Supplementary Dataset 1: RF index for each mutation. (XLS 364 kb

A Gulyás-Kovács

A Okada

A Shishkov

A Özen

AD Kelleher

Arthur P. Young

AS Taft

AV Shishkov

C Kuiken

C Wang

CA Olson

D de Juan

D Elton

D Melamed

DI Lou

DL Chao

DM Fowler

DM Weinreich

DP Nayak

EA Govorkova

EC Hutchinson

FG Hayden

G Neumann

GI Lang

H Qi

J Lohmeyer

Janice M. Yoshizawa

JD Bloom

Jian Zhou

JR Schnell

KM Bialas

L Hakes

LH Pinto

LI Gong

Ling Dong

LQ Al-Mawsawi

M Lunzer

M Nijhuis

M Terajima

MA Fares

MB Doud

ML Grantham

MZ Tien

NC Wu

Nicholas C. Wu

NSHN Moorthy

P Gómez-Puertas

P Venkataraman

PC Roberts

R Chen

R Sanjun

RB Squires

RD Antrobus

Ren Sun

S Arzt

S Chakrabarti

S Kryazhimskiy

S Trindade

SA Wharton

Shuai Le

Tian-Hao Zhang

Ting-Ting Wu

W Kabsch

Xinmin Li

Y Bao

Y Tang

YM Zhang

YT Lee

Yuanyuan Wang

Yushen Du

Z Li

BMC Genomics

PubMed

Nicholas Wu (2980818)

Yushen Du (549945)

Shuai Le (412109)

Arthur Young (3411365)

Tian-Hao Zhang (624388)

Yuanyuan Wang (20181)

Jian Zhou (28020)

Janice Yoshizawa (823098)

Ling Dong (470979)

Xinmin Li (2873864)

Ting-Ting Wu (1693231)

Ren Sun (82856)

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Additional file 1 of Coupling high-throughput genetics with phylogenetic information reveals an epistatic interaction on the influenza A virus M segment

BackgroundEpistasis is one of the central themes in viral evolution due to its importance in drug resistance, immune escape, and interspecies transmission. However, there is a lack of experimental approach to systematically probe for epistatic residues.ResultsBy utilizing the information from natural occurring sequences and high-throughput genetics, this study established a novel strategy to identify epistatic residues. The rationale is that a substitution that is deleterious in one strain may be prevalent in nature due to the presence of a naturally occurring compensatory substitution. Here, high-throughput genetics was applied to influenza A virus M segment to systematically identify deleterious substitutions. Comparison with natural sequence variation showed that a deleterious substitution M1 Q214H was prevalent in circulating strains. A coevolution analysis was then performed and indicated that M1 residues 121, 207, 209, and 214 naturally coevolved as a group. Subsequently, we experimentally validated that M1 A209T was a compensatory substitution for M1 Q214H.ConclusionsThis work provided a proof-of-concept to identify epistatic residues by coupling high-throughput genetics with phylogenetic information. In particular, we were able to identify an epistatic interaction between M1 substitutions A209T and Q214H. This analytic strategy can potentially be adapted to study any protein of interest, provided that the information on natural sequence variants is available

Wu, Nicholas C

Du, Yushen

Le, Shuai

Young, Arthur P

Zhang, Tian-Hao

Wang, Yuanyuan

Zhou, Jian

Yoshizawa, Janice M

Dong, Ling

Li, Xinmin

Wu, Ting-Ting

Sun, Ren

eScholarship - University of California

English

Coupling high-throughput genetics with phylogenetic information reveals an epistatic interaction on the influenza A virus M segment

Crossref

https://figshare.com/articles/Additional_file_1_of_Coupling_high-throughput_genetics_with_phylogenetic_information_reveals_an_epistatic_interaction_on_the_influenza_A_virus_M_segment/4325603

Additional file 1 of Coupling high-throughput genetics with phylogenetic information reveals an epistatic interaction on the influenza A virus M segment

Abstract

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eScholarship - University of California

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