Butte and his colleague, postdoctoral student Sangeeta English, PhD, re-analyzed publicly available data from 49 experiments conducted using different methods in a variety of animals from humans to rats to worms. They cast a wide net: The only thing the studies had in common was that they were each designed to ferret out genes or proteins important to fat storage or body size.
"We don't make any assumptions," said Butte. "We trusted the individual investigators to come up with well-thought-out models for their experiments. What we may lose in precision - by, for example, overlooking species-specific differences - we gain in the ability to generalize. Those genes that we do identify as important are likely to be of fundamental importance."
For example, one experiment focused on an extremely rare pediatric disorder called progeria. Children with the condition appear to age rapidly and usually die in their early teens. They also happen to lose their fat cells. "Now, we don't know if this has something to do with obesity," said Butte. "But if it's at all related to fat metabolism, it may contribute something to our knowledge."
Butte and English mixed and matched pairs and small groups of experiments to identify reliable performers. Their premise was that a gene that is only weakly positive in one experiment may easily be dismissed out of hand. However, if that same gene is weakly positive in two or more experiments, the case against it becomes much stronger - particularly if those experiments used very different methods to generate their results.
The researchers' technique may also be able to pick out even previously non-positive genes for further study by allowing the background "noise," or meaningless variations found in every experiment, to cancel one another out, leaving the true positives standing tall. The effect is much like wea
|Contact: Robert Dicks|
Stanford University Medical Center