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Steve Parker: An Algorithmic Awakening

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Title: Postdoc, National Human Genome Research Institute
Education: PhD, Boston University, 2009
Recommended by: Tom Tullius, Boston University

While in pursuit of his PhD in bioinformatics, Steve Parker had the good fortune to team up with several established researchers, including Boston University's Tom Tullius, who helped cement Parker's interest in comparative genomics and the structure of DNA. By the time Parker was nearly done with his PhD, he was also working with NHGRI's Elliott Margulies to develop a DNA structure-aware evolutionary constraint detection algorithm. "This method works by predicting the DNA structure at all positions in a multi-species, multiple alignment, and then measuring the similarity between species," Parker says. "We can statistically assess which regions are more similar than you would expect, and it turns out these regions tend to be enriched in non-coding functional areas of the genome, so that was pretty cool."

As a fellow at NHGRI, Parker is putting his bioinformatics skills to work as he studies evolutionary restraint across mammals and works on the institute's melanoma sequencing project, which is aimed at comprehensively characterizing all somatic variations associated with the disease. "A lot of the single nucleotide variants occur in non-coding regions and we're not sure which of these might be important," he says. "Whereas the language that describes coding regions is relatively understood, the language describing functional, non-coding regions is very poorly understood."

Currently, Parker and his colleagues are sequencing genomes using very short reads, which they then align back to a reference genome — a task for which he wishes there was an alternative method. "If there was some magical technology that had super long reads, and was high throughput enough to facilitate de novo assembly of human genomes, that would be great," he says.

Publications of note

In 2009, Parker was an author on a paper in Science that provides evidence to support the theory that the molecular shape of DNA can be used to identify evolutionary history. Parker and his colleagues presented an algorithm that measures evolutionary constraint based on the similarity of DNA topography among multiple species. Using that algorithm, the researchers found that 12 percent of bases in the human genome are constrained, which is twice the amount that had previously been detected by sequence-based algorithms.

And the Nobel goes to ...

If he were to be awarded the Nobel Prize, he'd like it be for discovering something fundamental. "How do you interpret non-coding DNA? What does all of it mean? We still don't know," Parker says. "When you get a mutation of a non-coding sequence, what does that mean in terms of cancer? These are the questions I would like to answer."

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