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Shirleen Soh works in the Bloom Lab at the Fred Hutchinson Cancer Research Center. (Robert Hood / Fred Hutch Photo)

As migratory birds make their way north this spring, few people will look to the sky and think, “God help us. Here they come.”

It has been 101 years since the onset of the Spanish Flu, a virus that may have derived from bird flu that killed 3 to 5 percent of the world’s population. Ever since then, the threat that an equally fatal flu might strike has loomed large.

Now, scientists at the Fred Hutchinson Research Center are digging deep into how the virus jumps from birds to people. The researchers have mapped all the ways that a critical protein in influenza can mutate to make the virus more likely to cross species.

The new map could help scientists predict which flu strains present the greatest threats and act faster to target those viruses with a vaccine.

Scientists don’t currently know “how well a particular virus is going to do in a human host,” Dr. Shirleen Soh, a postdoctoral fellow at Fred Hutch and lead author on the paper, said in an announcement.

Soh took a protein in bird flu called PB2 and mutated it, later testing whether the changes caused the flu to grow stronger in human cells. Armed with a list of the most problematic mutations, Soh then realized that only a few of them had ever been recorded in cross-species influenza jumps.

Soh, who is based in the lab of computational biologist Dr. Jesse Bloom, worked with postdoctoral fellow Dr. Louise Moncla to compare the mutations to those seen in different types of H7N9, a flu strain that first infected people in China six years ago.

“We were able to take Shirleen’s map and see that many H7N9s that jumped into humans did have evidence of adaptive mutations, including some mutations that we hadn’t known about before Shirleen’s mapping experiment,” Bloom said.

The findings could help future scientists figure out which mutations are most likely to move across species. The team hopes to make the data accessible to others by integrating it into NextStrain, a platform that tracks how the flu evolves.

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