Genomics of Emerging Infectious Disease: A PLoS Collection

Today, the Public Library of Science publishes a collection of essays, perspectives, and reviews about how genomics, with all its associated tools and techniques, can provide insights into our understanding of emerging infectious disease (http://ploscollections. org/emerginginfectiousdisease/) [1–13]. This collection, focused on human disease, is particularly timely as pandemic H1N1 2009 influenza (commonly referred to as swine flu) spreads around the globe, and government officials, the public, journalists, bloggers, and tweeters strive to find out more. People want to know if this flu poses more of a threat than other seasonal flu strains, how fast it’s spreading (and where), and what can be done to contain it. As this collection illustrates, the increasing speed at which complete genome sequences and other genome-scale data can be generated for individual isolates and strains of a pathogen provides tremendous opportunities to identify the molecular changes in these disease agents that will enable us to track their spread and evolution through time (e.g., [3,7,8]) and generate the vaccines and drugs necessary to combat them (e.g., [5–7]). The collection also shines a spotlight on specific pathogens, some familiar and widespread, such as the influenza A virus (e.g., [9]); some ‘‘reemerging,’’ such as the Mycobacterium tuberculosis complex that causes tuberculosis [10]; and some identified only recently, as with the bacterium Helicobacter pylori (which causes peptic ulcers and gastric cancer [11]). There is no simple definition of an emerging disease, but it can be loosely described as a disease that is novel in some way—for example, one that displays a change in geographic location, genetics, or function. Emerging infectious diseases are caused by a wide range of organisms, but they are perhaps best typified by zoonotic viral diseases that cross from animal to human hosts and can have a devastating impact on human health, causing a high disease burden and mortality [8]. These zoonotic diseases include monkeypox, Hendra virus, Nipah virus, and severe acute respiratory syndrome coronavirus (SARS-CoV), in addition to influenza A and the lentiviruses that cause AIDS. The apparently increased transmission of pathogens from animals to humans over the recent decades has been attributed to the unintended consequences of globalization as well as environmental factors and changes in agricultural practices [8]. Generally, the burden of these diseases is most strongly felt by those in developing countries. Brindley et al. [12] point to the debilitating effects of the most common human infectious agent in such areas—helminths (parasitic worms)—and the role that genomics plays in advancing our understanding of molecular and medical helminthology. Compounding the problem of emerging infectious diseases in developing countries is the reality that researchers in developing countries have often been unable to participate fully in genomics research, because of their technological isolation and limited resources. As Harris et al. emphasize [13], ‘‘collaborations— starting with capacity building in genomics research—need to be fostered so that countries that are currently excluded from the genomics revolution find an entry point for participation.’’ This collection is a collaborative effort that combines financial support from Google.org (which has also sponsored research on emerging infectious disease through its Predict and Prevent initiative [14]) with PLoS’s editorial independence and rigor. Gupta et al. [1] provide Google.org’s perspective and vision for how systematic application of genomics, proteomics, and bioinformatics to infectious diseases could predict and prevent the next pandemic. To realize this vision, they urge the community to unite under an ‘‘Infectious Disease Genomics Project,’’ analogous to the Human Genome Project. This is, as the authors admit, a potentially ‘‘grandiose’’ and difficult proposition. Some researchers might justifiably argue that much is already being achieved—as demonstrated by this collection—and that the vision is naı̈ve. However, as every article in the collection also points out, tremendous challenges remain if the potential of genomics in this field is to be realized. One problem is that, despite the fact that sequencing is now the method of choice for characterizing new disease agents, and new substantially faster and cheaper sequencing methods are continually being produced, we still lack the range of computational tools necessary to analyze these sequences in sufficient detail [4]. It is possible to sequence the entire assemblage of viruses in a particular tissue type or host species [3] and to obtain complete or nearly complete genome sequences for large samples of bacteria [7]. Yet we remain in the early, albeit essential, stages of pathogen discovery (Box 1). These sequences can be interpreted fully only when integrated with relevant environmental, epidemiological, and clinical data (e.g., [3,4,8]). And, despite the increased sequencing, really comprehensive genome data are still only available for a few key pathogens, which further limits our understanding. For example, a full quantitative understanding of the processes that shape the epidemiology and evolution—the phylodynamics—of RNA viruses is currently possible only for HIV and influenza A virus [3]. In this collection, you will find not only the views of leading researchers from several different disciplines, and a provocative vision from a funding agency, but also the contributions of six different PLoS journals (PLoS Biology, PLoS Medicine, PLoS Computational Biology, PLoS Genetics, PLoS Neglected Tropical Diseases, and PLoS Pathogens). The PLoS open-access model of publishing makes possible such a large multidisciplinary cross-journal collection, in which all articles are simultaneously available online