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Q&A: Richard Scheuermann on JCVI's Informatics Efforts, New Focus on Personalized Medicine

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Richard Scheuermann.JPGEarlier this summer, Richard Scheuermann was tapped to serve as the director of informatics at the J. Craig Venter Institute, taking charge of the institute’s informatics programs at its campuses in Rockville, Md., and San Diego, Calif., and managing a staff of 70.

Scheuermann officially took the helm at JCVI on May 1, joining the institute from the University of Texas Southwestern Medical Center where he was a professor in the pathology department. He also held a number of academic administrative positions at the university, including director of its biomedical informatics division; co-director of its division of translational pathology; and director of the university's Tissue Procurement Resource. He has developed computational methods for use in gene expression microarrays, biological networks, ontologies, flow cytometry, and comparative genomics analysis for immunology and infectious disease studies.

BioInform spoke with Scheuermann this week to discuss JCVI’s current and future informatics efforts, which will include the development of software to support personalized medicine. This is a new area for the institute, which has historically had a more research-centered agenda.

An edited version of the interview follows.


To start off, could you please give me a sense of the scope of your responsibilities at JCVI as its director of informatics?

There are two things that I’ll be doing here. First, I do have a pretty active bioinformatics research program. I’m the principal investigator on several National Institutes of Health-funded projects and I’ll be continuing the work on those here at JCVI. They largely revolve around viral infectious diseases and immunology-related bioinformatics research.

Second, as the director of informatics, I’ll be working to coordinate the global informatics program at JCVI. Currently, there are about 70 people who fall under the category of informatics; some of them are faculty-level investigators, and some are staff. We have an opportunity with me coming on board as the director to reorganize the way that informatics is being approached at JCVI. My goal is to establish a more research-oriented informatics environment where we foster new informatics methods development, in addition to providing collaborative informatics support services.

Prior to joining JCVI, you were at UT Southwestern Medical Center. What prompted you to make the move from academia to the not-for-profit research realm?

I had been on the faculty at UT Southwestern for 20 years and I was a tenured professor. We had developed a very successful bioinformatics program and I felt like bioinformatics had grown to become a critical component of the modern research that was being funded by institutions like NIH, that were really trying to promote team science, multidisciplinary research and high-throughput data generation and analysis.

But I guess I ended up getting a little frustrated that many academic institutions were not recognizing the value of bioinformatics as a research discipline and were not putting significant effort and resources into building informatics research programs.

So, in thinking about finding an environment where informatics was valued and where it was a critical component of the vision of the institution, JCVI was an obvious candidate. From its inception, informatics has always been a key part of the research activities that have been going on here. I felt like it would be a great environment to be in because JCVI recognized the value of the work that we were doing.

Is the lack of interest in informatics something that’s unique to a few academic institutions or is it a more widespread phenomenon?

My sense is that UT Southwestern is not unique in that regard. There has been a paradigm shift in how research is being approached and I think many institutions are struggling with informatics in many different ways. First of all, ideally you would want to have a critical mass of people who are doing bioinformatics work, but the number of people who have that kind of training is pretty limited. It’s getting better — there are more bioinformatics training programs out there every day — but it's not mature enough where you have a lot of senior investigators who have that kind of background. So there just aren’t that many people out there for academic institutions to recruit.

The other thing is that many academic institutions are also struggling with trying to quantify the measures of success for faculty who are doing bioinformatics research. The traditional way that they look at a faculty member and consider them for promotion or tenure is to determine how many grants they have been able to get where they are the principal investigator. That’s the key metric in an academic environment. But in bioinformatics, it’s actually very challenging to get an NIH grant just to do bioinformatics work. What you frequently see is the people who are successful in bioinformatics are part of a team where bioinformatics is a big part, but when those grants go in for award, it tends to be the experimentalist who ends up being the PI on the grant, not the bioinformatics person, even though they are a critical part of the team. A lot of academic institutions are struggling to figure out how best to judge the performance of a bioinformatics faculty member.

Do you have any suggestions for possible solutions to these issues?

I think that the promotions and tenure committees will have to learn how best to take these factors into account. They have to recognize the value of contributions to multidisciplinary research and the reality that it’s difficult to get funding to do bioinformatics research in and of itself. I think there has to be an educational process that these committees go through to become comfortable with what the bioinformatics discipline is all about and what is a good measure of success.

Another possible solution is to have more funding opportunities for doing purely bioinformatics research. There are a few of those opportunities out there, but there are not a lot, and they are very competitive.

Let’s come back to your new role at JCVI. You officially stepped into the role on May 1. What have you been up to in the last three months?

I definitely hit the ground running. One of the new areas that we have an opportunity to go into, which is a little new for JCVI as an institution, is in the area of genomics-based personalized medicine. I was in a pathology department at UT Southwestern and I am pretty familiar with the clinical and translational research environment. One of the things that attracted me to JCVI, and specifically to the campus in San Diego, was the opportunity to be able to interact with the medical school at the University of California, San Diego.

