likely, you know, there's the skills in terms of programming and software engineering are very similar. For example, most of the folks who are working on my team in staff positions, most of them come from backgrounds in computing, not from backgrounds in biology. And so by working with scientists, they can sort of pick up what they need in order to help with making advances in biology. [00:19:06][28.9]

Karie Dozer: [00:19:06] Dr. Greg Caporaso, thanks for your time today. I appreciate it. [00:19:08][1.9]

Dr. Greg Caporaso: [00:19:09] Thanks so much for having me. [00:19:10][1.1]

Karie Dozer: [00:19:11] For more on TGen's research, go to TGen.org/news. The Translational Genomics Research Institute, Part of City of Hope, is an Arizona-based nonprofit medical research institution dedicated to conducting groundbreaking research with life-changing results. You can find more of these podcasts at TGen.org/tgentalks. Apple and Spotify, and most podcast platforms. For TGen Talks. I'm Karie Dozer. [00:19:11][0.0]

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