Open sourcing an outbreak investigation

The Germany-based Escherichia coli outbreak that killed at least 50 people and hospitalized thousands  in May and June of 2011 has been declared officially over. Researchers credit advances in DNA-sequencing technologies and the ability to freely share data and collaborate with groups of researchers around the globe for the rapid analysis of the genome of the offending e. coli variant.

In two studies published online in the New England Journal of Medicine on July 27, scientists say that the culprit in this outbreak is unusually virulent and contains a gene that produces the Shiga toxin. This situation is only made worse by certain antibiotics that cause more toxin to be produced. Both studies identify this E coli strain as largely enteroaggregative, uniquely combined with the enterohemorrhagic E coli subtype, and associated with symptoms including severe diarrhea and hemolytic-uremic syndrome. The source of the outbreak was identified by the European Food Safety Authority as bean sprouts from fenugreek seeds (Trigonella foenum-graecum) imported from Egypt.

Both publishing research groups working on this outbreak highlight the speed with which they obtained their results. This has been the fastest analysis of an outbreak-associated bacterial pathogen we know of, and now many believe this open source method of sharing data can (and should) play a significant role in public health emergencies.

BGI and its collaborators at the University Medical Centre Hamburg-Eppendorf, Beijing Institute of Microbiology and Epidemiology, and China's Centers for Disease Control (CDC) (among others) sequenced the genome of E. coli isolate within three days, using the Ion Torrent Personal Genome Machine.

Dr. Junjie Qin, Principal Investigator at BGI and one of the co-leading authors of the collaboration's study said, “In order to reveal the mechanisms of infection and control the spread of this epidemic as soon as possible, we together with our partners launched a rapid open-source genomics program for immediate data release and to provide more available genome data to the global researchers.”

Professor Ruifu Yang, research fellow at the Beijing Institute of Microbiology and Epidemiology, reiterates those sentiments. “This study not only lays an important foundation for tracing down the evolutionary origins and pathogenic potential of this epidemic's strain but also opens a way to countermeasure infectious diseases by a new model of international collaboration.”

The other study was published by Scientists at the University of Maryland Institute for Genome Sciences, in collaboration with scientists from Pacific Biosciences of California Inc., Denmark’s Statens Serum Institute, Harvard, and the University of Virginia. Their work on this E. coli outbreak cost $500,000 and began producing data within days.

David A. Rasko, assistant professor at the University of Maryland School of Medicine and research scientist at the Institute for Genome Sciences, led the investigation that helped U.S. food investigators make sense of the E. coli outbreak in spinach in 2006 and assisted the FBI in tracing the anthrax attacks in 2001. Rasko said that work had cost millions and taken months. “Usually, science takes place in relative isolation,” Dr. Rasko said. “This is the first time we've seen true 'open source' analysis of a microbial genome... This paper and the research it describes represent the new paradigm of outbreak investigations.”

Eric Schadt, Ph.D. and chief scientific officer of Pacific Biosciences, as well as co-author of the paper, explains, “We have reached a new era in which communities of researchers can rapidly share large-scale datasets and analyses vital for public health. Sequencing genomes in hours, as opposed to days or weeks, with unprecedented read lengths, is the emerging hallmark of third-generation DNA sequencing.”