Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing

Ladner, Jason T.; Beitzel, Brett; Chain, Patrick S. G.; Davenport, Matthew G.; Donaldson, Eric; Frieman, Matthew; Kugelman, Jeffrey; Kuhn, Jens H.; O’Rear, Jules; Sabeti, Pardis C.; Wentworth, David E.; Wiley, Michael R.; Yu, Guo-Yun; Sozhamannan, Shanmuga; Bradburne, Christopher; Palacios, Gustavo

Molecular epidemiology. One of the most common and important applications for viral genomes is in the study of viral epidemiology, which encompasses our understanding of the patterns, causes, and effects of disease. Early studies of molecular epidemiology targeted small pieces of viral genomes; however, this type of analysis is likely to miss important changes elsewhere in the genome. Therefore, there has been a strong focus in recent years toward the sequencing of "full" viral genomes. Institutes such as the Broad Institute and the J. Craig Venter Institute (JCVI) have been instrumental in breaking ground in the collection of large numbers of good-quality viral sequences. Their newly identified genomes typically fall within our CC category. This is likely to remain the gold standard for studies involving a large number of genome sequences, especially when some samples come from lowtiter clinical samples, often necessitating amplicon-based sequencing methods. CC genomes allow for interrogation of changes throughout the coding portion of the viral genome and often include partial noncoding regions. In the absence of highthroughput RACE alternatives, the time and resources required to complete hundreds or thousands of genomes are likely to continue to outweigh the potential information gained from completing the terminal sequences.