Evidence map›Paper›PMID 36640354›Full record

ArticleCell reports2023

Mutational fitness landscape of human influenza H3N2 neuraminidase.

Ruipeng Lei, Andrea Hernandez Garcia, Timothy J C Tan, Qi Wen Teo, Yiquan Wang, Xiwen Zhang, Shitong Luo, Satish K Nair, Jian Peng, Nicholas C Wu

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Ruipeng LeiDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Andrea Hernandez GarciaDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Timothy J C TanCenter for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Qi Wen TeoDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Yiquan WangDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Xiwen ZhangHeliXon Limited, Beijing 100084, China.
Shitong LuoHeliXon Limited, Beijing 100084, China.
Satish K NairDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Jian PengHeliXon Limited, Beijing 100084, China; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: jianpeng@illinois.edu.
Nicholas C WuDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: nicwu@illinois.edu.
University of Illinois Urbana-Champaign · US

Funding

Biophysical constraints of influenza neuraminidase evolutionR01AI165475 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI WU, NICHOLAS C. · 2022 to 2025
$2.0M
NIAID NIH HHS R01 AI165475
6 · The paper itself

Abstract

Influenza neuraminidase (NA) has received increasing attention as an effective vaccine target. However, its mutational tolerance is not well characterized. Here, the fitness effects of >6,000 mutations in human H3N2 NA are probed using deep mutational scanning. Our result shows that while its antigenic regions have high mutational tolerance, there are solvent-exposed regions with low mutational tolerance. We also find that protein stability is a major determinant of NA mutational fitness. The deep mutational scanning result correlates well with mutational fitness inferred from natural sequences using a protein language model, substantiating the relevance of our findings to the natural evolution of circulating strains. Additional analysis further suggests that human H3N2 NA is far from running out of mutations despite already evolving for >50 years. Overall, this study advances our understanding of the evolutionary potential of NA and the underlying biophysical constraints, which in turn provide insights into NA-based vaccine design.

Indexed as

Influenza, HumanEvolution, MolecularHumansInfluenza A Virus, H3N2 SubtypeMutationNeuraminidaseNeuraminidaseCP: Molecular biologydeep mutational scanningevolutioninfluenzaneuraminidaseprotein language modelprotein stabilityprotein structure

Identifiers

PMID36640354
PMCPMC9931530
OpenAlexW4313554770

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.