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Biostatistician works to ‘translate’ the human genome

David Conti, assistant professor of preventive medicine at the Keck School of Medicine, is a biomedical jack-of-all-trades.

Conti, who joined the Keck School and the Zilkha Neurogenetic Institute in December 2002, is a biostatistician who creates statistical methods and tools for use in genetic epidemiology.

“Basically, I use statistical methods to determine how genetic variation leads to disease outcomes or traits,” Conti explained.

These are techniques that can apply to almost any disease—or, for that matter, to normal biology or behaviors. And Conti has made the most of his field’s lack of boundaries, working on topics that range from prostate cancer to smoking behaviors.

“This is a great time to be doing this kind of work,” he said. “The Human Genome Project started us off, but there’s so much to be done. We can read the letters of the genome now, but we don’t know what they say. My job is to help do some of the translation.”

He does this by helping researchers design experiments and create models that will allow them to tease out variations in genes related to a specific biomedical topic, and to determine which of those variations have an effect on the disease or the behavior in question.

To that end, Conti is currently working with researchers at the Keck School’s Transdisciplinary Tobacco Use Research Center (TTURC) to find statistical methods by which the TTURC scientists can assess various health and behavioral changes in people who smoke. “For instance,” Conti said, “they’re looking at behavioral outcomes such as aggression and depression, and how they relate to smoking—and then at how genetic variations relate to all of this.”

Conti is also working with the basic scientists at the Zilkha to help them narrow down the field in their individual searches for genetic variations linked to neurodegenerative and neuropsychological diseases.

“The main question I’m trying to help people find answers to is how do we analyze genes within a pathway that’s within a disease?” Conti explained. “What’s the best way to design a study to find genes and determine their impact on disease? And how can we incorporate our knowledge of biology into our statistical analyses?”

In addition, Conti is currently considering the best methods by which to define which of the numerous variations—also known as polymorphisms—that are present in essentially every known gene are important and worthy of further investigation, and which are completely silent or without a measurable impact.

Conti came to USC from Case Western Reserve University in Cleveland. In March 2004, some of his work at Case Western was showcased in the journal Science, to show how chromosome-substitution strains of mice can help geneticists pick out individual influences on complex developmental, physiological and behavioral traits.

“There are things you can do with mice that you can’t do with humans, obviously, such as selective mating,” Conti explained. “It took seven years of work to get a strain of mice that were similar on all their chromosomes except for one, which was the basis of the Science paper. But now that we have them, there are endless possibilities for what we can study.”

Conti added: “This is the kind of work that can cross disciplines and disease boundaries. That’s why I find it so compelling.”

Biostatistician works to ‘translate’ the human genome

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