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William Bush: Layers of Complexity Between Bases and Disease

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Title: Assistant professor, Vanderbilt University
Education: PhD, Vanderbilt University, 2009
Recommended by: Jonathan Haines, Marylyn Ritchie, both at Vanderbilt University

William Bush is interested in what goes on in the middle. Recently, researchers have been focused on using genome-wide association studies to home in on single base pair changes implicated in complex phenotypes or diseases. "Making a relationship between a single base pair change in the genome and something as complex ... as multiple sclerosis is an enormous leap," he says, though he notes that the flood of results shows that's been a valid approach.

"There are layers of complexity between those two extremes," Bush adds. "I'm very interested in understanding the intermediate, both on the phenotypic spectrum ... [and] also intermediate structures and mechanisms on the more genetic end." In particular, Bush is interested in how genetic variation influences different forms of cancer and multiple sclerosis as well as the mechanisms through which these influences work, and he is using algorithms to study that.

In his computational lab, Bush is combing through publicly available data to ask his research questions. His general approach is then to verify and validate those findings in focused studies. "There is an enormous wealth of gene expression data and genotype data and even resources that [contain] structure phenotype classes and a lot of times, if you know how to link data together, you can get to the point where you can ask really interesting questions about how all these things interrelate," he says.

The work is not without its frustrations, though. Bush says that it is sometimes difficult to find the resources or data set that he needs to make headway in his work. Getting the word out to his fellow researchers about all the resources available can be difficult. To that end, Bush says he'll soon be releasing a tool that presents the information in a more user-friendly context.

Looking ahead

The field is on the cusp of a transition, Bush says. Within the next five years he sees whole-genome sequencing supplanting GWAS. The first step, which is already beginning to occur, is using exome sequencing, though Bush says whole genome sequencing will quickly follow as it becomes more cost effective. "I see enormous opportunity for researchers ... to try to make sense of the enormous wealth of data that's coming out," he says. "We're transitioning to a point where we're becoming more data scientists that really have to get ahold of multiple types of data to really understand what that data means in the context of a given disease phenotype."

Papers of note

As part of his thesis work, Bush worked on a tool to integrate various data resources for GWAS analysis. The result, Biofilter, was published in the Proceedings of the Pacific Symposium on Biocomputing conference in 2009. Bush notes that his advisor, Marylyn Ritchie, is continuing to develop it as a software and analysis tool. "I am very proud that we were among the first groups to develop tools that facilitate that type of analysis," he says.

And the Nobel goes to ...

"This is horribly generic, but it would be very fulfilling to know that I've made a contribution to human health," Bush says.

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