CSI: Bioinformatics
Forensic Bioinformatician Aims To
Solve Mysteries of Biomarker Studies
Liz Savage
Originally published on pages 983 and 987 of the Journal of the National Cancer Institute, Oxford University Press, July 2008.
K
eith Baggerly, Ph.D., is not a Baggerly’s most publicized case involved an article published in
detective in the traditional 2002 in The Lancet. The authors had presented a new blood test
sense—he doesn’t solve mys- that they said could determine with nearly 100% accuracy wheth-
teries or fight crime. But his job does er a woman had ovarian cancer by analyzing a pattern of protein
involve digging through data to get to expression. The prospect of a noninvasive ovarian cancer screening
the truth. Instead of reconstructing test elicited much excitement because there is currently no way to
crime scenes, Baggerly spends part of detect ovarian cancer in its early stages. Nonetheless, there was con-
his time reconstructing scientific anal- cern over the reproducibility of the results, and the case encouraged
yses, a new field that many call foren- debate about the validation of proteomic studies more generally.
sic bioinformatics. M. D. Anderson investigators, like many others, wanted to try
In recent years, the new “-omics” out the new test for themselves, so they enlisted Baggerly and his
sciences, including proteomics and colleagues to show them how to reproduce the results. But they
Baggerly
genomics, have excited researchers couldn’t, and ultimately the team determined that the apparent
with their potential for revealing the difference between cancerous and normal tissues had nothing to
secrets of cancer. Yet they have also brought a new level of complex- do with the biology of the samples. Rather, they concluded, it
ity to the cancer field, and with it concerns about validation and was due to problems in the trial design: All the cancerous speci-
reproducibility. And that’s where Baggerly comes in. mens were run on one day and all the controls on another, rather
“
It’s important for people to realize that incorrect molecular profiling
results [for example] can be as dangerous as bad treatments. It’s so
critical that someone really take a close look at these things
”
.
To correctly apply the new genomic findings to the patients at than in random order. “There was a screw-up in experimental
hand, the analyses that produced these findings must be understood design, and that was one of the things that was driving the final
in detail. Thus, for the last few years Baggerly and his colleagues at results,” Baggerly said.
the University of Texas M. D. Anderson Cancer Center in Houston Such examples have highlighted the danger of acting on results
have tackled the difficult job of reproducing some complex analyses. that have not been validated. “A lot of these findings that he’s
Using the raw data and results from a study, they try to reconstruct reported on … are things that people are ready to put into clinical
how the original researchers conducted their analysis and produced trials if they believe the results,” said Lisa McShane, Ph.D., a statis-
the published findings. The task is not always straightforward. tician at the National Cancer Institute. “I think that it’s important
Often, there is not enough information in the original report to for people to realize that incorrect molecular profiling results [for
figure out how the researchers got their results, and sometimes, even example] can be as dangerous as bad treatments. It’s so critical that
after intermediate results are obtained, it is still unclear how the someone really take a close look at these things.”
researchers put them all together. Although Baggerly’s colleagues are quick to praise him, they
“We’re trying to piece together whether [the results] make sense, also point out that, in an ideal world, he wouldn’t be a forensic
and if they don’t make sense, [we ask] how they might nonetheless statistician—no one would. His work, though important, points
have come about. That’s something that we’ve had a good deal of to a greater problem in how science is conducted and presented.
trouble figuring out in some instances,” Baggerly said. “And every “I think Keith is doing a wonderful and needed job because he’s
once in a while, we get a situation where we look at the data [after uncovering potential problems that need to be anticipated and
reproduction] and say, ‘Actually, we’re not convinced that this avoided,” said David Ransohoff, M.D., professor of medicine at
does work.’ ” the University of North Carolina at Chapel Hill. “But the fact that
OCTOBER 2008 AMSTAT NEWS 19
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