RT Journal Article
SR Electronic
T1 High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 005702
DO 10.1101/005702
A1 Nicholas C. Wu
A1 Arthur P. Young
A1 Laith Q. Al-Mawsawi
A1 Anders C. Olson
A1 Jun Feng
A1 Hangfei Qi
A1 Shu-Hwa Chen
A1 I-Hsuan Lu
A1 Chung-Yen Lin
A1 Robert G. Chin
A1 Harding H. Luan
A1 Nguyen Nguyen
A1 Stanley F. Nelson
A1 Xinmin Li
A1 Ting-Ting Wu
A1 Ren Sun
YR 2014
UL http://biorxiv.org/content/early/2014/05/31/005702.abstract
AB A novel genome-wide genetics platform is presented in this study, which permits functional interrogation of all point mutations across a viral genome in parallel. Here we generated the first fitness profile of individual point mutations across the influenza virus genome. Critical residues on the viral genome were systematically identified, which provided a collection of subdomain data informative for structure-function studies and for effective rational drug and vaccine design. Our data was consistent with known, well-characterized structural features. In addition, we have achieved a validation rate of 68% for severely attenuated mutations and 94% for neutral mutations. The approach described in this study is applicable to other viral or microbial genomes where a means of genetic manipulation is available.