Zika genomics urgently need standardized and curated reference sequences

Abstract

Emerging viral epidemics pose a threat to public health globally. The recent spread of the Zika virus (ZIKV) across the Pacific region and the Americas is particularly disturbing, given its association with severe birth malformations. On February 1, 2016, the World Health Organization (WHO) declared ZIKV a Public Health Emergency of International Concern, which prompted a global response to improve our understanding of ZIKV epidemiology and disease manifestations. Intensified ZIKV surveillance and real-time sharing of novel scientific evidence coincided with a scaling up of ZIKV whole genome sequencing for public health purposes and diagnostics [1,2]. As a result, most human ZIKV genomes available to date originate from the ongoing outbreak. While this proliferation of genomic data offers new opportunities for comparative and evolutionary genomics of ZIKV, we demonstrate that the rapid advance in ZIKV genomics has resulted in inconsistencies that complicate the interpretation, reproducibility, and comparison of findings from and across studies, particularly due to the lack of consensus on a standardized and representative reference genome annotation. ZIKV reference genomes do not match virus strains sampled from the global epidemic or are not adequately annotated at the protein level, and current heterogeneity in study methodology ultimately limits the full potential of ZIKV genomics. In this letter, we address the need for curation and standardized annotation of ZIKV reference genomes in order to guide researchers and clinicians in genomic analyses and the translation of research findings.