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Epidemics and pandemics have occurred since the beginning of time, resulting in millions of deaths. Many such disease outbreaks are caused by viruses. Some viruses, particularly RNA viruses, are characterized by their high genetic variability, and this can affect certain phenotypic features: tropism, antigenicity, and susceptibility to antiviral drugs, vaccines, and the host immune response. The best strategy to face the emergence of new infectious genomes is prompt identification. However, currently available diagnostic tests are often limited for detecting new agents. High-throughput next-generation sequencing technologies based on metagenomics may be the solution to detect new infectious genomes and properly diagnose certain diseases. Metagenomic techniques enable the identification and characterization of disease-causing agents, but they require a large amount of genetic material and involve complex bioinformatic analyses. A wide variety of analytical tools can be used in the quality control and pre-processing of metagenomic data, filtering of untargeted sequences, assembly and quality control of reads, and taxonomic profiling of sequences to identify new viruses and ones that have been sequenced and uploaded to dedicated databases. Although there have been huge advances in the field of metagenomics, there is still a lack of consensus about which of the various approaches should be used for specific data analysis tasks. In this review, we provide some background on the study of viral infections, describe the contribution of metagenomics to this field, and place special emphasis on the bioinformatic tools (with their capabilities and limitations) available for use in metagenomic analyses of viral pathogens.

Virus pandemics have happened, are happening and will happen again. In recent decades, the rate of zoonotic viral spillover into humans has accelerated, mirroring the expansion of our global footprint and travel network, including the expansion of viral vectors and the destruction of natural spaces, bringing humans closer to wild animals. Once viral cross-species transmission to humans occurs, transmission cannot be stopped by cement walls but by developing barriers based on knowledge that can prevent or reduce the effects of any pandemic. Controlling a local transmission affecting few individuals is more efficient that confronting a community outbreak in which infections cannot be traced. Genetic detection, identification, and characterization of infectious agents using next-generation sequencing (NGS) has been proven to be a powerful tool allowing for the development of fast PCR-based molecular assays, the rapid development of vaccines based on mRNA and DNA, the identification of outbreaks, transmission dynamics and spill-over events, the detection of new variants and treatment of vaccine resistance mutations, the development of direct-acting antiviral drugs, the discovery of relevant minority variants to improve knowledge of the viral life cycle, strengths and weaknesses, the potential for becoming dominant to take appropriate preventive measures, and the discovery of new routes of viral transmission.