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Claire Fraser, President, The Institute for Genomic Research

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AT A GLANCE

BS from Rensselaer Polytechnic Institute and PhD from State University of New York at Buffalo.

Research interests include whole-genome sequence analysis of microbial genomes and the use of genomic-based approaches to elucidate differences in gene expression.

Hobbies include raising standard poodles.

QWhat are the ways you would say that TIGR has grown more sophisticated over the years?

AGetting more sophisticated has been an ongoing process. It’s been doing things like building gene families. So you’re now not relying solely on pairwise sequence alignments. You’re looking at a new sequence in the context of a much larger gene family where critical amino acid residues essential to the function of the proteins in that specific family can immediately be identified. That gives you much better information about whether something is a true hit or not.

All of these things — setting up the phylogenetic databases, the gene family databases, going to hidden Markov model analysis — that’s taken a lot of human intervention to build those resources. It’s an ongoing process because as new sequences become available, regardless of whether they’re microbial sequences, plant, or mammalian, those can be fed into all these existing database resources. And it’s important to do that and keep them up to date.

We consider that part of the necessary overhead to stay at the forefront of what we’re doing. That comes at a cost, but I think that the product you get out of the other end as a result is worth the investment because it means that today, I think, you can rely with a greater degree of confidence on what you get from TIGR annotation than you could four or five years ago.

QAs a percentage of your current staff, what part is bioinformatics?

ATIGR is currently about 300 people total. I would say 60 or so represent our bioinformatics group. It’s an area where I don’t think we’ve ever been fully staffed in terms of what we think we need and positions we have funded by grants. That means that everybody has had to work at 150 percent all the time in order for us to keep doing what we’re doing.

What has suffered as a result is not so much our finished product, because people are so enormously dedicated to making sure that’s the highest level. But a lot of the people on our bioinformatics staff are PhD-level scientists who came in with areas of interest that they were hoping to have a little bit of time to follow up on on their own and that’s what’s had to be sacrificed. To me that’s really a tragedy. But we just can’t find the people that we need to fill these positions.

QWhat percentage of your grant requests do you put toward bioinformatics?

AAs much as we can without adversely affecting the bottom line. That might sound like a non-answer but it isn’t, because if a grant is primarily a sequencing grant, funding agencies are truly looking at the bottom line. They say, ëSo many base pairs in the genome, so many dollars in the grant.’

We’ve had to make the choice on a few more recent grants that we’re not going to necessarily ask for all the money we think we could be justified in asking for to cover all our bioinformatics costs. If we were to do that it would skew the bottom line and regardless of whether or not reviewers come back and say, ëTIGR does a great job at producing finished, highly annotated genome sequences,’ reviewers have now been instructed, whether overtly or not, to look at the bottom line. If we’re 30 or 40 percent higher than another group because we’re presenting our fully loaded costs, we’re not going to get the grant. That’s not going to help us if we’re trying to pay for salaries for people in the sequencing core, faculty salaries, bioinformatics salaries.

QAre you aware of any efforts to take that into account in the future?

ANo, I don’t think so. I think as long as grant applications come in that don’t take that into account there’s no reason to. It’s no different from having work done on your house. Obviously it’s not always the bottom line that you take into account, but if you’re confident that you’ve got two people that can do pretty much the same job, and one comes in for a whole lot less money, I don’t know about you but Ö

QDo you get grants just for bioinformatics?

AWe do have one from the DOE for our big microbial database — the Comprehensive Microbial Resource — that was initially crafted out of bioinformatics money associated with these various sequencing grants. We had enough of a start on this to tantalize the folks at DOE. They are now funding that as a standalone bioinformatics activity.

That’s a good precedent and that’s what we need going forward. One of the things we appreciate, and I think others do as well, is there has not been enough money directed towards building databases and building tools. While we were able to get by with what we had when we were just doing sequencing, we were looking at basically databases of gene and protein sequences.

If we now want to start layering functional information from microarray analysis and proteomic analysis on top of that, existing databases are not going to be robust enough. For some of these, it’s almost easier to go back to the drawing board and build something from scratch than it is to continue to put band-aids on existing databases. That doesn’t mean that any of the databases that are out there now are bad, it just means that at the time they were set up it was very difficult for anyone to look into their crystal ball and envision where we’d be today.

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