Box 2. Systems virology—'viromics'

Innovations in sequencing technologies, particularly the rapid, high-throughput pyrosequencing platforms, continue to transform large-scale biology. To illustrate this point, NCBI's GenBank contains an overwhelming 2,000 completely sequenced unique viral genomes, and 2,500 complete viral genomes of influenza A virus have been sequenced to date⁵⁸. This, along with the '$1,000 genome' goals of the Personalized Human Genome project, necessitate advances in bioinformatics and computational biology to carry out whole-genome comparisons for intrahost and interhost strains as well as for host-host variation. A stimulating commentary by Holmes⁵⁸ asks thought-provoking questions about the use of genomics data to understand evolutionary interactions between concurrently circulating pathogens in a host and their influence on disease etiology (for example, the rise of opportunistic pathogen-related infections with the HIV pandemic) and how host immunity shapes pathogen diversity and response to infection (for example, interactions among the four dengue serotypes). Furthermore, intrahost and interhost genetic variability is important in understanding cross-species transmission and emergence, with the avian H5N1 flu virus being a prime example. The fields of viral metagenomics and viral diagnostics are therefore poised for rapid expansion. Beyond the burgeoning expression profiling datasets in databases, such as NCBI's GEO, M.G.K.'s laboratory has generated over 5,000 array datasets over the past seven years using commercial and internally developed microarray platforms. Such datasets will provide clues to host determinants of infections and usher in an era of 'personalized viromics'. Along the same lines, Braga-Neto and colleagues⁵⁹ provide an illuminating discussion on the overwhelming scale and potential of immunomics, which aims to uncover host immunological responses to antigens. These developments set the stage for systems-level analyses to develop better and safer personalized treatment and preventive modalities.