Perspective The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats W. Florian Fricke, David A. Rasko, Jacques Ravel* Institute for Genome Sciences (IGS), University of Maryland School of Medicine, Baltimore, Maryland, United States of America Since the publication in 1995 of the first Biodefense Funding for of programs, the genome sequences of over complete genome sequence of a free-living Genomic Research 90,000 influenza viruses were rapidly organism, the bacterium Haemophilus influ- generated and are now deposited in enzae [1], more than 1,000 genomes of Since the anthrax letter attacks of 2001, GenBank (http://www.ncbi.nlm.nih.gov/ species from all three domains of life— when letters containing anthrax spores genomes/FLU/aboutdatabase.html). Be- Bacteria, Archaea, and Eukarya—have were mailed to several news media offices cause of the availability of large sequencing been completed and a staggering 4,300 and two Democratic senators in the capacity and the large amount of informa- are in progress (not including an even United States, killing five people and tion, the response to the 2009 H1N1 larger number of viral genome projects) infecting 17 others, funding agencies in influenza pandemic was rapid and efficient (GOLD, Genomes Online Database v. the US and other countries have priori- (Box 2): Genomics information was gener- 2.0; http://www.genomesonline.org/gold. tized research projects on organisms that ated within days and validated diagnostic cgi, as of August 2009). Whole-genome might potentially challenge our security tools were approved within weeks [5,6]. A shotgun sequencing remains the standard and economy should they be used as global response was made possible through in biomedical, biotechnological, environ- biological weapons. This has resulted in tremendous research efforts enabled by mental, agricultural, and evolution- large amounts of funding dedicated to so- genomic research. ary genomics (http://genomesonline.org/ called ‘‘biodefense’’ research, totaling close gold_statistics.htm#aname). While next- to $50 billion between 2001 and 2009 [4]. Access to and Documentation generation sequencing technology is Genomics has benefited greatly from this of Sequence Data changing the field, this approach will influx of research dollars and as a result, continue to be used and lead to a representatives of most major animal, plant, Open access to genomics resources (i.e., previously unimaginable number of ge- and human pathogens have been sequenced raw sequence data and associated publi- nome sequences, providing opportunities (http://www.pathogenportal.org/). Support- cations) is an essential component of the that could not have been thought of a few ed by federal funds from the National nation preparedness to biological threats years ago. These opportunities include Institutes of Health (NIH), the National (biopreparedness), whether intentionally studying genomes in real-time to under- Institute of Allergy and Infectious Diseases delivered or not. Although some consider stand the evolution of known pathogens (NIAID), and the US Department of De- open-source genomic resources a threat to and predict the emergence of new infec- fense, research programs, such as the Micro- security [7] because they make publicly tious agents (Box 1). With the introduction bial Sequencing Centers and the Bioinfor- available information that could facilitate of next-generation sequencing platforms, matics Resource Centers (http://www3. the construction of dangerous infectious cost has decreased dramatically, resulting niaid.nih.gov/topics/pathogenGenomics/ agents, we strongly disagree with this point in genomics no longer being an indepen- PDF/genomicsinitiatives.htm), have been of view. Rather, we and others [8] believe dent discipline, but becoming a tool established that carry out genomics re- that it is an enabling tool more useful to routinely used in laboratories around the search on pathogenic organisms and have those in charge of our public health and world to address scientific questions. This spearheaded a new phase of the genomics biosecurity than to those with ill inten- global sequencing effort has been focusing revolution. Similar programs were started tions. Genomic sequence data can provide primarily on pathogenic organisms, which in Europe, such as those at the Wellcome a starting point for the development of today are still the subject of the majority of Trust Sanger Institute in the United new vaccines, drugs, and diagnostic tests genome projects [2]. Sequencing two to Kingdom, and the multinational European [9], hence improving public health capa- five strains of the same pathogen has, in effort, The Network of Excellence Euro- bilities and increasing our bioprepared- recent years, afforded us not only a better PathoGenomics (http://www.noe-epg. ness. Access to the organisms from which understanding of evolution, virulence, and uni-wuerzburg.de/epg_general.htm). As the sequences are derived should be biology in general [3], but, taken to the an example of the success of these types restricted, not their genome sequences. next level (hundreds or thousands of strains) it will enable even more accurate Citation: Fricke WF, Rasko DA, Ravel J (2009) The Role of Genomics in the Identification, Prediction, and diagnostics to support epidemiological Prevention of Biological Threats. PLoS Biol 7(10): e1000217. doi:10.1371/journal.pbio.1000217 studies, food safety improvements, public Published October 26, 2009 health protection, and forensics investiga- Copyright: ß 2009 Fricke et al. This is an open-access article distributed under the terms of the Creative tions, among others. Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Competing Interests: The authors have declared that no competing interests exist. The Perspective section provides experts with a forum to comment on topical or controversial issues * E-mail: [email protected] of broad interest. This article is part of the ‘‘Genomics of Emerging Infectious Disease’’ PLoS Journal collection (http:// ploscollections.org/emerginginfectiousdisease/). PLoS Biology | www.plosbiology.org 1 October 2009 | Volume 7 | Issue 10 | e1000217 Author Summary vocabulary should be developed to de- scribe these isolates and the genes they contain. Such efforts have already started, In all likelihood, it is only a matter of time before our public health system will for example through the open-access face a major biological threat, whether intentionally dispersed or originating from journal Standards in Genome Sciences a known or newly emerging infectious disease. It is necessary not only to increase (SIGS) (http://standardsingenomics.org/ our reactive ‘‘biodefense,’’ but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public index.php/sigen), but the dedicated re- health communities fully embrace the genomic revolution, and that novel sources are not adequate and highlight the bioinformatic and computing tools necessary to make great strides in our lack of understanding of the importance of understanding of these novel and emerging threats be developed. Genomics has metadata in genomics. Initiatives such as graduated from a specialized field of science to a research tool that soon will be those of the Genomics Standards Consor- routine in research laboratories and clinical settings. Because the technology is tium have made great strides [11,12], but becoming more affordable, genomics can and should be used proactively to still need widespread implementation build our preparedness and responsiveness to biological threats. All pieces, from the ever-expanding genomic com- including major continued funding, advances in next-generation sequencing munity. Open access to the genomic DNA technologies, bioinformatics infrastructures, and open access to data and that has been sequenced or the culture metadata, are being set in place for genomics to play a central role in our public from which the DNA was extracted and to health system. the associated metadata is key to success- ful genome sequencing projects, whether on single or several hundred genomes or Now that genomics technologies are species. Access to relevant, well-curated metagenomes. Well-documented genome broadly available, there is the potential culture collections [10] and DNA prepa- sequence data will form a key growing for commercial interests to hamper the rations suitable for sequencing may be- resource for biodefense and other re- release of genomic data in the public come a bottleneck in the future when search fields. domain. Thus it is important that federally sequencing resources are no longer limit- funded large-scale genome sequencing ing. More importantly, the impact of large Emerging New Bioinformatics efforts have enforceable rapid release genomic sequence datasets from clinical Resources policies. This accessibility could afford isolates will be limited without key clinical further opportunities to capitalize on metadata that characterize these isolates, As we enter a new era of modern investments in genome sequencing by such as patients’ medical information, genomics, the ever-expanding sequence providing the necessary resources to bio- date of isolation, and the number of datasets are becoming more challenging to preparedness. culture passages in the laboratory. Open analyze. Future analysts