Medical Device Daily Staff Report

Pathogens evolve over time, often faster than humans are able to react to quell disease spread. In the war of humans vs. infectious diseases, a team of astute scientists has nudged humankind ahead of these stealthy microorganisms by inventing what could be described as a weather map for pathogen tracking. Supramap, a web-based application that maps the evolution of genetic mutations of infectious diseases, could very well be the weapon that will help us to outwit a multitude of dangerous diseases.

"The Centers for Disease Control and Prevention (Atlanta) is more concerned with specific, medically identifiable strains and how they are distributed, as opposed to looking at how their evolution proceeded. We're looking at biogeography," Ward Wheeler, PhD, curator in the Division of Invertebrate Zoology at the American Museum of Natural History (New York), told Medical Device Daily. Biogeography uses geographic information systems (GIS) to help understand the distribution of organisms, ultimately to predict future trends, such as the spread of a disease as it mutates and evolves.

Wheeler, along with Daniel Janies, an associate professor of biomedical information at Ohio State University (OSU; Columbus), has co-authored a paper in Cladistics with an international team of scientists which explains how the program they developed, called Supramap, can be used to study and combat infectious disease outbreaks.

Operating on parallel programming on high-performance computing systems at OSU and the Ohio Supercomputer Center, Supramap advances the use of genetic information in studying infectious outbreaks a step further. This application integrates genetic sequences of pathogens with geographic information so that researchers can track the spread of a disease among different hosts and follow the emergence of key mutations across time and space.

With Supramap, users can submit raw genetic sequences and obtain a phylogenetic tree of strains of pathogens. The resulting tree is then projected onto the globe by Supramap and can be viewed with a program such as Google Earth. Each branch in the evolutionary tree is geo-located and time-stamped. Pop-up windows and color of branches show how pathogen strains mutate over space and time and infect new hosts. For example, you can click on a pop-up window to see mutations that distinguish one strain of the virus from another.

The tool has allowed researchers to better understand whether the mutations associated with hosts or geographic regions appeared by chance or whether they were true adaptations of the virus as it spread.

"The idea is to link biogenetic information," Wheeler said. "Evolutionary trees are linked with GIS to track the evolution of viruses in both space and time. If it's a virus like influenza, then it tells us how viruses are evolving and dispersing."

Supramap sounds complex, but the team said the application is packaged so that one doesn't need a PhD in evolutionary biology or computer science to understand the trajectory and transmission of a disease.

"This tool also has a lot of predictive power," Wheeler said. "If the movement of a pathogen is related to bird flyways, and those routes are shifting because of something like climate change, we can predict where the disease might logically emerge next."

He explained that these kinds of data may help public health officials to know whether or not a shipment of Tamiflu to a certain part of the world is appropriate or if an outbreak appears to be a strain that's likely resistant to the antiviral drug. Smarter and faster public health decisions can reduce sickness, death and costs in one swoop.

The study of the relationships and evolutionary trajectory of organisms, called phylogenetics, is crucial to make sense of related phenotypic and genomic data. All of these tools feed into the predictive power of Supramap.

For example, the collection of genomic sequences of the coronavirus that causes Severe Acute Respiratory syndrome (SARS) and various strains of the influenza A virus have become an vital part of fighting outbreaks. The initial jump of a pathogen into humans has become increasingly important to understand because of growing human-animal contact and increasing global travel. Researchers now know, for example, that SARS has a deep evolutionary origin in bats. H1N1, we know, comes from pigs.

Wheeler's team tested Supramap's abilities by entering genetic and geographic data on recent isolates of avian influenza. The diversity of viral strains from birds and mammals in China, Russia, the Middle East, Africa, and Europe are represented as they spread westward over four years. That evolutionary tree shows that host shifts are highly correlated with a specific mutation that allows avian viruses to adapt to mammalian hosts.

"Biogeography and phylogeny, or the study of evolutionary and geographic relationships among organisms, are the core areas of research in the museum," said Wheeler. "Our expertise is now being applied to a new, practical set of research questions, the spread of disease and human health."

Other institutions involved in the development of Supramap include the Indian Institute of Science Education and Research (Pune, India), Universidade Federal de Minas Gerais (Belo Horizonte, Brazil) and City University of New York. It was funded by the U.S. Army Research Laboratory and Office (Adelphi, Maryland) and the Defense Advanced Research Projects Agency (Arlington, Virginia), Ohio State University, fund of the Tides Foundation (San Francisco), and the American Museum of Natural History.

Supramap is an open source software, free to use.

"We wanted to make this tool available for all to use," Wheeler said. "We also wanted to make it easy for people to use as part of making public health decisions."

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Lynn Yoffee; 770-361-4789