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High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution

Nicholas C. Wu, Arthur P. Young, Laith Q. Al-Mawsawi, Anders C. Olson, Jun Feng, Hangfei Qi, Shu-Hwa Chen, I-Hsuan Lu, Chung-Yen Lin, Robert G. Chin, Harding H. Luan, Nguyen Nguyen, Stanley F. Nelson, Xinmin Li, Ting-Ting Wu, Ren Sun
doi: https://doi.org/10.1101/005702
Nicholas C. Wu
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
2Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
7 These authors contributed equally to this work
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Arthur P. Young
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
7 These authors contributed equally to this work
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Laith Q. Al-Mawsawi
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Anders C. Olson
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Jun Feng
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Hangfei Qi
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Shu-Hwa Chen
3Institute of Information Science, Academia Sinica, Taipei, Taiwan
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I-Hsuan Lu
3Institute of Information Science, Academia Sinica, Taipei, Taiwan
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Chung-Yen Lin
3Institute of Information Science, Academia Sinica, Taipei, Taiwan
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Robert G. Chin
4Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Harding H. Luan
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Nguyen Nguyen
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Stanley F. Nelson
2Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
4Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Xinmin Li
5Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Ting-Ting Wu
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Ren Sun
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
2Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
6AIDS Institute, University of California, Los Angeles, CA 90095, USA
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 31, 2014.
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High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution
Nicholas C. Wu, Arthur P. Young, Laith Q. Al-Mawsawi, Anders C. Olson, Jun Feng, Hangfei Qi, Shu-Hwa Chen, I-Hsuan Lu, Chung-Yen Lin, Robert G. Chin, Harding H. Luan, Nguyen Nguyen, Stanley F. Nelson, Xinmin Li, Ting-Ting Wu, Ren Sun
bioRxiv 005702; doi: https://doi.org/10.1101/005702
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High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution
Nicholas C. Wu, Arthur P. Young, Laith Q. Al-Mawsawi, Anders C. Olson, Jun Feng, Hangfei Qi, Shu-Hwa Chen, I-Hsuan Lu, Chung-Yen Lin, Robert G. Chin, Harding H. Luan, Nguyen Nguyen, Stanley F. Nelson, Xinmin Li, Ting-Ting Wu, Ren Sun
bioRxiv 005702; doi: https://doi.org/10.1101/005702

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