I had a chance to meet with the dean of the UCSD medical school and get a sense for their vision for where they want to see their institution head. There was a nice synergy between what I thought JCVI could be doing and what the medical school was thinking about doing. It revolved around this notion that as sequencing costs are dropping dramatically, in the very near future we have an opportunity to apply whole-genome analysis in a clinical setting. The fact that JCVI has extensive experience in high-throughput sequencing and in the informatics necessary to interpret that data, and that UCSD has a terrific medical school with state-of-the-art clinical and translational research, if we put these two institutions together, we would be able to be leaders in this emerging field.

Virtually the day that I started here, there was an NIH [request for applications] that was released to specifically support research in this area - the Clinical Sequencing Exploratory Research program. The program was designed to support projects that will translate next-generation sequencing technologies into clinical diagnostics. The day that I started, I worked on pulling together all of the relevant people and both institutions who would be necessary to put a proposal of this nature together. That has kept me pretty busy over the last three months.

Why is JCVI just now looking into genomics-based personalized medicine?

Historically JCVI has been one of the leaders in genome sequencing for bacteria and viruses and other organisms of that sort. Obviously, they’ve also been a leader in the human genome sequencing project. They haven’t been that involved in looking at human sequence variation and how it relates to disease etiology and pathogenesis. I think we are now positioned to really start tackling those questions and identifying the correlates between sequence variation and disease phenotypes, and then to start incorporating this knowledge into personalized medicine and patient management strategies.

Institutions like JCVI hire good people that have good ideas and let them decide what research they want to pursue. I think that’s partly what has happened in my case. We had common interests in viral infectious diseases through our Bioinformatics Resource Center projects and JCVI’s Genome Sequencing Center program, but, in addition, I’ve had a longstanding interest in autoimmunity and other kinds of human diseases. There wasn’t a major research focus in these areas here previously, but they were very receptive to me bringing in some of those new ideas and developing that kind of program here; they were happy to provide me support for doing that.

In line with your new focus, are you planning to do any software development?

Yes. I’m a big proponent of open source software. We develop a lot of algorithms, and we make those algorithms freely available for the community to use. In some cases we take the extra step and try to convert algorithms into software to make it even easier for the average experimentalist to be able to use some of these methods. I plan on continuing that work, and certainly in the proposal that we submitted, there are some novel algorithms that would be required for us to be able to address the clinical utility of sequence variation information.

Are you hiring?

Yes. In fact we are recruiting at both the faculty and staff levels. Because I want to build human disease-focused informatics research here, I want to recruit some faculty who have those kinds of interests.

I understand you brought some members of your lab with you from University of Texas. You talked a little bit about the research you are involved in at the start of our conversation but can you go into a bit more detail?

Our infectious disease work is focused on a program that’s funded by the National Institute of Allergy and Infectious Disease called the Bioinformatics Resource Centers for Infectious Diseases. They fund five of these BRC programs, which are intended to capture and integrate data about different categories of human pathogens. I am the PI on two different BRCs, both related to human viral pathogens. One of them is focused exclusively on the influenza virus. They wanted to put special emphasis on providing a resource to support information about flu since it is a major concern based on its obvious pandemic potential.

Then we have another BRC that basically covers the other human pathogenic viruses including things like Ebola and West Nile virus, pox viruses, hepatitis C, Dengue, and SARS coronavirus. The idea with these BRC resources is that we want to capture different kinds of data about those viruses, bring them into a single resource and then integrate the data with data analysis tools to do comparative genomics analysis and things like that.

In the area of immunology, historically, I’ve had some informatics projects supported by the NIH to do that work, but I had to leave some of those behind when I left UT Southwestern. That’s an area that we are going to be trying to rebuild here. One of the tools that immunologists use pretty routinely is flow cytometry to analyze different cell subsets in mixtures and see how they respond in different ways. My group has been involved in developing algorithms that can automatically identify cell populations in flow cytometry data. This is kind of a new field in bioinformatics and we’ve been successful in developing some of these methods. That’s an area that we are going to be continuing to work on here.

Finally, are there any specific things you’d like to have accomplished by year’s end?

One thing that is a relatively new area for us in the infectious disease work that we are doing is in the area of host-pathogen interactions. Historically we have focused on data and analysis related to genome sequences of the pathogen. We are starting to emphasize support for data that will provide a better understanding of host-pathogen interactions. How does the host respond to a viral infection? What genes are upregulated or downregulated in the host in the course of an infection? What host proteins and genes are required to support viral infection and what genes and proteins are helping to inhibit viral replication?

We interact with a lot of research groups that are generating this host factor data and one of the areas that we are really pushing this year is to come up with good ways of bringing that data together, making it available through our resources, developing novel methods for analyzing host factor data and visualization tools for looking at pathways and networks of host factor genes and proteins and how viruses are interacting with those networks.

Another big research area of focus at the JCVI is in metagenomics and microbiomes. There are a couple of examples of that … There is the global ocean survey that they have been involved in where they get samples from different locations around the world and try to understand the complexity of the different organisms that reside in these aquatic communities using metagenomics as a way of getting sequence information about many of these organisms that are not cultureable. Metagenomics is also being applied in the area of human disease, looking at the human microbiome through metagenomics analysis and how it might be involved in disease pathogenesis.

JCVI has turned out to be an incredibly stimulating environment to pursue our broad interests in bioinformatics research. Stay tuned for more exciting discoveries to come out of JCVI!

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