By David Kattenburg
Debron, Luke and Paula huddle around a laptop in a McGill University cafeteria, deeply absorbed in an online game. Listen to them here:
No dreadful monsters, zombies or bloody explosions here. No violence or aggression of any sort. Phylo is much more serious than that. The mission of these three Montreal students is to solve a DNA puzzle; to pinpoint mutations in the human genetic code that cause cancer and other human disorders.
DNA sequence alignment is what Phylo — developed by McGill researchers Jerome Waldispuhl and Mathieu Blanchette — is all about.
- By aligning homologous sequences of DNA code from humans and a variety of other species, the gamer isolates mutations in the human version that could potentially be linked to genetic malfunction.
Accumulated mutations in genes that have been around for many millions of millenia — as far back as the birth of the fungi — are typically the sorts of segments that trigger diseases in humans or allow them to advance. Spotting candidate mutations in databased sequences, establishing their precise “architecture,” is therefore an obvious thing to do.
But the “heuristics” (mathematical approach to an optimal solution) are complex, says McGill bioinformatician Guillaume Bourque, another contributor to Phylo’s development.
Supercomputers do a great job parsing raw DNA alignments for good fits, from which human differences (mutations) can be deduced. These could involve simple transpositions of one of the four DNA “letters” (A,G, C, T), and more complex shifts involving inserted or deleted chunks of code (“indels”) that throw versions completely out of alignment with each other.
When it comes to fine tuning, though, there’s nothing like the human eye. Not surprising, really. Humans can distinguish facial and vocal features that fly right over a computer’s head. The human eye is nothing short of brilliant. This is where a game like Phylo comes in.
Discerning eyes focused, Phylo players scrutinize computer-derived alignments that have been turned into puzzles, consisting of a set of DNA nucleotide sequences represented as colored blocks, each a chunk of DNA code that humans and other animal species have in common.
Each row in a Phylo game represents a different version of the code somewhere on the phylogenetic tree — from a mouse, rat, snake, or insect. Each has its own unique gaps, insertions and deletions that throw it out of alignment with those above and below.
Mouse in hand or finger on the touchpad, a Phylo player slides multicolored blocks this way and that, across each row, aligning them as best as they can, on behalf of the researcher who submitted the gene, and science-at-large.
In exchange for their time and visual intuition, Phylo players like Debron, Luke and Paula will be cited in future scientific papers simply as “Phylo users.” Anonymous gamers around the world have solved almost a quarter million Phylo puzzles, involving a variety of genetically linked disorders, demonstrating once again the power of crowd-sourcing in the advancement of science and technology.
Listen to the audio story. Click on the audio button on top. Wanna play Phylo? Go here.