Stanford/Packard researchers find disease genes hidden in discarded data

Oct 24, 2007

Previously hidden obesity-related genes have been uncovered from old experiments by researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital. The finding suggests that useful information about many medical disorders may be languishing in mountains of discarded data.

"We've devised a fairly simple way to convert large amounts of existing raw data into candidate disease genes for further genetic study," said Atul Butte, MD, PhD, a pediatrician at Packard Children's and director of the hospital's Center for Pediatric Bioinformatics. "When we put the information together, we were not only able to pinpoint those that have already been identified, but we also came up with some very interesting new predictions."

The investigators teased out the existence of more than a dozen new obesity-related genes by comparing the results of 49 independent experiments conducted by other researchers - none of which had yielded similar results on their own.

Butte, who is also an assistant professor of medicine and of pediatrics at the medical school, plans to investigate the biological roles of the new genes soon. The research appears in the Oct. 5 advance access section of the journal Bioinformatics.

Identifying novel genetic culprits for complicated diseases like obesity, diabetes and autism is tricky. Unlike cystic fibrosis, which is caused by a mutation in just one gene, these conditions are often the result of a "perfect storm" of interacting genes and environmental factors. This complexity leaves researchers with limited time to pursue only their most promising results, leaving other candidates behind.

Managing the unused data can be extremely challenging. Microarray or gene-chip experiments, for example, generate tens of thousands of pieces of information. Because most scientific journals require the authors to submit all of their data to publicly available international databases, Butte estimates that the volume of such data is doubling or tripling each year.

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 wearing a pair of noise-cancelling headphones on an airplane in order to hear your favorite symphony.

The researchers knew they were on the right track when they pinpointed about 66 percent of nearly 300 previously identified obesity-related genes. In contrast, none of the individual experiments identified more than 30 percent of the same panel, and the average experiment identified only 2 percent.

Further analysis identified 16 genes that were positive in six or more experiments, and three that were positive in eight experiments. Of those three, one was a known obesity gene. The other two have no known ties to obesity, yet. "Now we can take these two candidates straight to the geneticists and the lab to begin figuring out what they do," said Butte.

The comparison approach should be applicable to many other disorders. "The data are out there," said Butte, who has pioneered ways to categorize and index the vast quantities of biomedical information in preparation for further study. "We need to translate it and make it useful for other researchers and disorders."

Source: Stanford University Medical Center

Explore further: Genetic testing in kids is fraught with complications

Related Stories

Fuel and chemicals from steel plant exhaust gases

1 hour ago

Carbon monoxide-rich exhaust gases from steel plants are only being reclaimed to a minor extent as power or heat. Fraunhofer researchers have developed a new recycling process for this materially unused carbon resource: They ...

Researchers discover how petunias know when to smell good

Jun 29, 2015

Good timing is a matter of skill. You would certainly dress up for an afternoon business meeting, but not an evening session of binge-watching Netflix. If you were just a few hours off in your wardrobe timing, ...

Can pollution help trees fight infection?

Jun 29, 2015

Trees that can tolerate soil pollution are also better at defending themselves against pests and pathogens. "It looks like the very act of tolerating chemical pollution may give trees an advantage from biological ...

Recommended for you

Genetic testing in kids is fraught with complications

Jul 02, 2015

A woman coping with the burden of familial breast cancer can't help but wonder if her young daughter will suffer the same fate. Has she inherited the same disease-causing mutation? Is it best to be prepared ...

Cause of acute liver failure in young children discovered

Jul 02, 2015

Acute liver failure is a rare yet life-threatening disease for young children. It often occurs extremely rapidly, for example, when a child has a fever. Yet in around 50 percent of cases it is unclear as to why this happens. ...

Genome sequencing illuminates rare Aicardi syndrome

Jul 02, 2015

As my inbox fills with ever more updates on the number of human genomes sequenced and the plummeting time and cost of next next next generation sequencing, I find myself hitting delete more and more often. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.